CMTM6 recruits T cells within the endocervical adenocarcinoma microenvironment and suppresses cell proliferation via the p53 pathway.

Endocervical adenocarcinoma (ECA), harboring poor prognosis, is divided into human papilloma virus (HPV)-associated adenocarcinoma (HPVA) and non-HPVA (NHPVA), each consisting of a heterogeneous immune microenvironment. We aim to examine the effect of CKLF-like MARVEL transmembrane domain 6 (CMTM6), a key regulator of PD-L1, on ECA. Immunohistochemistry and RNA-sequencing (RNA-seq) were used to detect CMTM6, Programmed death ligand 1 (PD-L1), and immune cells biomarkers levels in tumors. RT-qPCR and Western Blotting were used to detect the mRNA and protein level changed in cells. The expression of CMTM6 in ECA is upregulated compared to cervical squamous cell carcinoma tissues. More infiltrating T cells were observed in CMTM6high ECA tissues, especially in CMTM6high HPVA. Higher expression of CMTM6 is associated with a higher rate of infiltrating CD8+ T cells in HPVA, but not in NHPVA. ECA patients were divided into three groups according to the co-expression status of CMTM6 and PD-L1(CPS) . Patients with CMTM6high /PD-L1(CPS+) had the longest OS and DFS, especially in NHPVA patients. Moreover, knock down of CMTM6 promotes ECA cell proliferation via the p53 pathway. CMTM6 recruits T cells, suppresses ECA cell proliferation via the p53 pathway and can be used as a novel prognostic indicator for ECA patients.

Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV: A cross-sectional study.

We aimed to analyze the efficacy and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV (PLWH). A total of 143 PLWH and 50 healthy individuals were included in this study. A commercially available magnetic chemiluminescence enzyme immunoassay kit was used to detect serum IgG and IgM antibodies against SARS-CoV-2. Serum levels of SARS-CoV-2-specific IgG were significantly higher in the control group than in the PLWH group (p = 0.001). Overall, 76% of individuals in the control group were detected with seropositivity IgG against SARS-CoV-2 compared to 58% in the PLWH group (p = 0.024). In PLWH with IgG seropositivity, CD4+ T-cell counts before antiretroviral therapy (ART) was higher (p = 0.015). Multivariable analysis indicated that CD4+ T cells at IgG detection (odds ratio [OR] = 1.004, p = 0.006) and time after vaccination (OR = 0.977, p = 0.014) were independently associated with seropositivity IgG against SARS-CoV-2 in PLWH. Neutralizing antibody (nAb) titers in PLWH against wild-type SARS-CoV-2 were similar to those in the control group (p = 0.160). The proportion of seropositive nAbs against wild-type SARS-CoV-2 was also similar (95% in the control group vs. 97% in the PLWH group, p = 0.665). Similar results were obtained when nAb was detected against the delta variants with similar titers (p = 0.355) and a similar proportion of seropositive nAbs were observed (p = 0.588). All the side effects observed in our study were mild and self-limiting. The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in Chinese PLWH.

Association between hypertension and prognosis of patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: To investigate the association between hypertension and clinical outcomes, including in-hospital mortality, intensive care unit (ICU) admission, and invasive ventilation in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We implemented a systematic search of PubMed for articles that assessed clinical outcomes of hypertensive patients infected with SARS-CoV-2. The primary outcomes evaluated included: in-hospital mortality, ICU admission, and the use of invasive ventilation. RESULTS: A total of 18 studies were included, involving 13,293 patients and covering from January 25, 2020, to April 20, 2020. The relationship between hypertension and prognosis in COVID-19 patients was evaluated. Results showed that hypertension was a risk factor for in-hospital mortality in COVID-19 patients (RR: 2.20, 95% CI, 1.83-2.65, P < .001). Moreover, patients with hypertension were more likely to be admitted to ICU (RR: 1.86, 95% CI, 1.13-3.07, P = .001) and to use invasive ventilation (RR: 2.99, 95% CI, 1.73-5.17, P < .001). CONCLUSIONS: Among COVID-19 patients, those combined with hypertension had a significantly higher risk of in-hospital deaths, admission to ICU, and need for invasive ventilation.

Preoperative false-negative transthoracic echocardiographic results in native valve infective endocarditis patients: a retrospective study from 2001 to 2018.

BACKGROUND: Infective endocarditis (IE) is a lethal disease that is difficult to diagnosis early. Although echocardiography is one of the most widely used diagnostic technique, it has limited sensitivity. This study surveyed the clinical features of IE patients who underwent surgery and compared transthoracic echocardiography and histological findings to explore the factors related to false-negative echocardiographic results. METHODS: Medical records were extracted from IE patients consecutively hospitalized between June 2001 and June 2018. RESULTS: A total of 182 patients with native valve IE who underwent surgery were included. Compared to the non-surgery group, the surgery group was more likely to have pre-existing valvular lesions and more serious cardiac conditions and a relative lack of signs of infection and cerebrovascular events, leading to a lower proportion of "definite cases" before surgery. The false-negative rate of echocardiography was 14.5%. Echocardiography has significant disadvantages in diagnosing perivalvular abscesses, valve perforations, and left-sided endocarditis, especially for subjects with both aortic and mitral valve infections. The multivariate analysis identified congenital heart disease and small vegetations (< 10 mm) as independent predictors of false-negative echocardiography results. Conversely, fever and heart murmurs on admission served as protective factors. CONCLUSIONS: Under some circumstances, echocardiography provides inconsistent results compared with surgical findings, and negative echocardiography results do not rule out IE. The diagnosis of IE depends on comprehensive evaluations using multiple methods.

Dynamic Changes in Liver Stiffness Measured by Transient Elastography Predict Clinical Outcomes Among Patients With Chronic Hepatitis B.

OBJECTIVES: We aimed to evaluate the validity of transient elastography in monitoring the antiviral outcomes in patients with chronic hepatitis B. METHODS: This study included 108 patients treated with nucleos(t)ide analogues and 67 patients treated with interferon (IFN). Liver biopsies were evaluated by the METAVIR score. Transient elastography was performed initially at baseline, 48 weeks, and 96 weeks. Liver tissue was obtained before and after 96 weeks of treatment. The area under the receiver operating characteristic curve was used to examine the diagnostic value of transient elastography in predicting and monitoring outcomes of antiviral treatment. RESULTS: The liver stiffness value correlated well with the baseline alanine aminotransferase level (r = 0.33; P < .001) and was significantly different among various stages of liver fibrosis (P < .001). In the nucleos(t)ide analogue group, the mean pretreatment and posttreatment liver stiffness values ± SD were 8.7 ± 3.1 and 5.9 ± 1.6 kPa, respectively (P < .001), and they were 9.2 ± 3.7 and 7.2 ± 1.9 kPa (P < .001) in the IFN group. Although the liver stiffness values at baseline between the groups were similar (P = .45), they were 5.9 ± 1.6 kPa in the nucleos(t)ide analogue group and 7.2 ± 1.9 kPa in the IFN group after 48 weeks of treatment (P < .001). With the decreased magnitude liver stiffness for predicting the improvement in liver fibrosis, the area under the receiver operating characteristic curve was 0.68 (P = .029). When the decreased magnitude of liver stiffness was 4.1 kPa or higher, the sensitivity and specificity for predicting a histologic response were 88.2% and 50.0%. CONCLUSIONS: Our findings suggest that transient elastography is an effective measurement tool for diagnosing and monitoring the histologic response in patients with chronic hepatitis B during antiviral treatment and can help avoid multiple liver biopsies.

Potential effects of telbivudine and entecavir on renal function: a systematic review and meta-analysis.

BACKGROUND: To assess the potential effects of telbivudine (LdT) and entecavir (ETV) on renal function in patients with chronic hepatitis B (CHB), we performed a meta-analysis of the relevant data available on these agents to evaluate their effects on the estimated glomerular filtration rate (eGFR) during treatment. METHODS: The PubMed, EMBASE, Scopus, CNKI (China National Knowledge Infrastructure), Cochrane Library, and WanFang databases were searched for relevant articles appearing in the literature up to July 1, 2015. A total of 6 studies (1960 CHB patients) with 1-year eGFR outcomes were retrieved and analyzed. RESULTS: Generally, the results of the 6 studies analyzed showed that eGFR was improved after LdT treatment, but was decreased after ETV treatment. Using a fixed-effects approach, the change in eGFR was found to be significantly different between LdT and ETV treatment (Z = 3.64; P = 0.0003). Whereas the eGFR was slightly decreased with ETV compared with baseline (-1.45 mL/min/1.73 m(2)), the eGFR was improved with LdT (2.99 mL/min/1.73 m(2)) after 1 year of treatment. An overall test of effect in the meta-analysis showed that the eGFR in LdT-treated patients was significantly improved after 1-year of treatment (Z = 3.71; P = 0.0002). CONCLUSION: This meta-analysis has confirmed that LdT has a renal protective effect whereas ETV does not. However, whether the benefit on renal function outweighs the occurrence of resistance in specific clinical situations is not yet clear.

Aspartate aminotransferase to platelet ratio index - a reliable predictor of therapeutic efficacy and improvement of Ishak score in chronic hepatitis B patients treated with nucleoside analogues.

BACKGROUND: No studies have investigated the predictive and monitoring efficacy of aspartate aminotransferase to platelet ratio index in chronic hepatitis B patients undergoing antiviral therapy based on paired Ishak biopsies pre- and post-treatment. We evaluated the efficacy of aspartate aminotransferase to platelet ratio index in monitoring fibrosis improvement in chronic hepatitis B patients treated with nucleoside analogue or interferon. METHODS: Pre- and post-treatment Ishak fibrosis scores of 86 nucleoside-analogue- and 42 interferon-treated patients were retrospectively analyzed. The area under the receiver operating characteristic curve was calculated. RESULTS: In nucleoside-analogue-treated patients, the area under the receiver operating characteristic curve was 0.80 and 0.91 when aspartate aminotransferase to platelet ratio index was used to diagnose fibrosis and cirrhosis, respectively. When the decreased magnitude of aspartate aminotransferase to platelet ratio index was ≥ 0.35, the sensitivity and specificity of predicting fibrosis improvement were 75.8% and 75.0%, respectively. The area under the receiver operating characteristic curve was 0.53 when aspartate aminotransferase to platelet ratio index was used to diagnose fibrosis in 20 interferon-treated patients, while an insufficient patient number in the cirrhosis group prevented the calculation of the area under the receiver operating characteristic curve. The same is true for the remaining 22 interferon-treated patients. CONCLUSIONS: Our study is the first to demonstrate the aspartate aminotransferase to platelet ratio index as a reliable marker in diagnosing and monitoring fibrosis improvement in nucleoside-analogue-treated patients based on paired Ishak biopsies pre- and post-treatment, but the test is not applicable in interferon therapy.

Dynamic comparison between Daan real-time PCR and Cobas TaqMan for quantification of HBV DNA levels in patients with CHB.

BACKGROUND: Hepatitis B virus (HBV) DNA levels are crucial for managing chronic hepatitis B (CHB). It was unclear whether Daan real-time polymerase chain reaction test (Daan test) or COBAS TaqMan HBV DNA Test (Cobas TaqMan) was superior in measuring different HBV DNA levels in clinical specimens. METHODS: We enrolled 67 treatment-naïve, HBV surface antigen-positive CHB patients (high baseline viral levels) who received either lamivudine/adefovir or entecavir. Serum samples were tested at baseline and treatment week 24 using the Daan test and Cobas TaqMan. RESULTS: In the 67-baseline samples, the HBV DNA levels with the Cobas TaqMan (7.90 ± 0.73 log10 IU/mL) were significantly greater than those of the Daan test (7.11 ± 0.44 log10 IU/mL; P < 0.001). Of the 67 24-week samples (low viral levels), the Cobas TaqMan detected 59 (88.1%; 8 undetected); the Daan test detected 33 (49.3%; 34 undetected; P < 0.001). The Cobas TaqMan detected HBV DNA in 26 of 34 samples undetectable by the Daan test (range, 1.4-3.7 log10 IU/mL) or 38% of samples (26/67). The reductions in viral load after 24 weeks of oral antiviral treatment in the 33 samples that were positive for both the Daan test and the Cobas TaqMan test were significantly different (3.59 ± 1.11 log10 IU/mL versus 4.87 ± 1.58 log10 IU/mL, respectively; P = 0.001). Spearman correlation analysis showed positive correlation between results from two tests (rp = 0.602,P<0.001). The HBV genotypes and the anti-viral treatment did not affect the measurements of the HBV DNA by the Daan assay and the Cobas Taqman assay. CONCLUSION: The Cobas Taqman was more sensitive at low viral loads than the Daan test and the change from complete to partial virological response could affect clinical decisions. The Cobas Taqman may be more appropriate for detection of HBV DNA levels.

The Role of Infiltrated T Lymphocyte in Oral Squamous Cell Carcinoma: Insights into Clinicopathological Characteristics and Prognosis.

Background: To compare and analyze the presence of CD4+ and CD8 + lymphocyte infiltrates in Oral squamous cell carcinoma (OSCC) tissue versus adjacent tissue and their clinical significance. Methods: We enrolled a total of 152 patients diagnosed with OSCC, all of whom had confirmed diagnoses through pathological reports. Clinical and demographics data were extracted from medical records. Tissue microarrays were constructed and immunohistochemical staining for CD4 and CD8 was performed. Findings: The average number of infiltrating CD4+ T cells in OSCC tumor tissue was 1026.22±1163.36 cells/mm2, which did not significantly differ from the count in adjacent tissue, which was 1163.36±1013.23 cells/mm2. However, the number of CD8+ T cell infiltration in tumor tissue was significantly higher than in adjacent tissue (655.25±705.70 vs 504.56±659.26 cells/mm2, p = 0.026). We observed that, among patients who consumed alcohol, the CD4+ T cell infiltration in tumor tissue being significantly lower than that in adjacent tissue (P=0.036). Moreover, the CD8+ T cell infiltration in cancer tissue was significantly higher than in adjacent tissue for T1-2 patients (p=0.005). Patients with higher CD8+ T cell in tumor tissue exhibited significantly improved overall survival (p = 0.043). Multivariate analyses revealed that alcohol consumption had a significant impact on the number of CD4+T lymphocytes in tumor tissue (OR = 0.403, P = 0.033) while T stage was the independent factor affecting CD8+ T lymphocyte infiltration in tumor tissue (OR = 0.459, P = 0.031). Interpretation: OSCC patients with a higher number of CD8+ T lymphocyte infiltration in tumor tissue exhibited an improved prognosis.

Estimated Pulse Wave Velocity as a Novel Non-Invasive Biomarker for Metabolic Syndrome Among People Living with HIV.

Purpose: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH. Patients and Methods: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS. Results: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P < 0.001). According to the ROC curve, the optimal cut-off value of ePWV was 7.4 m/s, and its sensitivity and specificity in diagnosing MetS in PLWH were 79.03% and 64.07%, respectively. Although the 7.4 m/s cutoff increased the false positive rate compared to the traditional cutoff, it significantly reduced the rate of missed diagnoses, effectively identifying 79.03% of PLWH with MetS. Conclusion: ePWV is a non-invasive and convenient novel biomarker with predictive capabilities for MetS in PLWH.

Expression and prognostic significance of the PD-1/PD-L1 pathway in AIDS-related non-Hodgkin lymphoma.

OBJECTIVE: Immune tolerance and evasion play a critical role in virus-driven malignancies. However, the phenotype and clinical significance of programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, in aggressive acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) remain poorly understood, particularly in the Epstein-Barr virus (EBV)-positive subset. METHODS: We used in situ hybridization with EBV-encoded RNA (EBER) to assess the EBV status. We performed immunohistochemistry and flow cytometry analysis to evaluate components of the PD-1/PD-L1/L2 pathway in a multi-institutional cohort of 58 patients with AR-NHL and compared EBV-positive and EBV-negative cases. RESULTS: The prevalence of EBV+ in AR-NHL was 56.9% and was associated with a marked increase in the expression of PD-1/PD-L1/PD-L2 in malignant cells. Patients with AR-NHLs who tested positive for both EBER and PD-1 exhibited lower survival rates compared to those negative for these markers (47.4% vs. 93.8%, p = 0.004). Similarly, patients positive for both EBER and PD-L1 also demonstrated poorer survival (56.5% vs. 93.8%, p = 0.043). Importantly, PD-1 tissue-expression demonstrated independent prognostic significance for overall survival in multivariate analysis and was correlated to elevated levels of LDH (r = 0.313, p = 0.031), increased PD-1+ Tregs (p = 0.006), and robust expression of EBER (r = 0.541, p < 0.001) and PD-L1 (r = 0.354, p = 0.014) expression. CONCLUSIONS: These data emphasize the importance of PD-1-mediated immune evasion in the complex landscape of immune oncology in AR-NHL co-infected with EBV, and contribute to the diagnostic classification and possible definition of immunotherapeutic strategies for this unique subgroup.

Prospective observational study of baloxavir marboxil in adults and adolescents with uncomplicated influenza from China.

Introduction: There are limited data on the efficacy of baloxavir marboxil (baloxavir) versus oseltamivir in Chinese patients with influenza A. Methods: This study is an observational real-world investigation encompassing 246 patients (baloxavir, n = 147; oseltamivir, n = 99) confirmed positive for influenza A. The choice between baloxavir and oseltamivir antiviral treatments was determined collaboratively by the clinician and the patient. A thorough comparative analysis was undertaken between the two groups, examining parameters such as the duration of fever and symptoms, viral load dynamics, lymphocyte changes, and enhancements in health-related quality of life (QoL). Results: No significant differences were observed in demographic data between the two groups. The duration of fever was significantly shorter in the baloxavir group (P < 0.001). However, the duration of symptoms was not significant different (P = 0.167). Multivariable Cox analysis showed the independent factors affecting duration of fever were baloxavir treatment (HR = 2.033, P < 0.001), fever on day 1 (HR = 0.741, P = 0.010) and CRP level (HR = 1.009, P = 0.039). Moreover, sex (HR= 0.660, P = 0.019) and monocyte count (HR = 1.355, P = 0.018) were independent factors affecting the duration of symptoms. No significant difference in change of health-related quality of life (P > 0.05), positive rate of viral antigen on day 3 (P = 0.477) between the two groups. Remarkably, a mutation was observed in one case on the third-day after baloxavir treatment compared with first-day, from cysteine to serine at position 384 of the PA subunit. Conclusion: In the clinical setting, baloxavir demonstrated comparable clinical benefits to oseltamivir, establishing its efficacy as an effective antiviral therapy for Chinese patients with influenza.

A model for predicting high BMI of people living with HIV after receiving antiretroviral therapy.

Objective: The objective of this study was to evaluate the characteristics of high body mass index (BMI) and normal weight people living with HIV after antiretroviral therapy (ART) and establish a model. Methods: A total of 290 people living with HIV after 1 year of ART treatment were enrolled and divided into two groups based on whether their BMI index was <24 or ⩾24 at week 48. The demographic, clinical data were collected and analyzed. Multivariable logistic regression analysis was performed. A model was established and use to predict the occurrence of certain diseases. Results: A total of 290 people living with HIV were included in this study; 200 had a normal BMI (BMI < 24) and 90 were high BMI (BMI ⩾ 24) after 1-year ART. Their baseline characteristics were significantly different in relation to age (p = 0.007), sex distribution (p = 0.040), ART regimen (p = 0.040), alanine aminotransferase levels (p < 0.001), and three major serum lipid levels: triglycerides (p < 0.001), cholesterol (p = 0.011), and low-density lipoprotein (p = 0.005). A multivariate logistic regression analysis resulted in the development of a model for the diagnosis of high BMI and hyperlipidemia. The model score is an independent risk factor for hyperlipidemia (odds ratio = 2.674, p = 0.001) and high BMI (p < 0.001). The model score is significantly correlated with the controlled attenuation parameter (CAP) value (r = 0.230, p < 0.001) and can be used to divide the severity of liver steatosis based on CAP value. Conclusions: This study demonstrated a easy-to-use model to detect high BMI, hyperlipidemia, and liver steatosis in people living with HIV without risk factors for BMI changing at baseline after 1 year of ART treatment.

aMAP Score as a Predictor for Long-Term Outcomes in Patients with HBV-Related Acute-on-Chronic Liver Failure.

BACKGROUND AND AIM: The long-term outcomes of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) remain not well known. This study aimed to investigate whether aMAP score can predict re-hospitalization, hepatocellular carcinoma (HCC) occurrence and long-term mortality in patients with HBV-ACLF. METHODS: A total of 82 patients diagnosed with HBV-ACLF and survived over 6 months were enrolled. The median follow-up period was 105 (75.9, 134.1) months. The Cox proportional hazards or logistic regression analysis was used to determine independent risk factors. Cumulative incidence of HCC and survival rate were evaluated using Kaplan-Meier analysis. RESULTS: Multivariate analysis identified that the aMAP risk score was an independent predictor of re-hospitalization (odds ratio [OR] = 1.112, 95% confidence interval [CI]: 1.021-1.211, p = 0.015), hepatocellular carcinoma occurrence (hazards ratio [HR] = 2.277, 95% CI: 1.014-5.114, p = 0.046) and mortality (HR = 1.366, 95% CI: 1.040-1.794, p = 0.025). High-risk aMAP scores were associated with higher risk of HCC occurrence and mortality. CONCLUSION: A higher aMAP score was an independent risk predictor of re-hospitalization, HCC occurrence and mortality, respectively, in HBV-ACLF patients who survived over 6 months, which can be applicable for early risk stratification and clinical decision.

Loneliness as a mediation from social support leading to a decrease of health-related quality of life among PLWHIV.

This study focused on the mental health of people living with HIV(PLWHIV) and explored their relationship between loneliness and perceived social support, health related quality of life (HRQoL) with a method of structural equation model. We collected clinical and psychological data from consecutively enrolled PLWHIV. A total of 201 PLWHIVs were enrolled and measured with self-reporting survey instruments of UCLA Loneliness Scale, Self-Rating Depression Scale, Self-Rating Anxiety Scale, Social Support Ratio Scale and Short Form Health Survey-36. The levels of loneliness, depression, anxiety, perceived social support and HRQoL were assessed. PLWHIV enrolled were divided into two groups of loneliness and non-loneliness based on their UCLA Loneliness Scale scores. Multivariable analysis indicated that being married is a protective factor associated with loneliness (OR = 0.226; P = 0.032). We further found the loneliness group had a higher level of depression (P < 0.001) and anxiety (P < 0.001), but lower level of HRQoL (P < 0.001) than the non-loneliness group. We found there was a positive linear correlation between social support and HRQoL among the enrolled PLWHIVs (r2 = 0.0592; P = 0.0005). A structural equation model (SEM) was established to evaluate whether the loneliness played as a mediation role between social support and HRQoL. The model showed loneliness as a mediation from social support leading to a decrease of HRQoL. Our findings showed a potential psychological pathway from social support to HRQoL, suggesting the need for interventions focusing on social support may improve poor HRQoL lead by loneliness.

Soluble Programmed Cell Death-1 is a Novel Predictor of HBsAg Loss in Chronic Hepatitis B Patients When Long-Term Nucleos(t)ide Analog Treatment is Discontinued.

Purpose: The immunoinhibitory receptor, programmed death 1 (PD-1), plays a critical role in immune suppression during chronic viral infection. The significance of circulating soluble PD-1 (sPD-1) in patients with chronic hepatitis B who have discontinued long-term nucleos(t)ide analog (NA) treatment remains unknown. Patients and Methods: A prospective cohort study was conducted using serial blood samples from chronic hepatitis B patients who discontinued long-term NA treatment. The current analysis included 115 non-cirrhotic patients with HBV DNA negative and HBsAg positive at the moment of NA discontinuation. Levels of sPD-1 were measured in all available samples using sandwich enzyme-linked immunoassay. Results: Sixty-two patients experienced a clinical relapse and 14 occurred HBsAg loss, with 8-year cumulative rates of 56.6% and 23.4%, respectively. Time-dependent receiver operating characteristic curve analysis for sPD-1 derived 156 pg/mL, which is equivalent to the detectable threshold, as an optimal cut-off value for predicting 8-year clinical relapse. Patients with detectable sPD-1 at end of treatment (EOT) had a significant lower incidence of clinical relapse (48% vs 67%, hazard ratio [HR] 0.454, p = 0.006), but a remarkable higher probability of HBsAg loss (33.7% vs 2.4%, HR 9.17, p = 0.038), compared to those who with undetectable sPD-1, respectively. Conclusion: EOT sPD-1 levels predicted clinical relapse and HBsAg loss after treatment discontinuation and may help to guide a finite NA treatment plan for patients with chronic hepatitis B virus infection.

Hypoalbuminemia predicts inferior outcome in patients with AIDS-related lymphoma.

BACKGROUND: The prognostic value of serum albumin in acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) remains covered. METHODS: We retrospectively analyzed de novo ARL patients from 2013 to 2019 across three centers. Factors correlated with progression-free survival (PFS) and overall survival (OS) were evaluated in Kaplan-Meier, univariate and multivariate Cox proportional hazard models. RESULTS: A total of 86 ARL patients were enrolled with a median follow-up of 34 months. In the cohort, the OS and 2-year PFS rates were 37.5% and 35.4%, respectively. In multivariate models, older age (PFS, hazard ratios [HR] = 1.035, p = 0.037; OS, HR = 1.034, p = 0.041) and hypoalbuminemia (OS, HR = 0.910, p = 0.038) predicted inferior survival. ARL patients with hypoalbuminemia showed worse OS and 2-year PFS (p = 0.028 and p = 0.01, respectively), which was associated with poor Eastern Cooperative Oncology Group performance status (ECOG PS) and higher International Prognosis Index (IPI) score. CONCLUSION: In conclusion, serum albumin at diagnosis is an independent prognostic factor for overall survival in AIDS-related lymphoma.

Risk Factors Associated With Quality of Life in Patients With Hepatitis B Virus Related Cirrhosis.

Aim: To evaluate health-related quality of life (HRQoL) of chronic hepatitis B (CHB) and hepatitis B virus (HBV) related cirrhosis patients and analyzed specific differences in all dimensions of HRQoL. Methods: A total of 349 patients met selection criteria were enrolled. The 36-Item Short-Form Health Survey was adopted. Results: Results showed that the physiological HRQoL of the cirrhotic group was significantly lower than that of the non-cirrhotic group (P = 0.003), the psychological HRQoL was also lower (P = 0.006). HRQoL was significantly negatively correlated with liver stiffness (P = 0.001). We further evaluated the risk factors associated with poor HRQoL in HBV-related cirrhosis patients. Results showed that positive HBV DNA viral load (OR = 6.296, P = 0.041) and HCC family history (OR = 36.211, P = 0.001) were independent factors associated with HRQoL in HBV-related cirrhosis. For better risk stratification of patients, multivariable analyses were conducted to explore the independent factors that affected specific physiological and psychological HRQoL. In specific physiological HRQoL, results show that marital status (OR = 9.971, P = 0.034), positive HBV DNA viral load (OR = 6.202, P = 0.042) and antiviral drugs (OR = 0.45, P = 0.031) were independent factors associated with physiological HRQoL in cirrhosis patients. In psychological HRQoL, only HCC family history was independent risk factors associated with psychological HRQoL (OR = 42.684, P = 0.002). Conclusion: We found that the impaired HRQoL dimensions of HBV related cirrhosis patients differ between the various subpopulations. According to our results, risk stratification, medical decision making and personalizing interventions could be made.

Hepatitis B Core-Related Antigen is a Biomarker for off-Treatment Relapse After Long-Term Nucleos(t)ide Analog Therapy in Patients with Chronic Hepatitis B.

OBJECTIVE: It remains unknown how to stratify the risk of clinical relapse of chronic hepatitis B (CHB) patients after stopping nucleos(t)ide analogs (NAs) antiviral therapy. METHODS: The current post hoc analysis included 122 non-cirrhotic patients with chronic hepatitis B virus infection who were positive for hepatitis B envelope antigen (HBeAg) and discontinued long-term NA therapy after achieving HBeAg seroconversion for a median of 2.5 years. Post hoc analysis of end-of-treatment (EOT) hepatitis B core-related antigen (HBcrAg) levels was performed using a chemiluminescent enzyme immunoassay. RESULTS: A total of 78/122 (63.9%) patients experienced sustained response after NAs cessation, and 44/122 (36.1%) patients experienced clinical relapse. In multivariate analysis, EOT HBcrAg (hazard ratio [HR] = 2.105 95% CI: 1.440-3.077, p < 0.001), hepatitis B surface antigen (HBsAg) ≥100 IU/mL (HR = 4.406, 95% CI 1.567-12.389, p = 0.005) and age (HR = 1.051, 95% CI: 1.010-1.093, p = 0.049) were independently associated with clinical relapse. A cut-off value of 4.0 log10 U/mL of HBcrAg was defined by maximized Youden's index. An EOT HBcrAg level of ≥4.0 log10 U/mL was associated with higher risks of clinical relapse (65.8% vs 23.2%, p<0.001) and HBeAg reversion (27.5% vs 1.6%, p < 0.001). In majority of patients (n = 91) who had a high EOT HBsAg level (≥100 IU/mL), serum HBcrAg level could further discriminate patients at low risk of clinical relapse. Patients with an HBcrAg level ≥4.0 log10 U/mL had significantly higher cumulative incidence rates of clinical relapse (78.1% vs 29.4%, p < 0.001) and HBeAg reversion (29.4% vs 0%, p < 0.001). CONCLUSION: Serum EOT HBcrAg level can be a predictor of off-treatment relapse in patients with CHB. An HBcrAg level of 4.0 log10 U/mL may identify patients at high risk of clinical relapse after treatment cessation.

Association Between Nutritional Risk Screening Score and Prognosis of Patients with Sepsis.

BACKGROUND: Malnutrition is one of the most critical factors affecting patients' risk of infection and length of stay, and it may affect the prognosis of patients with sepsis. There have been no studies that have applied nutritional risk screening tools to stratify patients with sepsis according to prognosis. METHODS: We retrospectively analyzed the clinical data of 425 adult sepsis inpatients who were grouped based on nutritional risk screening (NRS) score, including a nutrition score, disease severity score, and age score. Prognostic factors were analyzed using univariate and multivariate regression analyses. RESULTS: Of the enrolled patients, 174 had an NRS score of ≥3; these patients were older and had a longer hospitalization time but lower body mass index (BMI), albumin (ALB) than others. Univariate Cox regression analysis showed that age, ALB, C-reactive protein (CRP), and NRS score were significantly (P<0.05) associated with in-hospital mortality. Multivariate analysis showed that age (hazard ratio [HR]=1.020, 95% confidence interval [CI]: 1.005-1.036; P=0.008) and ALB (HR=0.924, 95% CI: 0.885-0.966; P<0.001) were independent risk factors for sepsis-related mortality. The Kaplan-Meier analysis revealed that the cumulative in-hospital mortality of sepsis patients with an NRS score of ≥3 was significantly higher than that of patients with an NRS score of <3 (P=0.022). CONCLUSION: NRS scores can effectively risk stratify sepsis patients. Patients with high NRS scores should be monitored more closely to halt further disease progression.