Outcome of patients with different stages of acute-on-chronic liver failure treated with artificial liver support system.

Background: Elevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail. Methods: A previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR < 1.5 (Pre-stage), 1.5 ≤ PT-INR < 2.0 (Early-stage), 2.0 ≤ PT-INR < 2.5 (Mid-stage), and PT-INR ≥ 2.5 (End-stage). The Cox proportional hazards models were used to estimate the association between stages of ACLF or sessions of ALSS treatment and 90 day mortality. Results: A total of 301 ACLF patients were enrolled. The 90 day mortality risk of Early-stage ACLF patients (adjusted hazard ratio (aHR) (95% confidence interval (CI)), 3.20 (1.15-8.89), p = 0.026), Mid-stage ACLF patients (3.68 (1.34-10.12), p = 0.011), and End-stage ACLF patients (12.74 (4.52-35.91), p < 0.001) were higher than that of Pre-stage ACLF patients, respectively. The 90 day mortality risk of Mid-stage ACLF patients was similar to that of Early-stage ACLF patients (1.15 (0.69-1.94), p = 0.591). The sessions of ALSS treatment was an independent protective factor (aHR (95% CI), 0.81 (0.73-0.90), p < 0.001). The 90 day mortality risk in ACLF patients received 3-5 sessions of ALSS treatment was lower than that of patients received 1-2 sessions (aHR (95% CI), 0.34 (0.20-0.60), p < 0.001), whereas the risk in patients received ≥6 sessions of ALSS treatment was similar to that of patients received 3-5 sessions (0.69 (0.43-1.11), p = 0.128). Conclusion: ACLF patients in Pre-, Early-, and Mid-stages might be more eligible for ALSS treatment. Application of 3-5 sessions of ALSS treatment might be reasonable.

TRIM25-mediated XRCC1 ubiquitination accelerates atherosclerosis by inducing macrophage M1 polarization and programmed death.

BACKGROUND: Macrophage-mediated cleaning up of dead cells is a crucial determinant in reducing coronary artery inflammation and maintaining vascular homeostasis. However, this process also leads to programmed death of macrophages. So far, the role of macrophage death in the progression of atherosclerosis remains controversial. Also, the underlying mechanism by which transcriptional regulation and reprogramming triggered by macrophage death pathways lead to changes in vascular inflammation and remodeling are still largely unknown. TRIM25-mediated RIG-I signaling plays a key role in regulation of macrophages fate, however the role of TRIM25 in macrophage death-mediated atherosclerotic progression remains unclear. This study aims to investigate the relationship between TRIM25 and macrophage death in atherosclerosis. METHODS: A total of 34 blood samples of patients with coronary stent implantation, including chronic total occlusion (CTO) leisions (n = 14) or with more than 50% stenosis of a coronary artery but without CTO leisions (n = 20), were collected, and the serum level of TRIM25 was detected by ELISA. Apoe-/- mice with or without TRIM25 gene deletion were fed with the high-fat diet (HFD) for 12 weeks and the plaque areas, necrotic core size, aortic fibrosis and inflammation were investigated. TRIM25 wild-type and deficient macrophages were isolated, cultured and stimulated with ox-LDL, RNA-seq, real-time PCR, western blot and FACS experiments were used to screen and validate signaling pathways caused by TRIM25 deletion. RESULTS: Downregulation of TRIM25 was observed in circulating blood of CTO patients and also in HFD-induced mouse aortas. After HFD for 12 weeks, TRIM25-/-ApoeE-/- mice developed smaller atherosclerotic plaques, less inflammation, lower collagen content and aortic fibrosis compared with TRIM25+/+ApoeE-/- mice. By RNA-seq and KEGG enrichment analysis, we revealed that deletion of TRIM25 mainly affected pyroptosis and necroptosis pathways in ox-LDL-induced macrophages, and the expressions of PARP1 and RIPK3, were significantly decreased in TRIM25 deficient macrophages. Overexpression of TRIM25 promoted M1 polarization and necroptosis of macrophages, while inhibition of PARP1 reversed this process. Further, we observed that XRCC1, a repairer of DNA damage, was significantly upregulated in TRIM25 deficient macrophages, inhibiting PARP1 activity and PARP1-mediated pro-inflammatory change, M1 polarization and necroptosis of macrophages. By contrast, TRIM25 overexpression mediated ubiquitination of XRCC1, and the inhibition of XRCC1 released PARP1, and activated macrophage M1 polarization and necroptosis, which accelerated aortic inflammation and atherosclerotic plaque progression. CONCLUSIONS: Our study has uncovered a crucial role of the TRIM25-XRCC1Ub-PARP1-RIPK3 axis in regulating macrophage death during atherosclerosis, and we highlight the potential therapeutic significance of macrophage reprogramming regulation in preventing the development of atherosclerosis.

Synthesis and Characterization of 2D Ternary Compound TMD Materials Ta3VSe8.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) are garnering considerable scientific interest, prompting discussion regarding their prospective applications in the fields of nanoelectronics and spintronics while also fueling groundbreaking discoveries in phenomena such as the fractional quantum anomalous Hall effect (FQAHE) and exciton dynamics. The abundance of binary compound TMDs, such as MX2 (M = Mo, W; X = S, Se, Te), has unlocked myriad avenues of exploration. However, the exploration of ternary compound TMDs remains relatively limited, with notable examples being Ta2NiS5 and Ta2NiSe5. In this study, we report the synthesis of a new 2D ternary compound TMD materials, Ta3VSe8, employing the chemical vapor transport (CVT) method. The as-grown bulk crystal is shiny and can be easily exfoliated. The crystal quality and structure are verified by X-ray diffraction (XRD), while the surface morphology, stoichiometric ratio, and uniformity are determined by scanning electron microscopy (SEM). Although the phonon property is found stable at different temperatures, magneto-resistivity evolves. These findings provide a possible approach for the realization and exploration of ternary compound TMDs.

Efficacy of an mHealth App to Support Patients' Self-Management of Hypertension: Randomized Controlled Trial.

BACKGROUND: Hypertension is a significant global disease burden. Mobile health (mHealth) offers a promising means to provide patients with hypertension with easy access to health care services. Yet, its efficacy needs to be validated, especially in lower-income areas with a high-salt diet. OBJECTIVE: This study aims to assess the efficacy of an mHealth app-based intervention in supporting patients' self-management of hypertension. METHODS: A 2-arm randomized controlled trial was conducted among 297 patients with hypertension at the General Hospital of Ningxia Medical University, Ningxia Hui Autonomous Region, China. Participants selected via convenience sampling were randomly allocated into intervention and control groups. Intervention group participants were trained and asked to use an mHealth app named Blood Pressure Assistant for 6 months. They could use the app to record and upload vital signs, access educational materials, and receive self-management reminders and feedback from health care providers based on the analysis of the uploaded data. Control group participants received usual care. Blood pressure (BP) and 2 questionnaire surveys about hypertension knowledge and lifestyle behavior were used to assess all participants at baseline and 6 months. Data analysis was performed with SPSS software using 2-tailed t tests and a chi-square test. RESULTS: There were no significant differences in baseline characteristics and medication use between the 2 groups (all P>.05). After 6 months, although both groups show a significant pre-post improvement (P<.001 each), the BP control rate (ie, the proportion of patients with a systolic BP of <140 mm Hg and diastolic BP of <90 mm Hg) in the intervention group was better than that in the control group (100/111, 90.1% vs 75/115, 65.2%; P<.001). The mean systolic and diastolic BP were significantly reduced by 25.83 (SD 8.99) and 14.28 (SD 3.74) mm Hg in the intervention group (P<.001) and by 21.83 (SD 6.86) and 8.87 (SD 4.22) mm Hg in the control group (P<.001), respectively. The differences in systolic and diastolic BP between the 2 groups were significant (P<.001 and P=.01, respectively). Hypertension knowledge significantly improved only in the intervention group in both pre-post and intergroup comparisons (both P<.001). However, only intragroup improvement was observed for lifestyle behaviors in the intervention group (P<.001), including medication adherence (P<.001), healthy diet (P=.02), low salt intake (P<.001), and physical exercises (P=.02), and no significant difference was observed in the control group or on intergroup comparisons. CONCLUSIONS: This research shows that the mHealth app-based intervention has the potential to improve patient health knowledge and support self-management among them toward a healthier lifestyle, including medication adherence, low-salt diets, and physical exercises, thereby achieving optimal BP control. Further research is still needed to verify the specific effects of these interventions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026437; https://www.chictr.org.cn/showproj.html?proj=38801.

Association of direct bilirubin to total bilirubin ratio with 90-day mortality in patients with acute-on-chronic liver failure.

Background: Hyperbilirubinemia occurs when the liver fails to process bilirubin properly. A disproportionate increase in direct bilirubin indicates a decreased ability of the hepatocytes to uptake and/or convert bilirubin, which may impact the prognosis of patients with acute-on-chronic liver failure (ACLF). However, the association of direct bilirubin to total bilirubin ratio (DB/TB) with outcomes in patients with ACLF remains unclear. Methods: A retrospective study was conducted in West China Hospital of Sichuan University to assess the association between DB/TB and 90-day mortality in patients with ACLF. The diagnosis of ACLF was based on the Chinese Group on the Study of Severe Hepatitis B (COSSH) ACLF criteria. Ordinal logistic regression models, linear regression models, and Cox proportional hazards models were applied to evaluate the association between DB/TB and hepatic encephalopathy, disease severity, and outcome, respectively. Results: A total of 258 patients with ACLF were included. The surviving patients were less likely to have liver cirrhosis and comorbidities, and their disease severities were milder than the dead. DB/TB was negatively correlated to cerebral score for hepatic encephalopathy (adjusted odds ratio: 0.01, p = 0.043), and disease severity (adjusted standardized coefficients: -0.42~-0.31, all p < 0.001), respectively. A significant 90-day mortality risk of DB/TB was observed [all adjusted hazard ratio (aHR) < 0.20 and all p ≤ 0.001]. Compared with patients with DB/TB < 0.80, patients with ACLF and DB/TB ≥ 0.80 had much lower 90-day mortality risk (all aHR < 0.75 and all p < 0.01). Conclusion: DB/TB could be an independent risk factor to predict the short-term prognosis in patients with ACLF. More attention should be paid to patients with lower DB/TB due to their poorer prognosis and more urgent need for liver transplantation.Clinical trial registration:http://www.chictr.org.cn/showproj.aspx?proj=56960, identifier, ChiCTR2000035013.

Exploring indicators of success in chronic total occlusion percutaneous coronary intervention with Stingray system-based antegrade dissection re-entry: Insights from retrospective analysis.

BACKGROUND: The predictors of success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) through antegrade dissection and re-entry (ADR) using the Stingray system (Stingray ADR) remain elusive, mainly owing to the lack of consecutive angiographic and procedural records of patients. OBJECTIVES: This study aimed to identify indicators that can determine the success of CTO PCI performed using the Stingray ADR technique. METHODS: The clinical data of 115 patients who underwent CTO PCI through Stingray ADR at the same cardiac center were retrospectively and consecutively collected. Multivariate logistic regression analysis was performed to investigate the indicators of the success of ADR attempts. RESULTS: The technical success rate of Stingray ADR in CTO PCI was 72.2%. The overall technical success rate of CTO recanalization was 78.3% in all CTO PCIs having used Stingray Low Profile balloon. Vessel calcification (odds ratio [OR]: 4.03; 95% confidence interval [CI]: 1.49-11.88; p = 0.008), and retrograde puncture indicator (OR: 4.89; 95% CI: 1.51-17.11; p = 0.009) were identified as independent positive predictors. Blunt/no stump proximal to the occlusion segment (OR: 0.22; 95% CI: 0.06-0.64; p = 0.009), decision time before Stingray ADR (per 1 h increase) (OR: 0.54; 95% CI: 0.31-0.92; p = 0.026), operation duration of Stingray ADR (per 10 min increase) (OR: 0.62; 95% CI: 0.40-0.94; p = 0.028), and puncture site at the intraplaque region (OR: 0.24; 95% CI: 0.06-0.84; p = 0.026) were identified as the four negative independent predictors. CONCLUSIONS: This study revealed independent predictors of the success of CTO PCI performed using the Stingray ADR technique. As for CTO characteristics, the presence of calcification in the CTO segment and a tapered stump proximal to the lesion site can facilitate successful Stingray ADR. As for the procedures, the success rate of Stingray ADR can be improved by initiating the technique decisively and promptly, operating the system quickly and accurately and creating a puncture in the distal cap region of CTO under retrograde guidance.

A Novel Parallel Wire-based Antegrade Dissection Re-entry Technique for Failed Retrograde Attempt of Coronary Chronic Total Occlusions with Risk Nomogram Analysis.

BACKGROUND: Rapid development in coronary chronic total occlusion (CTO) interventional techniques and devices have achieved a greater success rate with favorable outcomes. Antegrade dissection re-entry (ADR) technique is an important CTO crossing strategy and a desirable approach for long CTOs with good distal landing zone. However, unsuccessful procedures in contemporary CTO-percutaneous coronary intervention (PCI) remain, especially in lesions with non-interventional collaterals. METHOD: Based on a single center experience, a hybrid interventional algorithm, parallel wire-based ADR (PW-ADR) combines the advantages of parallel wire technique (PWT) and device-based ADR to target CTO lesions with failed retrograde approach. A retrospective analysis of patients who underwent PW-ADR was performed. A risk nomogram was created to identify patients at high risk for technical failure. RESULTS: A total of 57 patients treated with PW-ADR were ultimately included in the present study. A total of 46 (80.7%) cases achieved technical success and procedural success, with low incidence of in-hospital complications or 1-year major adverse cardiac events (MACE). The risk nomogram identified 3 predictor variables associated with technical failure of PW-ADR, including tortuous vessel, J-CTO score, and times of antegrade coronary angiography (CAG) during ADR, with promising accuracy (AUROC 0.947). CONCLUSION: The novel hybrid CTO-PCI algorithm, PW-ADR, provided an alternative interventional approach for complex CTO lesions with a promising success rate. The risk nomogram served as a prompter for high-risk cases, which may warrant a change in treatment strategy.

The present study reported a new hybrid-PCI strategy with a promising success rate for the treatment of CTO from a single center experience, over last 5 years. A retrospective analysis of patients who underwent PW-ADR was performed. A risk nomogram was created to identify patients at high risk for technical failure. 80.7% of patients treated with PW-ADR were achieved technical success and procedural success, with low incidence of in-hospital complications or 1-year MACE in the present study. A total of 3 predictor variables were identified to be associated with technical failure of PW-ADR, including tortuous vessel, J-CTO score, and times of antegrade CAG during ADR. This prediction tool may allow early identification of more complex and difficult CTO cases that require a timely switch in strategic approach or termination of the procedure to avoid unnecessary surgical risk.

Epigenetically altered macrophages promote development of diabetes-associated atherosclerosis.

Background: Atherosclerosis (AS) risk is elevated in diabetic patients, but the underlying mechanism such as involvement of epigenetic control of foam macrophages remains unclear. We have previously shown the importance of immune regulation on endothelial cells to AS development in diabetes. In this study, we examined the hypothesis that diabetes may promote AS through modification of the epigenetic status of macrophages. Methods: We employed the Laser Capture Microdissection (LCM) method to evaluate the expression levels of key epigenetic regulators in both endothelial cells and macrophages at the AS lesions of patients. We then assessed the correlation between the significantly altered epigenetic regulator and serum levels of low-density Lipoprotein (LDL), triglycerides (TRIG) and high-density Lipoprotein (HDL) in patients. In vitro, the effects of high glucose on glucose utilization, lactate production, succinate levels, oxygen consumption and polarization in either undifferentiated or differentiated bone marrow-derived macrophages (BMDMs) were analyzed. The effects of depleting this significantly altered epigenetic regulator in macrophages on AS development were assessed in AS-prone diabetic mice. Results: Histone deacetylase 3 (HDAC3) was identified as the most significantly altered epigenetic regulator in macrophages from the AS lesions in human diabetic patients. The levels of HDAC3 positively correlated with high serum LDL and TRIG, as well as low serum HDL. High glucose significantly increased glucose utilization, lactate production, succinate levels and oxygen consumption in cultured macrophages, and induced proinflammatory M1-like polarization. Macrophage depletion of HDAC3 significantly attenuated AS severity in AS-prone diabetic mice. Conclusion: Epigenetically altered macrophages promote development of diabetes-associated AS, which could be prevented through HDAC3 depletion.

Giant Superlinear Power Dependence of Photocurrent Based on Layered Ta2 NiS5 Photodetector.

Photodetector based on two-dimensional (2D) materials is an ongoing quest in optoelectronics. 2D photodetectors are generally efficient at low illuminating power but suffer severe recombination processes at high power, which results in the sublinear power-dependent photoresponse and lower optoelectronic efficiency. The desirable superlinear photocurrent is mostly achieved by sophisticated 2D heterostructures or device arrays, while 2D materials rarely show intrinsic superlinear photoresponse. This work reports the giant superlinear power dependence of photocurrent based on multilayer Ta2 NiS5 . While the fabricated photodetector exhibits good sensitivity (3.1 mS W-1 per □) and fast photoresponse (31 µs), the bias-, polarization-, and spatial-resolved measurements point to an intrinsic photoconductive mechanism. By increasing the incident power density from 1.5 to 200 µW µm-2 , the photocurrent power dependence varies from sublinear to superlinear. At higher illuminating conditions, prominent superlinearity is observed with a giant power exponent of γ = 1.5. The unusual photoresponse can be explained by a two-recombination-center model where density of states of the recombination centers (RC) effectively closes all recombination channels. The photodetector is integrated into camera for taking photos with enhanced contrast due to superlinearity. This work provides an effective route to enable higher optoelectronic efficiency at extreme conditions.

A novel tapered guide extension catheter facilitated successful completion of complex percutaneous coronary intervention.

BACKGROUND: Guide extension catheters (GEC) are widely applied to cope with insufficient backup support in complex percutaneous coronary intervention (PCI). In the study, we aim to evaluate the feasibility and safety with a novel 5-4F tapered GEC used in complex lesion. METHODS: The single-center retrospective study enrolled a total of 615 patients, in whom the 5F or 5-4F Expressman GEC was used to facilitate PCI procedure. Demographic and procedural data were collected. RESULTS: 5F GEC was used in 295 patients and 5-4F tapered GEC in 320 patients. The average age was 63.6 ± 11.0 years and 81.6% of the patients were male. Severe calcification and chronic total occlusion (CTO) were the commonest indication for the GEC use. The 5-4F tapered GEC was frequently used in active greeting technique (AGT) during CTO intervention procedure than 5F GEC (6.1% vs. 13.1%, p < 0.001). The average depth of intubation was 41.5 ± 19.6 mm for the 5-4F tapered GEC and 24.4 ± 15.1 mm for 5F GEC (p < 0.001). The rate of successful device delivery with 5-4F GEC was higher than 5F GEC (95.6% vs. 98.4%, p = 0.037). Pressure damping with 5F GEC occurred frequently than 5-4F GEC (7.4% vs. 2.5%, p < 0.05). Similarly, the incidence of intraoperative hypotension was higher in 5F GEC than 5-4F GEC (4.7% vs.1.9%, p < 0.05). CONCLUSIONS: The novel 5-4F tapered GEC was superior to the 5F GEC in facilitating successful completion of PCI in the majority of patients with complex lesions via transradial approach.

Treatment strategy for spontaneous coronary artery dissection based on anatomical characteristics.

OBJECTIVES: To compare the clinical and angiographic characteristics of high-risk and low-risk spontaneous coronary artery dissection (SCAD) patients to determine the optimal treatment strategy. BACKGROUND: SCAD is a rare and emerging cause of acute coronary syndrome and sudden cardiac death, especially in young female patients. However, the indication of percutaneous coronary intervention (PCI) in patients with SCAD remains elusive. METHODS: We evaluated the clinical and angiographic characteristics of all SCAD patients admitted to our center from 2012 to 2020. The outcomes of the high-risk and low-risk SCAD patients according to the location of the lesion segment with dissection or intramural hematoma were compared. Further analyses were performed to evaluate the vessel healing or residual dissection in the patients receiving the follow-up angiography. RESULTS: A total of 81 SCAD patients were enrolled in the present study, in which 38 patients were categorized as high-risk group, defined as involvement of the left main artery or proximal segment of any main coronary artery. PCI was the more common treatment approach in the high-risk group (68.4%), while conservative treatment was more common in the low-risk group (62.8%). The incidence of major adverse cardiac events, defined as cardiac death, myocardial infarction, unstable angina pectoris, severe arrhythmias, or heat failure, within 1 year follow-up was similar between the two groups. 57 patients (70.4%) received the follow-up angiography after 1 year. The high- and low-risk groups had a similar rate of vessel healing among the PCI treatment patients. However, more patients achieved spontaneous healing in the low-risk group than the high-risk group among the conservative treatment patients (86.4% vs. 33.3%, p < 0.05). CONCLUSIONS: Conservative management remains the recommended treatment strategy for the low-risk SCAD patients. PCI could be considered in high-risk SCAD patients with favorable clinical outcomes and vessel healing. Characterization of lesion anatomy may be an important indicator for treatment decision.

Atorvastatin-induced tolerogenic dendritic cells improve cardiac remodeling by suppressing TLR-4/NF-κB activation after myocardial infarction.

OBJECTIVE: Myocardial infarction (MI) caused by ischemic cardiomyocyte necrosis induces inflammatory responses that strongly affect ventricular remodeling. Tolerogenic dendritic cells (tDCs) can suppress this effect on inflammatory responses. However, the precise role of atorvastatin-induced tDCs in ventricular remodeling after MI remains unclear. METHODS: To explore the effect of necrotic cardiomyocytes (SNC) and/or atorvastatin on DC function, the expression of CD40, CD80, CD86, and MHC-II was determined using flow cytometry. The protein levels of TLR-4/NF-κB-related molecules were evaluated using western blotting. The infarct area after MI was determined via 2,3,5-triphenyltetrazolium chloride staining. The TUNEL assay was employed to evaluate the apoptosis of cardiomyocytes in heart sections. Masson's trichrome method was used to determine the extent of fibrosis. RESULTS: Compared to the DCs co-cultured with PBS (control), cells co-cultured with Supernatant-IM or Supernatant-NH produced higher levels of inflammatory cytokines, including TNF-α, IL-1, IL-6, IL-12P40, and IL-8. This cytokine production was impaired by atorvastatin treatment. SNC treatment induced DC maturation and enhanced inflammatory cytokine secretion and oxidative stress through TLR-4/NF-κB pathway activation. Compared to that in the PBS-treated group, the left ventricular ejection fraction was significantly improved after tDC treatment. Additionally, compared to that in the PBS-treated group, tDC treatment reduced the left ventricular end-diastolic and end-systolic diameters in mice. Furthermore, treatment with tDCs improved the left ventricular systolic function, attenuated inflammatory cell infiltration, and reduced cardiomyocyte apoptosis, myocardial fibrosis, and infarct size compared to those in the control group. CONCLUSIONS: Adoptive transfer of atorvastatin-induced tDCs alleviated post-infarction cardiomyocyte apoptosis and myocardial fibrosis in association with decreased inflammatory cell infiltration and inhibited oxidative stress, likely by suppressing TLR-4/NF-κB activation after myocardial infarction.

Topological Lifshitz transition and one-dimensional Weyl mode in HfTe5.

Landau band crossings typically stem from the intra-band evolution of electronic states in magnetic fields and enhance the interaction effect in their vicinity. Here in the extreme quantum limit of topological insulator HfTe5, we report the observation of a topological Lifshitz transition from inter-band Landau level crossings using magneto-infrared spectroscopy. By tracking the Landau level transitions, we demonstrate that band inversion drives the zeroth Landau bands to cross with each other after 4.5 T and forms a one-dimensional Weyl mode with the fundamental gap persistently closed. The unusual reduction of the zeroth Landau level transition activity suggests a topological Lifshitz transition at 21 T, which shifts the Weyl mode close to the Fermi level. As a result, a broad and asymmetric absorption feature emerges due to the Pauli blocking effect in one dimension, along with a distinctive negative magneto-resistivity. Our results provide a strategy for realizing one-dimensional Weyl quasiparticles in bulk crystals.

Comparing albuvirtide plus ritonavir-boosted lopinavir regimen to two nucleotide reverse transcriptase inhibitors plus ritonavir-boosted lopinavir in HIV-infected individuals who failed initial treatment: a retrospective comparative cohort study.

Background: Albuvirtide (ABT), a fusion inhibitor against human immunodeficiency virus (HIV) infection, has good efficacy and tolerability for HIV treatment. However, there is a paucity of data regarding ABT-based regimen as second-line therapy. This current study evaluated the efficacy and safety of switching to ABT + ritonavir-boosted lopinavir (LPV/r) treatment in a cohort of HIV-infected individuals who failed initial treatment. Methods: This retrospective comparative cohort study included patients who failed initial treatment and switched to either ABT + LPV/r (the ABT group) or two nucleotide reverse transcriptase inhibitors (NRTIs) + LPV/r (the NRTI group) between November 2019 and December 2020 in the People's Hospital of Zhaojue County in Liangshan Yi Autonomous Prefecture, China. All individuals were followed up from baseline to 12 weeks after conversion, or until the patient developed unacceptable toxic effects or was loss of follow-up. The proportion of patients who achieved virological suppression (viral load <50 copies/mL) at week 12 was considered a primary efficacy endpoint. Safety outcomes included the incidence of adverse events and laboratory abnormalities. All participants underwent resistance testing before regimen conversion. The linear regression model was applied to evaluate the association of CD4+ T cell count with the patient's clinical characteristics. Results: A total of 71 patients were included in this study, the two groups were comparable at baseline in terms of age, sex, CD4+ T cell count, and viral load. The suppression of HIV-1 RNA to levels <50 copies/mL was achieved in 82.4% (28/31) and 29.7% (11/34) of patients in the ABT group and the NRTI group, respectively (P<0.001). Older age (P=0.016) and higher alkaline phosphatase (ALP) levels (P=0.038), but not rescue regimen, were associated with attenuated CD4+ T cell recovery. Most adverse events mild in severity, with abdominal pain as the most reported event in two groups (26.8%, 19/71), and no severe adverse events were detected. Conclusions: Conversion to ABT + LPV/r therapy appears to be an effective and safe strategy. This treatment regimen has great potential to be generalized in the HIV-infected population, although further testing in a larger patient population is required to verify these results.

The Value of Metagenomic Next-Generation Sequencing in Leishmaniasis Diagnosis: A Case Series and Literature Review.

Background: Leishmaniasis is a zoonotic disease caused by Leishmania spp. and spreads through sandfly bites. Owing to the wide range of nonspecific clinical symptoms, patients with leishmaniasis are frequently misdiagnosed or underdiagnosed. Methods: The study participants were 7 metagenomic next-generation sequencing (mNGS)-diagnosed patients with leishmaniasis who could not be diagnosed using conventional methods. Clinical data were retrospectively collected and analyzed. When searching PubMed for mNGS and leishmaniasis, 8 peer-reviewed case reports in English were retrieved. Results: A total of 7 patients with recurrent fever, pancytopenia, and significant splenomegaly were included in this study. Only 3 individuals tested positive for rK39. Two individuals, 1 of whom was HIV-positive, had Leishmania amastigotes identified in their bone marrow. However, all patients' blood mNGS findings pointed to Leishmania infection, and they were finally diagnosed with leishmaniasis. Sodium stibogluconate therapy with a short course of amphotericin B was administered to all patients. The prognosis for the remaining patients was good, except for 1 who died of multiple organ failure. Conclusions: mNGS could be used to identify leishmaniasis, particularly in patients who are difficult to diagnose using conventional approaches.

[Assessment Value of Short-Term Prognosis of Six Predictive Models for Patients with Acute-on-Chronic Liver Failure Treated with Artificial Liver Support System].

Objective: To apply 6 predictive models on acute-on-chronic liver failure (ACLF) patients treated with artificial liver support system (ALSS), and to compare their assessment values for the short-term prognosis of patients. Methods: A total of 258 ACLF patients who underwent ALSS therapy between January 2018 and December 2019 were selected from the ALSS clinical database established by West China Hospital, Sichuan University, and their clinical data and 90-day prognosis information were collected. Cox proportional hazards model was used to estimate the association between the six predictive models, including Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH ACLF), European Association for the Study of the Liver--Chronic Liver Failure-Consortium (CLIF-C) ACLF, CLIF-C Organ Failure (OF), Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) ACLF, Model for End-Stage Liver Disease (MELD) and Simplified MELD (sMELD), and 90-day mortality, which included death or receiving liver transplantation. The area under the receiver operating characteristic (ROC) curve ( AUC), Harrell's C-index and Brier scores were calculated and compared to evaluate the predictive power. Results: A total of 258 ACLF patients were enrolled. Of these patients, who had a mean age of (46.2±11.7) years old, 37 (14.3%) patients were female, 202 (78.3%) patients had a diagnosis of liver cirrhosis, and 107 (41.5%) patients died during the 90-day follow-up period. The six predictive models all yielded higher scores for patients who died than those for patients who survived (all P<0.001). The six predictive models were all independent risk factors for the short-term prognosis of ACLF patients treated with ALSS (all adjusted hazard ratio [HR]>1, all P<0.001). The AUC (0.806, 95% confidence interval [CI]: 0.753-0.853) and Harrell's C-index (0.772, 95% CI: 0.727-0.816) of COSSH ACLF were much higher than those of the five other predictive models (all AUCs<0.750, P<0.01; all Harrell's C-indices<0.750, P<0.001). The Brier score of COSSH ACLF was 0.18 (95% CI: 0.15-0.20). The 90-day mortality of patients defined as having low risk, moderate risk, and high risk according to the risk stratification of COSSH ACLF were 22.2%, 56.3%, and 90.2%, respectively. Conclusion: The COSSH ACLF could more accurately predict short-term prognosis in ACLF patients who received ALSS therapy, and could facilitate clinical decision-making.

Impact of intracoronary reteplase during primary percutaneous coronary intervention on infarct size in large anterior myocardial infarction: rationale and design of the RECOVER II trial.

Background: Thrombus embolization and microvascular obstruction during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is commonly detected, which causes inadequate myocardial perfusion and elevated infarct size. An approach with low-dose intracoronary fibrinolytic treatment for reducing distal embolization and improving myocardial reperfusion in high-risk STEMI cases remains controversial. Methods: The RECOVER II study represents a multicenter, randomized, double-blind, parallel-group trial assessing low-dose adjunctive intracoronary reteplase during primary PCI in individuals with large anterior myocardial infarction and thrombus determined by angiography. The trial will enroll 306 cases who present within 12 h following STEMI for proximal or mid left anterior descending artery occlusion undergoing primary PCI. Cases will be randomized to receive a bolus intracoronary reteplase at 9 mg or 18 mg vs. placebo. The drug will be delivered over 2 minutes proximal to culprit lesions with an intracoronary catheter early after wire-crossing and before thrombus aspiration or balloon dilation. Results: The primary outcome will be infarct size assessed by late gadolinium-enhanced magnetic resonance imaging (MRI) (% of left ventricular mass) on day 7 after enrollment. Secondary outcomes will include the amount of microvascular obstruction and myocardial salvage index examined via MRI on day 7, angiographic measures of reperfusion [Thrombolysis in Myocardial Infarction (TIMI) coronary flow grade, TIMI frames count and myocardial blush grade], incidence of complete ST-segment resolution at 2 hours after reperfusion, area under the curve for troponin T, and rates of major adverse cardiovascular events at 30 days. Conclusions: RECOVER II will determine whether the addition of low-dose intracoronary reteplase early after wire-crossing as an adjunct to reperfusion treatment reduces infarct size in individuals with large anterior myocardial infarction. Trial Registration: ClinicalTrials.gov Identifier: NCT04571580.

[Drugs and hepatitis B virus reactivation].

Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the influence factors, as well as the early intervention measures. It is shown that multiple drugs, including chemotherapy drugs, immunotherapy drugs, directly acting antivirals, cell therapy, etc., can induce HBV-R by affecting host immunity or directly activating HBV transcription factors. HBV-R could cause severe liver damage, even interruption of treatment of original diseases, affecting the prognosis of patients. Through precisely identifying risk drugs, monitoring the influence factors, and prescribing preventive anti-HBV regimen if necessary, the incidence of HBV-R can be significantly reduced. It is also suggested that clinical physicians should not only pay attention to the early identification and intervention of HBV-R, but also further study the mechanism of HBV-R in depth, especially the underlying mechanism between host, HBV and risk factors. This will help to promote the discovery of more valuable markers for risk prediction and targets for early intervention, and to further reduce the risk of HBV-R and improve the prognosis of patients.

Impact of Subintimal Plaque Modification on Reattempted Chronic Total Occlusions Percutaneous Coronary Intervention.

BACKGROUND: Predictors of success in reattempted chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedures remain obscure, mainly owing to the lack of consecutive angiograms and procedural records of initial attempts in the same cohort. OBJECTIVES: This study sought to investigate the factors predicting the success of reattempted CTO PCI procedures. METHODS: A total of 208 consecutive patients who underwent a failed CTO PCI attempt and received reattempted procedure at the same cardiac center were retrospectively analyzed. Predictors of the success of reattempted procedures were evaluated. RESULTS: The overall technical success rate of reattempted CTO PCI procedures was 71.2%. Subintimal plaque modification (SPM) was implemented in 35 (16.8%) procedures in initial attempts. The reattempted technical success rate was 93.3% in cases in which SPM with guidewire (GW) crossing was achieved in the initial attempt; however, the success rate was 55.0% for procedures involving SPM without GW crossing. SPM with GW crossing (OR: 11.21; 95% CI: 1.31-96.16; P = 0.028), referral to high-volume operators (OR: 2.38; 95% CI: 1.14-4.98; P = 0.021), and a bidirectional approach (OR: 2.31; 95% CI: 1.12-4.79; P = 0.024) were positive independent predictors of technical success in the subsequent reattempt. The time interval for reattempt (per 90-day increment) was negatively correlated with the technical success of the reattempted procedures (OR: 0.85; 95% CI: 0.73-0.98; P = 0.030). CONCLUSIONS: This study identified independent predictors of success in reattempted CTO PCI procedures. SPM with GW crossing achieved in the initial attempt is associated with a higher success rate in the subsequent reattempt.

A randomized multicenter trial to evaluate early invasive strategy for patients with acute ST-segment elevation myocardial infarction presenting 24-48 hours from symptom onset: Protocol of the RESCUE-MI study.

BACKGROUND: For ST-segment elevation myocardial infarction (STEMI) patients presenting 24 to 48 hours from symptom onset, whether early invasive strategy should be performed still remains controversial. METHODS: This is a prospective, open-label, multicenter, investigator initiated, randomized controlled trial (NCT04962178) to evaluate the efficacy of early invasive strategy for STEMI patients within 24 to 48 hours of symptom onset. A total of 366 patients will be included from 10 hospitals in mainland China. They will be randomly (1:1) divided into 2 groups: the early invasive strategy group (primary percutaneous coronary intervention, PPCI) and conservative strategy group (optimal medical therapy with primary PCI not performed). All patients will be followed for 1 month. The primary end point is myocardial infarction size on cardiac magnetic resonance (CMR). The secondary end points are as follows: (1) major adverse cardiovascular events (MACE), which is defined as a composite of cardiac death, recurrent myocardial infarction, ischemic driven target vessel revascularization and stroke; (2) other CMR end points, including microvascular obstruction, intramyocardial hemorrhage, myocardial area at risk, left ventricular ejection fraction, left ventricular end diastolic volume and left ventricular end systolic volume. DISCUSSION: This study is designed to evaluate the efficacy of early invasive strategy for STEMI patients within 24 to 48 hours of symptom onset and will add more evidence for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04962178. Registered on July 14, 2021.