Band 12, Heft 3

Gouty arthritis, often referred to simply as gout, is a disorder of purine metabolism characterized by the deposition of monosodium urate monohydrate (MSU) crystals in multiple systems and organs, especially in joints and their surrounding soft tissue. Gout is a treatable chronic disease, and the main strategy for effective management is to reverse the deposition of MSU crystals by uric acid reduction, and to prevent gout attacks, tophi deposition and complications, and thereby improve the quality of life. However, the frequent association of gout with other conditions such as hypertension, obesity, cardiovascular disease, diabetes, dyslipidemia, chronic kidney disease (CKD) and kidney stones can complicate the treatment of gout and lead to premature death. Here, we review the use of medical imaging techniques for studying gouty arthritis with special interest in the potential role of single photon emission computed tomography (SPECT)/computed tomography (CT) in the clinical management of gout and complications ( e.g ., chronic kidney disease and cardiovascular disease).

Background and Objectives Immunotherapy has become the standard treatment for hepatocellular carcinoma (HCC), but it carries a risk of immune-related adverse events (irAEs) that can be life-threatening. This study employs bibliometric analysis to understand global scientific research on irAEs in cancer, focusing on characteristics and areas of interest. Additionally, a meta-analysis provides a comprehensive overview of irAEs in HCC patients receiving immune checkpoint inhibitor (ICI)-based therapies. Methods We conducted a thorough search of Web of Science Core Collection (WoSCC) publications from 1999 to 2022. R and VOSviewer software were used for analysis. A meta-analysis was performed using data from PubMed, Embase, and the Cochrane Library databases up to March 22, 2022. Trials with HCC patients reporting irAE incidence were included. Quality assessment followed Cochrane risk of bias, Newcastle-Ottawa Scale (NOS), and Methodological Index for Non-Randomized Studies (MINORS). We used random-effects or fixed-effects models based on I2 values. Primary outcomes included any-grade irAEs and grade ≥ 3 irAEs. This review and meta-analysis are registered in PROSPERO as CRD42022318885. Results In bibliometric analysis, we included 2946 papers, showing a consistent rise in annual publications on irAEs in cancer research. Frequent keywords were “nivolumab”, “immune checkpoint inhibitor”, and “immune-related adverse event”. “Hepatocellular carcinoma” emerged as a prominent research focus linked to irAEs. We conducted a comprehensive meta-analysis on irAE incidence in HCC patients, including 29 studies. The overall incidence of any-grade irAEs was 61.0% (95% CI 38.5%–81.3%), and grade ≥ 3 irAEs was 13.2% (95% CI 7.9%–19.6%). Treatment-related mortality occurred in 3.1% (95% CI 0.8%–6.3%), with treatment discontinuation at 10.7% (95% CI 6.3%–16.0%). Reactive cutaneous capillary endothelial proliferation (RCCEP) was the most common any-grade irAE, while elevated aspartate aminotransferase (AST) was the most common grade ≥ 3 irAE. Treatment strategies were independently associated with specific irAEs, as indicated by multivariable analysis. Conclusion This study provides valuable insights into the current research landscape of irAEs in cancer and ofers a comprehensive overview of irAEs in HCC patients undergoing ICI-based therapy. The relatively high incidence of irAEs and their association with treatment strategies emphasize the need for careful management by clinicians when treating HCC patients. These findings offer significant guidance for optimizing care and treatment for HCC patients.

Background and objectives Cumulative evidence confirms that mild renal dysfunction (MRD) is correlated with many cardiovascular risk factors and increases cardiovascular morbidity and mortality. The purpose of this study was to establish an effective nomogram for predicting the risk of MRD in the rural population of Northeast China. Methods We analyzed the reports of 4944 subjects from the Northeast China Rural Cardiovascular Health Study (NCRCHS). All the participants completed the questionnaires, anthropometric measurements, and blood tests during the baseline study (2012–2013) and the follow-up study during 2015–2017 (an average of 4.6 years). The Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used to calculate the estimated glomerular filtration rate (eGFR), and eGFR in the range of 60–90 mL/min/1.73m2 was defined as MRD. Results The study revealed that a total of 889 subjects (18.0%) had MRD. Multivariate logistic analysis showed that annual income, abdominal obesity, hypertension, hyperglycemia, and frequent tea consumption were the independent risk factors ( P < 0.05) for MRD. Thereafter, a nomogram with an area under the receiver operating characteristic curve (AUC) of 0.705 was constructed to accurately predict MRD. The calibration plot also showed an excellent consistency between the probability of prediction and observation. Conclusion We constructed a nomogram based on epidemiological data, which could provide an individual prediction of MRD with good accuracy.

Objective To compare the effects of metaraminol and norepinephrine on hemodynamics and kidney injury in the treatment of septic shock, and calculate the conversion dose ratio between the two vasopressors. Methods This randomized controlled study was performed on 15 Guizhou miniature pigs. Septic shock was induced by fecal peritonitis in 10 animals, and 5 were used as a sham-operated group (shams). Fluid resuscitation and vasopressors were initiated 30 min after the onset of septic shock. The septic shock pigs were randomly assigned to receive one of the two drugs to restore and maintain mean arterial pressure (MAP) ≥ 65 mmHg for 3 h. Hemodynamics and heart rate were continuously monitored. Results There was no significant difference in MAP, heart rate, cardiac output (CO) and central venous pressure (CVP) between the two groups after treatment. No arrhythmias such as atrial fibrillation and ventricular fibrillation presented during continuous monitoring. After septic shock, the animals showed obvious kidney injury. In addition, compared with norepinephrine, the creatinine at 3 h was significantly lower with metaraminol. According to propensity score matching, the ratio of 6: 1 was considered appropriate for the dose equivalence calculation of metaraminol (μg·kg-1·min-1): norepinephrine (μg·kg-1·min-1). Conclusion Metaraminol has a similar pressor effect to norepinephrine in septic shock; it does not increase heart rate and aggravate kidney injury after shock compared with norepinephrine. And our research may provide some laboratory evidence for the clinical usage of metaraminol.

Background and objectives Comprehensive data analyses in heart failure research can provide academics with information and help policymakers formulate relevant policies. We collected data from reports published between 1945 and 2021 to identify research topics, trends, and cross-domains in the heart failure disease literature. Methods Text fragments were extracted and clustered from the titles and abstracts in 270617 publications using artificial intelligence techniques. Two algorithms were used to corroborate the results and ensure that they were reliable. Experts named themes and document clusters based on the results of these semiautomated methods. Using consistent methods, we identified and flagged 107 heart failure topics and 16 large document clusters (divided into two groups by time). The annual vocabularies of research hotspots were calculated to draw attention to niche research fields. Results Clinical research is an expanding field, followed by basic research and population research. The most frequently raised issues were intensive care treatment for heart failure, applications of artificial intelligence technologies, cardiac assist devices, stem cells, genetics, and regional distribution and use of heart failure-related health care. Risk scoring and classification, care for patients, readmission, health economics of treatment and care, and cell regeneration and signaling pathways were among the fastest-growing themes. Drugs, signaling pathways, and biomarkers were all crucial issues for clinical and basic research in the entire population. Studies on intelligent medicine and telemedicine, interventional therapy for valvular disease, and novel coronavirus have emerged recently. Conclusion Clinical and population research is increasingly focusing on the customization of intelligent treatments, improving the quality of patients’ life, and developing novel treatments. Basic research is increasingly focusing on regenerative medicine, translational medicine, and signaling pathways. Additionally, each research field exhibits mutual fusion characteristics. Medical demands, new technologies, and social support are all potential drivers for these changes.

Background and objectives Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. An epigenetic-based synthetic lethal strategy provides a novel opportunity for PDAC treatment. Finding more DNA damage repair (DDR)-related or cell fate-related molecules with aberrant epigenetic changes is becoming very important. Family with sequence similarity 110C ( FAM110C ) is a cell fate-related gene and its function in cancer remains unclear. Methods Seven cell lines, 34 cases of intraductal papillary mucinous neoplasm (IPMN), 15 cases of mucinous cystic neoplasm (MCN) and 284 cases of PDAC samples were employed. Methylation-specific PCR, western blot, CRISPR knockout, immunoprecipitation and a xenograft mouse model were used in this study. Results FAM110C is methylated in 41.18% (14/34) of IPMN, 46.67% (7/15) of MCN and 72.89% (207/284) of PDAC, with a progression trend from IPMN/MCN to pancreatic cancer ( P = 0.0001, P = 0.0389). FAM110C methylation is significantly associated with poor overall survival (OS) ( P = 0.0065) and is an independent prognostic marker for poor OS ( P = 0.0159). FAM110C inhibits PDAC cells growth both in vitro and in vivo , serving as a novel tumor suppressor. FAM110C activates ATM and NHEJ signaling pathways by interacting with HMGB1. Loss of FAM110C expression sensitizes PDAC cells to VE-822 (an ATR inhibitor) and MK-8776 (a CHK1 inhibitor). Conclusion FAM110C methylation is a potential diagnostic and prognostic marker in PDAC, and its epigenetic silencing sensitizes PDAC cells to ATR/CHK1 inhibitors.

Background and Objectives Overcoming ATP-binding cassette subfamily G member 2 (ABCG2)-mediated multidrug resistance (MDR) has attracted the attention of scientists because one of the critical factors resulting in MDR in cancer is the overexpression of ABCG2. RN486, a Bruton’s Tyrosine Kinase (BTK) inhibitor, was discovered to potentially reverse ABCB1-mediated MDR. However, there is still uncertainty about whether RN486 has a reversal off-target impact on ABCG2-mediated MDR. Methods MTT assay was used to detect the reversal effect of RN486 on ABCG2-overexpressing cancer cells. The ABCG2 expression level and subcellular localization were examined by Western blotting and immunofluorescence. Drug accumulation and eflux assay and ATPase assay were performed to analyze the ABCG2 transporter function and ATPase activity. Molecular modeling predicted the binding between RN486 and ABCG2 protein. Results Non-toxic concentrations of RN486 remarkably increased the sensitivity of ABCG2-overexpressing cancer cells to conventional anticancer drugs mitoxantrone and topotecan. The reversal mechanistic studies showed that RN486 elevated the drug accumulation because of reducing the eflux of ABCG2 substrate drug in ABCG2-overexpressing cancer cells. In addition, the inhibitory efect of RN486 on ABCG2-associated ATPase activity was also verified. Molecular docking study implied a strong binding afinity between RN486 and ABCG2 transporter. Meanwhile, the ABCG2 subcellular localization was not altered by the treatment of RN486, but the expression level of ABCG2 was down-regulated. Conclusions Our studies propose that RN486 can antagonize ABCG2-mediated MDR in cancer cells via down-regulating the expression level of ABCG2 protein, reducing ATPase activity of ABCG2 transporter, and inhibiting the transporting function. RN486 could be potentially used in conjunction with chemotherapy to alleviate MDR mediated by ABCG2 in cancer.

Background and Objectives Fever of unknown origin (FUO) has long been a cause for concern among clinicians, and its spectrum has evolved with progress in medicine. This study aimed to investigate the distribution of causes of FUO in China between 2013 and 2022 to facilitate the clinical understanding of the etiology of FUO. Materials and Methods Case series of FUO in China published between 2013 and 2022 were retrieved from PubMed, Wanfang Data, and CNKI databases and retrospectively analyzed. The rates of different causes of FUO were calculated, and these data were compared with previously published distributions of causes of FUO in China. Results The causes of FUO with the highest rates from the 51 identified case series ( n = 19,874) were infectious, autoimmune, and neoplastic diseases (59.6%, 14.3%, and 7.9%, respectively). A comparison of a subset (43 case series subdivided by disease category, n = 16,278) with previously reported data revealed an increased rate of FUO attributed to infectious diseases in the past decade, with a significantly higher rate attributed to bloodstream infections (10.0% vs . 4.8%) and a significantly lower rate attributed to tuberculosis (9.3% vs . 28.4%), compared with the rates from the previous period. In contrast, the rates of FUO attributed to both autoimmune and neoplastic diseases decreased, with significantly decreased rates attributed to adult-onset Still's disease among autoimmune diseases (4.6% vs . 8.5%) and lung cancer among neoplastic diseases (0.6% vs . 1.6%). Conclusion Despite an overall increase in the rate attributed to infectious diseases, that attributed to tuberculosis has decreased. The rates attributed to both autoimmune and neoplastic diseases have also decreased.

Background Morphologic changes in the gallbladder and gallstones are common in cirrhotic patients, but their associations with outcomes of cirrhotic patients are unclear. Methods We retrospectively enrolled 206 cirrhotic patients and measured their gallbladder length and width, gallbladder wall thickness, presence of gallstones, and gallstones’ length and width in axial contrast-enhanced computed tomography (CT) images. X-tile software was utilized to calculate the optimal cutoff values of these parameters for evaluating survival and hepatic decompensation events in the cirrhosis group. Their associations with survival were explored by Cox regression analyses and Kaplan–Meier curve analyses. Their associations with hepatic decompensation events were evaluated by competing risk analyses and Nelson-Aalen cumulative risk curve analyses where death was a competing event. Results Cirrhotic patients with gallbladder length < 72 mm had a significantly higher cumulative survival rate than those with a length of ≥ 72 mm ( P = 0.049 by log-rank test), but gallbladder width, gallbladder wall thickness, presence of gallstones, and gallstones’ length and width were not significantly associated with survival ( P = 0.10, P = 0.14, P = 0.97, P = 0.73, and P = 0.73 by log-rank tests, respectively). Cirrhotic patients with gallbladder wall thickness < 3.4 mm had a significantly lower cumulative rate of hepatic decompensation events than those with a wall thickness of ≥ 3.4 mm ( P = 0.02 by Gray’s test), but gallbladder length and width, presence of gallstones, and gallstones’ length and width were not significantly associated with hepatic decompensation events ( P = 0.15, P = 0.15, P = 0.54, P = 0.76, and P = 0.54 by Gray’s tests, respectively). Conclusion Changes in gallbladder length and gallbladder wall thickness, rather than gallstone parameters, may be in parallel with the long-term outcomes of cirrhotic patients.