Impact of Thyroid Function on the Prevalence and Mortality of Metabolic Dysfunction-Associated Fatty Liver Disease.

CONTEXT: Thyroid function variation within the thyroxine reference range has negative metabolic effects. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed definition. OBJECTIVE: We aim to explore the effects of thyroid function status on prevalence and mortality of MAFLD. METHODS: Data of 10 666 participants from the Third National Health and Nutrition Examination Survey (NHANES III) were used. MAFLD was diagnosed based on the new definition. Thyroid function variation within the thyroxine reference range was defined based on thyroid-stimulating hormone (TSH) levels: subclinical hyperthyroidism, <0.39 mIU/L; strict-normal thyroid function, 0.39-2.5 mIU/L; and low thyroid function, >2.5 mIU/L, which comprised low-normal thyroid function (2.5-4.5 mIU/L) and subclinical hypothyroidism (> 4.5 mIU/L). Logistic and Cox regression were used in multivariate analysis. RESULTS: Low thyroid function is independently associated with MAFLD (odds ratio: 1.27). Compared with strict-normal thyroid function, subclinical hypothyroidism was significantly associated with increased risk for all-cause and cardiovascular mortality in the total population (hazard ratio [HR] for all-cause: 1.23; cardiovascular: 1.65) and MAFLD population (HR for all-cause: 1.32; cardiovascular: 1.99); meanwhile, in the low-normal thyroid function group, an increasing trend in mortality risk was observed. Furthermore, low thyroid function also showed significant negative impact on mortality in the total and MAFLD population. Among thyroid function spectrum, mild subclinical hypothyroidism showed the highest HRs on mortality. CONCLUSIONS: Low thyroid function is independent risk factor of MAFLD and is associated with increased risk for all-cause and cardiovascular mortality in the MAFLD population. Reevaluation of TSH reference range should be considered.

Antiviral prophylaxis or preemptive therapy for cytomegalovirus after liver transplantation?: A systematic review and meta-analysis.

Background: To conduct a meta-analysis with the aim of comparing the outcomes of antiviral prophylaxis and preemptive therapy for the prevention of cytomegalovirus (CMV) infection in liver transplant (LT) recipients. Methods: We searched databases for qualified studies up until March 2022. Finally, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity. Results: With a total of 1834 LT patients, the pooled incidence of CMV infection and CMV disease in the overall LT recipients using antiviral prophylaxis and preemptive therapy were 24.7% vs. 40.4% and 6.4% vs. 9.4%, respectively. Our meta-analysis exhibited a significant reduction in the incidence of CMV infection due to antiviral prophylaxis when compared to preemptive therapy in the high-risk group (OR: 6.67, 95% CI: 1.73, 25.66; p = 0.006). In contrast, there was a significant reduction in the incidence of late-onset of CMV disease in preemptive therapy compared to antiviral prophylaxis in the high-risk group (OR: 0.29, 95% CI: 0.12, 0.74; p = 0.009). However, the incidence of CMV disease, allograft rejection, graft loss, drug related adverse effects, opportunistic infections and mortality did not differ significantly between both the interventions (all p> 0.05). Conclusions: We found the use of antiviral prophylaxis, compared with preemptive therapy, is superior in controlling CMV infection and prolonging the time to CMV disease in LT recipients without an increased risk of opportunistic infections, allograft rejection, graft loss, drug related adverse effects, development of drug resistance, and mortality.

Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?-A Systematic Review and Meta-Analysis.

Background: The probable impact of a maintenance immunosuppressant (IS) on liver transplant (LT) recipients with coronavirus disease 2019 (COVID-19) remains unexplored. Our specific aim was to approximate the prognosis of LT recipients with COVID-19 on the standard maintenance IS. Method: We searched separate databases for the qualified studies in between December 2019 and June 25, 2021. Ultimately, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity. Results: In a total of eight studies and 509 LT recipients with COVID-19, the pooled rates of severity and mortality during all the combined immunosuppressive therapies were 22.4 and 19.5%, respectively. Our study sufficiently showed that an immunosuppressive therapy in LT recipients with COVID-19 was significantly associated with a non-severe COVID-19 [odds ratio (OR): 11.49, 95% CI: 4.17-31.65; p < 0.001] and the survival of the patients (OR: 17.64, 95% CI: 12.85-24.22; p < 0.001). Moreover, mammalian target of rapamycin inhibitor (mTORi) typically had the lowest rate of severity and mortality compared to other ISs such as calcineurin inhibitors (CNIs), steroids, and antimetabolites, i.e., severity (13.5 vs. 21.1, 24.7, and 26.3%) and mortality (8.3 vs. 15, 17.2, and 12.1%), respectively. Contrary to the general opinions, our meta-analysis showed comorbidities such as diabetes, hypertension, cardiopulmonary disorders, chronic kidney disease (CKD), age >60, the duration of LT to the diagnosis of COVID-19, primary disease for LT, and obesity were not significantly associated with the severity and mortality in LT recipients with COVID-19 under an immunosuppressive therapy. However, our pooled analysis found that LT recipients with COVID-19 and without comorbidities have a less severe disease and low mortality rate compared to those with both COVID-19 and comorbidities. Conclusions: In conclusion, LT recipients with COVID-19 undergoing immunosuppressive therapies are not significantly associated with the severity and mortality. Therefore, taking the risk of organ rejection into a key consideration, a complete withdrawal of the IS may not be wise. However, mycophenolate mofetil (MMF) might be discontinued or replaced from an immunosuppressive regimen with the CNIs- or mTORis-based immunosuppressive therapy in some selected LT recipients with COVID-19, depending upon the severity of the disease.

The synergistic fungicidal effect of low-frequency and low-intensity ultrasound with amphotericin B-loaded nanoparticles on C. albicans in vitro.

It is difficult to effectively eradicate C. albicans using traditional antifungal agents, mainly because the low permeability of the C. albicans cell wall creates strong drug resistance. The aim of this study was to investigate the synergistic fungicidal effect and the underlying mechanisms of low-frequency and low-intensity ultrasound combined with a treatment of amphotericin B-loaded nanoparticles (AmB-NPs) against C. albicans. AmB-NPs were prepared by a poly(lactic-co-glycolic acid) (PLGA) double emulsion method. C. albicans was treated by AmB-NPs combined with 42 kHz ultrasound irradiation at an intensity of 0.30 W/cm2 for 15 min. The results demonstrate that the application of ultrasound enhanced the antibacterial effectiveness of AmB-NPs (P < 0.01), and the antifungal efficiency increased significantly with increasing AmB concentration of drug-loaded nanoparticles under ultrasonic irradiation. Additionally, the mycelial morphology of C. albicans suffered from the most severe damage and loss of normal microbial morphology after the combined treatment of AmB-NPs and ultrasound, as revealed by electron microscope. Furthermore, we verified the safe use of low-frequency ultrasound on exposed skin and discussed the potential mechanism of ultrasound enhanced fungicidal activity. The results reveal that the mechanism may be associated with the ultrasound cavitation effect and an increase in intracellular reactive oxygen species.

The prevalence and clinicopathological features of breast cancer patients with hepatitis B virus infection in China.

We performed a case-control study to investigate the prevalence and clinicopathological features of breast cancer patients with hepatitis B virus (HBV) infection in China. The clinical data for 2,796 female patients with newly diagnosed, primary breast cancer were evaluated. A total of 234 breast cancer patients with HBV infection (the case group; positive for hepatitis B surface antigen [HBsAg]) and 444 breast cancer patients without HBV infection (the control group; negative for HBsAg, hepatitis B surface antibody, hepatitis B envelope antigen, hepatitis B envelope antibody, and hepatitis B core antibody) were selected for study. Analysis of the clinicopathological features revealed that the metastatic axillary lymph node ratio was lower in the case group than the control group, as was the proportion of patients with pathological T stage ≥T2. No differences in the expression levels of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, p53, or Ki67 were observed between the case and control groups. These data indicate that the rate of HBV infection is high among female breast cancer patients in China, and that HBsAg-positive breast cancer patients were generally diagnosed at an earlier stage and had fewer lymph node metastases.

Clinical study on the relationship between hepatitis B virus infection and risk of breast cancer: a large sized case-control and single center study in southwest of China.

PURPOSE: Chronic hepatitis C virus (HCV) infection is reported to be associated with early-onset breast cancer, while, as a hepadnavirus, hepatitis B virus(HBV) infection is more common than HCV in China. In this article, it is aimed to study the relationship between HBV infection and risk of breast cancer in China. METHODS: The clinical data of 2452 cases of initially diagnosed breast cancer and 1926 cases of benign breast disease (as controls) with the consecutive reports of HBV serological markers and liver function tests, available in the Electronic Medical Records of the Breast Cancer Center of Chongqing, the southwest of China, from January 2011 to March 2015, were collected for analysis. RESULTS: The average age of the initially diagnosed breast cancer patients was 50.3±11.3 years with the age peaking about 40- 49yeaers (39.7%). The positive rate (8.2%) of hepatitis B surface antigen in breast cancer patients was relatively higher than that (7.8%) in controls (P>0.05). While, the positive rate (66.4%)of hepatitis B core antibody in breast cancer patients was significantly higher than that (53.7%) in controls (P<0.05), so were the similar results in the age groups of 40-49 years, after multiple layer analysis stratified by age and compare HBV markers adjusting age with binary logistic regression. Meanwhile, the status of albumin, aminotransferase and aspartate transaminase (41.4 g/L, 22.9 U/L, 22.0 U/L) in breast cancer patients were significantly poorer than those (44.1 g/L,16.8 U/L, 19.2 U/L) in controls (P<0.05). CONCLUSIONS: Exposure to HBV infection may be a risk factor for breast cancer and may be also related to the earlier age onset of breast cancer (peaked around 40-49 years) among Chinese females.

Effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki-67 in Chinese breast cancer patients: A retrospective study of 525 patients.

This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and ki67 in Chinese female breast cancer patients. The expression of estrogen receptor (ER), progesterone receptor (PR) and Ki67 among 525 neoadjuvant chemotherapy cases was studied by immunohistochemistry (IHC). Differences between specimens made through preoperative core needle biopsy (CB) and excised tissue biopsy (EB) were observed. The positive rates of ER, PR and Ki67 in CB and EB were 65.3 and 63.2%, 51.0% and 42.6%, 65.6% and 43.4% respectively. The expression of ER, PR and Ki67 in CB and EB had no statistically significant difference. However, after neoadjuvant chemotherapy, the discordance rates of ER, PR and Ki67 were 15.2% (79/521), 26.9% (140/520), and 44.8% (225/502), respectively. The ER, PR, and Ki67 status changed from positive to negative in 7.5% (39/521), 13.3% (69/520), and 21.1% (106/502) of the patients, whereas ER, PR and Ki67 status changed from negative to positive in 7.7% (40/521), 13.6% (71/520), and 23.7% (119/502) of the patients, respectively. These results showed that the status of some biomarkers changes after neoadjuvant chemotherapy and biomarker status needs to be reexamined to optimize adjuvant systemic therapy and better prognosis assessment.

Does hepatitis B virus infection cause breast cancer?

Lifestyle and family history are two of the most important risk factors for breast cancer (BC). However, these risk factors cannot explain the differences in the incidence and early BC onset among Chinese females compared to their western counterparts. We propose in this hypothesis the potential mechanism of indirect oncogenesis of hepatitis B virus (HBV) in causing BC through its persistence as occult infection and continuous replication with long term subtle liver damage. Estrogen is mainly deactivated in the liver and long term necro-inflammatory damage to liver may result in persistent high level of estrogen, which is a dominant risk factor for BC. HBV may also directly affect the breast cells through its cis and trans effects of HBx which may act as oncoprotein. Given the recognised aetiologic association between oestrogen and breast cancer risk, there is biological plausibility that dietary soy and vegetable intake which is rich in the Chinese diet may have anti-carcinogenic effect on the breast. The seemingly conflicting phenomenon of early age onset and lower BC incidence in China might be due to wide imbalance in the amount of exposure to carcinogenic factor (e.g., HBV infection) for decades and the carcinoprotective exposure levels (e.g., isoflavonoids and flavonoids intake). For example, the increase in carcinoprotective levels would lead to lower incidence of breast cancer and vice versa. Although the focus of this personal view is on HBV, this by no means negates the roles of other known risk factors in breast-cancer development. Characterisation of the role of HBV in BC could potentially benefit Chinese females by decreasing incidence and increasing overall survival.

Chemosensitization role of fulvestrant in combination with chemotherapy in postmenopausal hormone receptor positive and human epidermal growth factor negative metastatic breast cancer.

In metastatic breast cancer (MBC), hormone receptor positive (HR+), human epidermal growth factor negative (HER2-) subtype accounts for the majority. With various new modalities available to prolong life span in this group of patients, the effect is distant from optimum. Prevalent strategy of treating postmenopausal HR+ HER2- MBC is application of chemotherapy (CT) after progression of disease on endocrine therapy (ET) of several lines. Generally, ET targets HR+ ingredients and CT works better with HR- tumor cells. HR+ MBC, though hormone-sensitive, has HR- portion which reacts poorly to ET. Thus, sequential use of ET and CT neglects its insensitive part and gives rise to drug resistance, while alleviation of tumor burden is the top priority in metastatic setting. Chemohormonal therapy (i.e. concomitant use of ET and chemotherapy) complements for the shortcoming of current therapy strategy targeting both HR+ and HR- ingredients theoretically. Fulvestrant, a pure estrogen receptor antagonist and down-regulator, could be a promising agent using concurrently with CT based on chemosensitizing character shown in preclinical and pilot clinical studies. It is hypothesized in this article that chemohormonal therapy with concurrent fulvestrant and CT would be a promising strategy in postmenopausal HR+ HER2- MBC patients. Proof of this hypothesis would help control evolvement of tumor burden and acquirement of drug resistance over a short period of time.

Diagnosis prevention and treatment for PICC-related upper extremity deep vein thrombosis in breast cancer patients.

AIM: To study the incidence, diagnosis, prevention and treatment of peripherally inserted central catheter (PICC)-related upper extremity deep vein thrombosis (DVT) in breast cancer patients using a PICC catheter for chemotherapy. METHODS: The data of the incidence, diagnosis and treatment of PICC-related upper extremity DVT in 187 breast cancer patients using a PICC catheter for chemotherapy, from August 2009 to July 2011 were retrospectively analyzed. RESULTS: In total 188 PICC were inserted between August 2009 and July 2011 and followed up for a total of 14 399 catheter-days (median placement, 76.6 days; range, 1 to 170 days). Four (2.1%) of 188 PICC were removed as a result of PICC-related upper extremity DVT in 14 to 112 catheter-days, at a rate of 0.28/1000 catheter-days. CONCLUSION: The use of PICCs in breast cancer patients for chemotherapy is safe and effective. However, some patients may develop catheter-related upper extremity DVT. In order to minimize complications, we should pay attention to its early symptoms and signs, as well as the timely removal of the catheter and appropriate anti-coagulant treatment.