Prognostic Value of Cardiac MRI and FDG PET in Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis.

Background There is no consensus regarding the relative prognostic value of cardiac MRI and fluorodeoxyglucose (FDG) PET in cardiac sarcoidosis. Purpose To perform a systematic review and meta-analysis of the prognostic value of cardiac MRI and FDG PET for major adverse cardiac events (MACE) in cardiac sarcoidosis. Materials and Methods In this systematic review, MEDLINE, Ovid Epub, CENTRAL, Embase, Emcare, and Scopus were searched from inception until January 2022. Studies that evaluated the prognostic value of cardiac MRI or FDG PET in adults with cardiac sarcoidosis were included. The primary outcome of MACE was assessed as a composite including death, ventricular arrhythmia, and heart failure hospitalization. Summary metrics were obtained using random-effects meta-analysis. Meta-regression was used to assess covariates. Risk of bias was assessed using the Quality in Prognostic Studies, or QUIPS, tool. Results Thirty-seven studies were included (3489 patients with mean follow-up of 3.1 years ± 1.5 [SD]); 29 studies evaluated MRI (2931 patients) and 17 evaluated FDG PET (1243 patients). Five studies directly compared MRI and PET in the same patients (276 patients). Left ventricular late gadolinium enhancement (LGE) at MRI and FDG uptake at PET were both predictive of MACE (odds ratio [OR], 8.0 [95% CI: 4.3, 15.0] [P < .001] and 2.1 [95% CI: 1.4, 3.2] [P < .001], respectively). At meta-regression, results varied by modality (P = .006). LGE (OR, 10.4 [95% CI: 3.5, 30.5]; P < .001) was also predictive of MACE when restricted to studies with direct comparison, whereas FDG uptake (OR, 1.9 [95% CI: 0.82, 4.4]; P = .13) was not. Right ventricular LGE and FDG uptake were also associated with MACE (OR, 13.1 [95% CI: 5.2, 33] [P < .001] and 4.1 [95% CI: 1.9, 8.9] [P < .001], respectively). Thirty-two studies were at risk for bias. Conclusion Left and right ventricular late gadolinium enhancement at cardiac MRI and fluorodeoxyglucose uptake at PET were predictive of major adverse cardiac events in cardiac sarcoidosis. Limitations include few studies with direct comparison and risk of bias. Systematic review registration no. CRD42021214776 (PROSPERO) © RSNA, 2023 Supplemental material is available for this article.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Noncontrast MRI for Hepatocellular Carcinoma Detection: A Systematic Review and Meta-analysis - A Potential Surveillance Tool?

BACKGROUND AND AIMS: This meta-analysis investigates the diagnostic performance of non-contrast magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma (HCC). METHODS: A systematic review was performed to May 2020 for studies which examined the diagnostic performance of non-contrast MRI (multi-sequence or diffusion-weighted imaging (DWI)- alone) for HCC detection in high risk patients. The primary outcome was accuracy for the detection of HCC. Random effects models were used to pool outcomes for sensitivity, specificity, positive likelihood ratio (LR) and negative LR. Subgroup analyses for cirrhosis and size of the lesion were performed. RESULTS: Twenty-two studies were included involving 1685 patients for per-patient analysis and 2128 lesions for per-lesion analysis. Multi-sequence non-contrast MRI (NC-MRI) using T2+DWI±T1 sequences had a pooled per-patient sensitivity of 86.8% (95%CI:83.9-89.4%), specificity of 90.3% (95%CI:87.3-92.7%), and negative LR of 0.17 (95%CI:0.14-0.20). DWI-only MRI (DW-MRI) had a pooled sensitivity of 79.2% (95%CI:71.8-85.4%), specificity of 96.5% (95%CI:94.3-98.1%) and negative LR of 0.24 (95%CI:1.62-0.34). In patients with cirrhosis, NC-MRI had a pooled per-patient sensitivity of 87.3% (95%CI:82.7-91.0%) and specificity of 81.6% (95%CI:75.3-86.8%), whilst DWI-MRI had a pooled sensitivity of 71.4% (95%CI:60.5-80.8%) and specificity of 97.1% (95%CI:91.9-99.4%). For lesions <2 cm, the pooled per-lesion sensitivity was 77.1% (95%CI:73.8-80.2%). For lesions >2 cm, pooled per-lesion sensitivity was 88.5% (95%CI:85.0-91.5%). CONCLUSION: Non-contrast MRI has a moderate negative LR and high specificity with acceptable sensitivity for the detection of HCC, even in patients with cirrhosis and with lesions <2 cm. Prospective trials to validate if non-contrast MRI can be used for HCC surveillance is warranted.

Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

MRI detection of suspected nasopharyngeal carcinoma: a systematic review and meta-analysis.

PURPOSE: Endoscopic biopsy is recommended for diagnosis of nasopharyngeal carcinoma (NPC). A proportion of lesions are hidden from endoscopic view but detected with magnetic resonance imaging (MRI). This systematic review and meta-analysis investigated the diagnostic performance of MRI for detection of NPC. METHODS: An electronic search of twelve databases and registries was performed. Studies were included if they compared the diagnostic accuracy of MRI to a reference standard (histopathology) in patients suspected of having NPC. The primary outcome was accuracy for detection of NPC. Random-effects models were used to pool outcomes for sensitivity, specificity, and positive and negative likelihood ratio (LR). Bias and applicability were assessed using the modified QUADAS-2 tool. RESULTS: Nine studies were included involving 1736 patients of whom 337 were diagnosed with NPC. MRI demonstrated a pooled sensitivity of 98.1% (95% CI 95.2-99.3%), specificity of 91.7% (95% CI 88.3-94.2%), negative LR of 0.02 (95% CI 0.01-0.05), and positive LR of 11.9 (95% CI 8.35-16.81) for detection of NPC. Most studies were performed in regions where NPC is endemic, and there was a risk of selection bias due to inclusion of retrospective studies and one case-control study. There was limited reporting of study randomization strategy. CONCLUSION: This study demonstrates that MRI has a high pooled sensitivity, specificity, and negative predictive value for detection of NPC. MRI may be useful for lesion detection prior to endoscopic biopsy and aid the decision to avoid biopsy in patients with a low post-test probability of disease.

Association between serum 5-methyltetrahydrofolate and homocysteine in Chinese hypertensive participants with different MTHFR C677T polymorphisms: a cross-sectional study.

BACKGROUND AND AIMS: Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. METHODS: Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. RESULTS: There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: ß = - 0.50, P <  0.001; CC: ß = - 0.14, P = 0.087; CT: ß = - 0.20, P = 0.011; TT: ß = - 1.19, P <  0.001). Moreover, the decline in trend in genotype TT participants was stronger than in genotype CC participants (P for difference <  0.001) and genotype CT participants (P for difference <  0.001), while there was no significant difference between genotype CC and genotype CT participants (P for difference = 0.757). CONCLUSIONS: Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

Survival outcomes for surgical resection versus CT-guided percutaneous ablation for stage I non-small cell lung cancer (NSCLC): a systematic review and meta-analysis.

OBJECTIVE: Multiple cohort studies have compared surgical resection with CT-guided percutaneous ablation for patients with stage 1 non-small cell lung cancer (NSCLC); however, the results have been heterogeneous. This systematic review and meta-analysis aims to compare surgery with ablation for stage 1 NSCLC. METHOD: A search of five databases was performed from inception to 5 July 2020. Studies were included if overall survival (OS), cancer-specific survival (CSS), and/or disease-free survival (DFS) were compared between patients treated with surgical resection versus ablation (radiofrequency ablation (RFA) or microwave ablation (MWA)) for stage 1 NSCLC. Pooled odds ratios (OR) were calculated. RESULTS: A total of eight studies were included (total 792 patients: 460 resection and 332 ablation). There were no significant differences in 1- to 5-year OS or CSS between surgery versus ablation. There were significantly better 1- and 2-year DFS for surgery over ablation (OR 2.22, 95% CI 1.14-4.34; OR 2.60, 95% CI 1.21-5.57 respectively), but not 3- to 5-year DFS. Subgroup analysis demonstrated no significant OS difference between lobectomy and MWA, but there were significantly better 1- and 2-year OS with sublobar resection (wedge resection or segmentectomy) versus RFA (OR 2.85, 95% CI 1.33-6.10; OR 4.54, 95% CI 2.51-8.21, respectively). In the two studies which only included patients with stage 1A NSCLC, pooled outcomes demonstrated no significant differences in 1- to 3-year OS or DFS between surgery versus ablation. CONCLUSION: Surgical resection of stage 1 NSCLC remains the optimal choice. However, for non-surgical patients with stage 1A, ablation offers promising DFS, CSS, and OS. Future prospective randomized controlled trials are warranted. KEY POINTS: • Surgical resection of stage 1 NSCLC remains the optimal choice. • In patients with stage 1A NSCLC who are not surgical candidates, CT-guided microwave or radiofrequency ablation may be an alternative which offers promising disease-free survival and overall survival.

State-of-the-art progress of switch fluorescence biosensors based on metal-organic frameworks and nucleic acids.

Metal-organic frameworks (MOFs) have captured substantial attention of an increasing number of scientists working in sensing analysis fields, due to their large surface area, high porosity, and tunable structure. Recently, MOFs as attractive fluorescence quenchers have been extensively investigated. Given their high quenching efficiency toward the fluorescence intensity of dyes-labeled specific biological recognition molecules, such as nucleic acids, MOFs have been widely developed to switch fluorescence biosensors with low background fluorescence signal. These strategies not only lead to specificity, simplicity, and low cost of biosensors, but also possess advantages such as ultrasensitive, rapid, and multiple detection of switch fluorescence methods. At present, researches of the analysis of switch fluorescence biosensors based on MOFs and nucleic acids mainly focus on sensing of different types of in vitro and intracellular analytes, indicating their increasing potential. In this review, we briefly introduce the principle of switch fluorescence biosensor and the mechanism of fluorescence quenching of MOFs, and mainly discuss and summarize the state-of-the-art advances of MOFs and nucleic acids-based switch fluorescence biosensors over the years 2013 to 2020. Most of them have been proposed to the in vitro detection of different types of analytes, showing their wide scope and applicability, such as deoxyribonucleic acid (DNAs), ribonucleic acid (RNAs), proteins, enzymes, antibiotics, and heavy metal ions. Besides, some of them have also been applied to the bioimaging of intracellular analytes, emerging their potential for biomedical applications, for example, cellular adenosine triphosphate (ATP) and subcellular glutathione (GSH). Finally, the remaining challenges in this sensing field and prospects for future research trends are addressed. Graphical abstract.

Prognostic significance of measurable residual disease based on multiparameter flow cytometry in childhood acute myeloid leukemia. / åŸºäºŽæµå¼ç»†èƒžæœ¯çš„å¯æµ‹é‡æ®‹ç•™ç— å¯¹å„¿ç«¥æ€¥æ€§é«“ç³»ç™½è¡€ç— é¢„åŽæ„ä¹‰çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy. METHODS: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate. RESULTS: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children (P<0.05). There were no significant differences in 3-year CIR, EFS, and OS rates between the MRD-positive children with a low risk at initial diagnosis and the MRD-negative children after adjustment of chemotherapy intensity (P>0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML (P<0.05). CONCLUSIONS: MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.

Mindin serves as a tumour suppressor gene during colon cancer progression through MAPK/ERK signalling pathway in mice.

Mindin is important in broad spectrum of immune responses. On the other hand, we previously reported that mindin attenuated human colon cancer development by blocking angiogenesis through Egr-1-mediated regulation. However, the mice original mindin directly suppressed the syngenic colorectal cancer (CRC) growth in our recent study and we aimed to further define the role of mindin during CRC development in mice. We established the mouse syngeneic CRC CMT93 and CT26 WT cell lines with stable mindin knock-down or overexpression. These cells were also subcutaneously injected into C57BL/6 and BALB/c mice as well as established a colitis-associated colorectal cancer (CAC) mouse model treated with lentiviral-based overexpression and knocked-down of mindin. Furthermore, we generated mindin knockout mice using a CRISPR-Cas9 system with CAC model. Our data showed that overexpression of mindin suppressed cell proliferation in both of CMT93 and CT26 WT colon cancer cell lines, while the silencing of mindin promoted in vitro cell proliferation via the ERK and c-Fos pathways and cell cycle control. Moreover, the overexpression of mindin significantly suppressed in vivo tumour growth in both the subcutaneous transplantation and the AOM/DSS-induced CAC models. Consistently, the silencing of mindin reversed these in vivo observations. Expectedly, the tumour growth was promoted in the CAC model on mindin-deficient mice. Thus, mindin plays a direct tumour suppressive function during colon cancer progression and suggesting that mindin might be exploited as a therapeutic target for CRC.

Hidradenitis Suppurativa and Thyroid Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by painful nodules, sinus tracts, and significant scarring. Although the pathogenesis of this disease is not well established, there is increasing evidence to suggest that it is an immune-mediated disorder. Previous studies have suggested a relationship between HS and thyroid disease, which is also driven by an autoimmune process. We sought to assess whether an association exists between HS and thyroid disease. OBJECTIVES: To determine whether HS is associated with thyroid disease via meta-analysis of case-control studies. METHODS: A systematic review and meta-analysis was performed according to recommended PRISMA guidelines. Electronic searches were performed using 6 electronic databases from their inception until August 2018. Data were extracted and analyzed according to predefined clinical endpoints. Odds ratio (OR) was used as the summary effect size. RESULTS: We identified 5 case-controls studies included for meta-analysis. There were a total of 36 103 HS cases compared with 170 517 control cases. We found a significant association between HS and thyroid disease (OR 1.36, 95% CI 1.13-1.64, I 2 = 78%, P = .001). CONCLUSIONS: This pooled analysis of existing case-control studies to date supports an association between HS and any thyroid disease. Clinicians treating patients with HS should be aware of this potential association with thyroid disease.

The pattern-recognition molecule mindin binds integrin Mac-1 to promote macrophage phagocytosis via Syk activation and NF-κB p65 translocation.

Mindin has a broad spectrum of roles in the innate immune system, including in macrophage migration, antigen phagocytosis and cytokine production. Mindin functions as a pattern-recognition molecule for microbial pathogens. However, the underlying mechanisms of mindin-mediated phagocytosis and its exact membrane receptors are not well established. Herein, we generated mindin-deficient mice using the CRISPR-Cas9 system and show that peritoneal macrophages from mindin-deficient mice were severely defective in their ability to phagocytize E  coli. Phagocytosis was enhanced when E  coli or fluorescent particles were pre-incubated with mindin, indicating that mindin binds directly to bacteria or non-pathogen particles and promotes phagocytosis. We defined that 131 I-labelled mindin binds with integrin Mac-1 (CD11b/CD18), the F-spondin (FS)-fragment of mindin binds with the αM -I domain of Mac-1 and that mindin serves as a novel ligand of Mac-1. Blockade of the αM -I domain of Mac-1 using either a neutralizing antibody or si-Mac-1 efficiently blocked mindin-induced phagocytosis. Furthermore, mindin activated the Syk and MAPK signalling pathways and promoted NF-κB entry into the nucleus. Our data indicate that mindin binds with the integrin Mac-1 to promote macrophage phagocytosis through Syk activation and NF-κB p65 translocation, suggesting that the mindin/Mac-1 axis plays a critical role during innate immune responses.

Survival outcome of tonsillar squamous cell carcinoma (TSCC) in the context of human papillomavirus (HPV): A systematic review and meta-analysis.

OBJECTIVE: The objective of our study was to assess whether HPV-positive TSCC had better survival and prognosis rates, when compared to HPV-negative TSCC. METHOD: A systematic review and meta-analysis was performed comparing HPV status in TSCC patients. TSCC was confirmed with histopathology and HPV status was confirmed with PCR, immunohistochemistry and/or in-situ-hybridisation. The primary endpoints were overall survival (OS) and disease free survival (DFS). RESULTS: Twenty-four studies were identified, involving 1921 TSCC cases, of which 56.2% (1079) were HPV positive. OS was significantly higher in patients with HPV-positive compared to HPV-negative TSCC in years 1-5 (OR 2.54, P < 0.01; OR 2.93 P < 0.01; OR 2.74 P < 0.01; OR 2.20 P < 0.01, and OR 2.14 P < 0.01 respectively). Similarly, DFS was also significantly higher in patients with HPV-positive compared to HPV-negative TSCC in years 1-3 (OR 2.86, P < 0.01; OR 2.60 P < 0.02; and OR 2.60 P < 0.01 respectively), which was attenuated in years 4 and 5 (OR 1.83, P = 0.10 and OR 1.50, P = 0.12). CONCLUSION: This is the largest meta-analysis with 1921 patients, comparing non-HPV induced TSCC and HPV induced TSCC, looking at outcome and survival. HPV-positive had better OS and DFS.

Evaluation of carcinoembryonic antigen (CEA) density as a prognostic factor for percutaneous ablation of pulmonary colorectal metastases.

OBJECTIVES: To evaluate the prognostic value of carcinoembryonic antigen (CEA) density and other clinicopathological factors for percutaneous ablation of pulmonary metastases from colorectal cancer. METHODS: CEA density was calculated as: "absolute serum CEA pre-ablation/volume of all lung metastases [mm3]". Median CEA density was the cut-off for high and low groups. Cox-regression was used to determine prognostic factors for survival. RESULTS: A total of 85 patients (102 ablation sessions) were followed for a median of 27 months. High CEA density was significantly associated with worse overall survival compared to low CEA density (adjusted HR: 2.12; 95 % CI: 1.22-3.70, p=0.002; median survival: 25.7 vs. 44.3 months). The interval between primary resection of the colorectal carcinoma and first ablation was also a prognostic factor, a duration >24 months being associated with better survival compared to a shorter interval (0-24 months) (adjusted HR: 0.55; 95 % CI: 0.31-0.98, p=0.04). Moreover, a disease-free interval >24 months was significantly associated with low CEA density compared to a shorter interval (0-24 months) (adjusted OR: 0.29; 95 % CI: 0.11-0.77, p=0.01). CONCLUSIONS: Serum CEA density and interval between primary resection of a colorectal carcinoma and pulmonary ablation are independent prognostic factors for overall survival. In two patients with identical CEA serum levels, the patient with the lower/smaller pulmonary tumour load would have a worse prognosis than the one with the higher/larger pulmonary metastases. KEY POINTS: • CEA density is an independent prognostic factor for colorectal pulmonary metastases. • A lower CEA density is associated with better overall survival. • CEA may play a functional role in tumour progression. • High CEA density is associated with smaller tumours. • Interval between pulmonary ablation and primary colorectal carcinoma is a prognostic factor.

The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia, Lewy body dementia, and Alzheimer's disease: clinical experience in China.

BACKGROUND AND AIMS: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia. METHOD: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI). RESULTS: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients. CONCLUSION: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.

Impacts of Preoperative Serum Albumin Level on Outcomes of Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy.

BACKGROUND: Only few small studies in the literature have explored the impacts of preoperative serum albumin level and clinical outcomes of patients with peritoneal surface malignancy (PSM) who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). This study aimed to evaluate the value of preoperative serum albumin as a prognostic factor for long-term survival outcomes after CRS and PIC in a large patient cohort and to determine whether preoperative serum albumin is correlated with perioperative complications. METHODS: This retrospective study examined prospectively collected data for patients with PSM who underwent CRS and PIC by one surgical team at St George Hospital in Sydney, Australia. The study used 35 g/L as the cuffoff for normal serum albumin level. RESULTS: The study enrolled 591 patients. Hypoalbuminemia was found to be associated with a significantly higher rate of major morbidity (p < 0.001), a longer ICU stay (p = 0.003), a longer HDU stay (p < 0.001), a longer total hospital stay (p < 0.001), and a shorter overall survival (OS) (p = 0.016). Factor analysis showed preoperative serum hypoalbuminemia to be a prognostic factor for a poor perioperative outcome (p = 0.018) and a poor OS (p = 0.026). CONCLUSION: Preoperative hypoalbuminemia is associated with poor perioperative outcomes. More importantly, it is a predictor of poorer OS for patients with PSM independent of the PCI, age, and completeness of cytoreduction. In the future, strategies should be undertaken to improve preoperative nutrition of malnourished patients as a means of improving clinical outcomes for patients with PSM.

Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality.

BACKGROUND AND PURPOSE: Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality. METHODS: A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months. RESULTS: During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 µmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03-2.53) compared with patients in the lowest quartile (≤10 µmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05-3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30-2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06-4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01-4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels. CONCLUSIONS: Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype.