Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.

Revealing Metabolic Dysregulation Induced by Polypropylene Nano- and Microplastics in Nile Tilapia via Noninvasive Probing Epidermal Mucus.

A noninvasive sampling technology was conceived, employing a disposable acupuncture needle in conjunction with high-resolution mass spectrometry (termed as noninvasive direct sampling extractive electrospray ionization mass spectrometry, NIDS-EESI-MS) to scrutinize the epidermal mucus of Nile tilapia for insights into the metabolic dysregulation induced by polypropylene nano- and microplastics. This analytical method initiates with the dispensing of an extraction solvent onto the needles coated with the mucus sample, almost simultaneously applying a high voltage to generate analyte ions. This innovative strategy obliterates the necessitation for laborious sample preparation, thereby simplifying the sampling process. Employing this technique facilitated the delineation of a plethora of metabolites, encompassing, but not confined to, amino acids, peptides, carbohydrates, ketones, fatty acids, and their derivatives. Follow-up pathway enrichment analysis exposed notable alterations within key metabolic pathways, including the biosynthesis of phenylalanine, tyrosine, and tryptophan, lysine degradation, as well as the biosynthesis and metabolism of valine, leucine, and isoleucine pathways in Nile tilapia, consequent to increased concentrations of polypropylene nanoplastics. These metabolic alterations portend potential implications such as immune suppression, among other deleterious outcomes. This trailblazing application of this methodology not only spares aquatic life from sacrifice but also inaugurates an ethical paradigm for conducting longitudinal studies on the same organisms, facilitating detailed investigations into the long-term effects of environmental pollutants. This technique enhances the ability to observe and understand the subtle yet significant impacts of such contaminants over time.

Prognostic value of 18F-FDG PET/CT in malignant pleural mesothelioma: a meta-analysis.

BACKGROUND: Several FDG PET/CT parameters have been utilized to evaluate the prognosis in malignant pleural mesothelioma (MPM). However, there are still controversial results due to the low incidence of MPM. PURPOSE: To assess the prognostic value of 18F-FDG PET/CT in MPM. MATERIAL AND METHODS: A systematic literature search was performed in PubMed, Embase, Medline, and The Cochrane Library to identify eligible studies from inception to 12 February 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of several variables, such as maximum standardized uptake value (SUVmax), the reduction of SUVmax after treatment (ΔSUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and the reduction of TLG after treatment (ΔTLG), were calculated. Meta-regression with subsequent subgroup analyses were conducted to determine the heterogeneity of cutoff values, treatment regimen, study design, uptake time, and scanners across various studies. RESULTS: In total, 19 eligible studies including 1819 patients were enrolled in the meta-analysis. The univariate analysis showed that the pooled HRs (95% CI) of SUVmax, ΔSUVmax, MTV, TLG, and ΔTLG were 1.29 (1.16-1.42), 1.12 (1.05-1.19), 1.15 (1.00-1.33), 1.47 (1.23-1.76), and 1.27 (1.12-1.45), respectively. The multivariate analysis showed that the pooled HRs (95% CI) of SUVmax, ΔSUVmax, MTV, and TLG for overall survival (OS) were 1.20 (1.08-1.33), 1.10 (1.02-1.19), 0.95 (0.81-1.11), and 1.13 (1.08-1.18), respectively. CONCLUSION: SUVmax, ΔSUVmax, TLG, and ΔTLG are significant prognostic indicators for OS, while more clinical studies are needed to confirm the prognostic value of MTV in MPM.

Pathogenesis and Therapeutic Targets of Focal Cortical Dysplasia Based on Bioinformatics Analysis.

Focal cortical dysplasia (FCD), a malformation of cortical development, is the most common cause of intractable epilepsy in children. However, the causes and underlying molecular events of FCD need further investigation. The microarray dataset GSE62019 and GSE97365 were obtained from Gene Expression Omnibus. To examine critical genes and signaling pathways, bioinformatics analysis tools such as protein-protein interaction (PPI) networks, miRNA-mRNA interaction networks, and immune infiltration in FCD samples were used to fully elucidate the pathogenesis of FCD. A total of 534 differentially expressed genes (DEGs) and 71 differentially expressed miRNAs (DEMs) were obtained. The DEGs obtained were enriched in ribosomal, protein targeting, and pathways of neurodegeneration multiple diseases, whereas the target genes of DEMs were enriched in signaling pathways such as transforming growth factor beta, Wnt, PI3K-Akt, etc. Finally, four hub genes (RPL11, FAU, RPS20, RPL27) and five key miRNAs (hsa-let-7b, hsa-miR-185, hsa-miR-23b, hsa-miR-222 and hsa-miR-92b) were obtained by PPI network, miRNA-mRNA network, and ROC analysis. The immune infiltration results showed that the infiltration levels of five immune cells (MDSC, regulatory T cells, activated CD8+ T cells, macrophage and effector memory CD8+ T cells) were slightly higher in FCD samples than in control samples. Moreover, the gene expressions of RPS19, RPL19, and RPS24 were highly correlated with the infiltration levels and immune characteristics of 28 immune cells. It broadens the understanding of the molecular mechanisms underlying the development of FCD and enlightens the identification of molecular targets and diagnostic biomarkers for FCD.

Identification and determination of structurally related peptide impurities in thymalfasin by liquid chromatography-high-resolution mass spectrometry.

Thymalfasin is an important peptide drug widely used for the single or combination treatment of hepatitis, sepsis, cancer, and immunodeficiency. Accurate purity assessment of thymalfasin material is essential for thymalfasin certified reference materials (CRMs) production and analytical method validation, in which comprehensive determination of thymalfasin-related impurities is required to avoid quantitative bias. In this study, liquid chromatography-high-resolution mass spectrometry (LC-hrMS) methods have been established to comprehensively characterize and quantify thymalfasin-related impurities using a thymalfasin China Pharmacopoeia (ChP) standard and then successfully applied to three commercial thymalfasin materials. A total of twenty-three thymalfasin-related impurities (> 0.1 mg/g) were separated, identified, and quantified in the ChP standard analyzed. The major impurities existing in thymalfasin ChP standard and commercial materials include deamination, amination, succinimide, amino acid insertion/deletion, dimers, and isomers at different mass fraction levels. In particular, over half of the thymalfasin-related impurities were found directly or indirectly arising from the labile C-terminal asparagine (Asn) residue. Given the 28th Asn residue at the C-terminus is not necessary for the biological activity of thymalfasin as reported previously, thus deletion, replacement, or modification of thymalfasin C-terminal Asn residue is proposed for new drug research and development. In summary, these results provide a further complement to the thymalfasin-related impurity profile and issue a warning for protection or processing of the thymalfasin C-terminal Asn residue.

Clinical value of 68Ga-DOTA-SSTR PET/CT in the diagnosis and detection of neuroendocrine tumors of unknown primary origin: a systematic review and meta-analysis.

BACKGROUND: The ability of 68Ga-DOTA-SSTR to detect the primary sites of neuroendocrine tumors (NETs) remains undetermined, and the clinical benefit of this imaging agent is not clear. PURPOSE: To evaluate the diagnostic accuracy of 68Ga-DOTA-SSTR for carcinoma unknown primary (CUP) neuroendocrine tumors and to further analyze the detection rate of 68Ga-DOTA-SSTR for primary and metastatic sites. MATERIAL AND METHODS: A comprehensive literature search of PubMed/MEDLINE and ScienceDirect was performed in October 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We critically reviewed all studies based on the PICOS criteria. QUADAS-2 was used to evaluate the quality of the methodology of the included studies. RESULTS: A total of 10 studies (484 patients, mean age = 56.6 ± 4.3 years) were included in the study. The pooled sensitivity and specificity of 68Ga-DOTA-SSTR in identifying CUP-NETs were 82% and 55%, respectively. The area under the receiver operating characteristic curve was 69%. Regarding metastasis sites, 68Ga-DOTA-SSTR found the most metastases in the liver (57.9%), followed by the lymph nodes (22.8%), bones (12.8%), lung (2.8%), and others (1.7%). The pooled detection rate of 68Ga-DOTA-SSTR for CUP-NETs was 61%. CONCLUSION: The present study demonstrated the high diagnostic sensitivity of 68Ga-DOTA-SSTR for CUP-NETs. 68Ga-DOTA-SSTR PET/CT was highly effective in locating the primary and metastatic sites of CUP-NETs.

Impurity identification and quantification for arginine vasopressin by liquid chromatography/high-resolution mass spectrometry.

RATIONALE: For pharmaceutical quality control, impurities may have unexpected pharmacological or toxicological effects on quality, safety, and efficacy of drugs. Arginine vasopressin (AVP) is an important cyclic peptide drug that is mainly used for the treatment of diabetes insipidus and esophageal varices bleeding. With the advancement made in analytical techniques, liquid chromatography/high-resolution mass spectrometry (LC/HRMS) has emerged as a critical technique for the identification and quantification of structurally related peptide impurities in AVP. METHODS: An LC/HRMS/MS-based method using a quadrupole ion trap-Orbitrap mass spectrometer operated in the positive ion electrospray ionization mode was developed for the determination and quantification of structurally related peptide impurities in AVP. RESULTS: Under optimized experimental conditions, three deamidation products, ([Glu4 ]AVP, [Asp5 ]AVP, and AVP acid), two amino acid deletion impurities (des-Pro7 -AVP and des-Gly9 -AVP), one amino acid insertion impurity (endo-Gly10a -AVP), one end chain reaction product (N-acetyl-AVP), and one AVP isomer were detected. Subsequent quantification using an external standard method estimated the total mass fraction of all structurally related peptide impurities in the AVP study material to be 30.3 mg/g with an expanded uncertainty of 3.0 mg/g (k = 2). CONCLUSIONS: This study complements the AVP impurity profile and improves the separation and discovery of other potential impurities in vasopressin analogues.

The impact of sedation on quality metrics of colonoscopy: a single-center experience of 48,838 procedures.

PURPOSE: Investigation of the role of sedation during colonoscopy is meaningful as the advantages of colonoscopy performing with sedation are still controversial. METHODS: Medical records of patients who underwent colonoscopy in our institution were retrospectively analyzed. The sedation rate, adenoma detection rate (ADR), polyp detection rate (PDR), cecal intubation rate (CIR), iatrogenic colonic perforation rate (ICP) were calculated. RESULTS: A total of 48,838 colonoscopies (24,498 in males) dated from July 2007 to February 2017 were analyzed. The median age was 50 years (range 16-85 years). An overall sedation rate was 80.38%. The PDR was 26.77%, and was not statistically different between colonoscopy with or without sedation (26.67% vs 27.22, p = 0.474). ADR was 12.9% regardless of applying sedation or not (13.0% vs 12.44%, p = 0.337). The CIR was 87.42% in all examinations with an adjusted CIR of 90.34%, and was higher when performed with sedation than without sedation (88.92% vs 80.64%, p < 0.0001). Five cases (0.01%) of ICP were reported, all of which occurred in patients under sedation. CONCLUSIONS: The use of sedation is associated with increased CIR, but ADR and PDR remain unchanged with or without sedation. However, perforation rate, albeit very low, is significantly higher in sedated patients.

Contribution of 18F-FDG PET/CT in a case-mix of fever of unknown origin and inflammation of unknown origin: a meta-analysis.

BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are challenging medical problems. Previous studies have shown that 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) plays an important role in the diagnosis of FUO, but few studies have explored this diagnostic technique in relation to IUO. PURPOSE: To systematically review and perform a meta-analysis of published data on the diagnostic performance of PET/CT in the diagnosis of FUO and IUO. MATERIAL AND METHODS: A comprehensive literature search was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines published in March 2018. Meta-analysis of diagnostic performance was performed using STATA 12.0 software. Subgroup analysis was performed by stratification based on study design, number of patients, geographic area, and final diagnosis based on 18F-FDG PET/CT. Meta-regression analyses were performed to recognize heterogeneity. RESULTS: Our meta-analysis included 23 studies, comprising a total sample size of 1927 patients. The pooled diagnosis performance was calculated with a per-patient-based analysis: sensitivity = 0.84 (95% confidence interval [CI] = 0.79-0.89), specificity = 0.63 (95% CI = 0.49-0.75), positive likelihood ratio = 2.3 (95% CI = 1.5-3.4), negative likelihood ratio = 0.25 (95% CI = 0.16-0.38), diagnostic odds ratio = 9 (95% CI = 4.0-20), and AUC = 0.84 (95% CI = 0.81-0.87). CONCLUSION: In patients with non-specific symptoms and signs, 18F-FDG PET/CT is very helpful for recognizing and excluding diseases, directing further diagnostic decisions, and avoiding unnecessary invasive examinations. We recommend that 18F-FDG PET/CT should be considered among the first-line diagnostic tools for patients with FUO and IUO.

68Ga-somatostatin receptor analogs and 18F-FDG PET/CT in the localization of metastatic pheochromocytomas and paragangliomas with germline mutations: a meta-analysis.

BACKGROUND: Metastatic pheochromocytoma and paraganglioma (PCs/PGLs) show high germline mutation, and 18F-FDG and 68Ga-DOTA peptide positron emission tomography/computed tomography (PET/CT) imaging are recommended for the diagnosis of metastatic of PCs. However, there has been lack of direct comparison of the two modalities in the diagnosis of metastatic of PCs up to now. PURPOSE: To evaluate and compare the value of localization of 68Ga-somatostatin receptor analogs and 18F-FDG in the diagnosis of metastatic PCs/PGLs. MATERIAL AND METHODS: A comprehensive literature search of PubMed/MEDLINE, ScienceDirect, and Web of Science was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines published in August 2016. We critically reviewed all studies based on the PICOS criteria. QUADAS-2 was used to evaluate the quality of the methodology of the included studies. RESULTS: This meta-analysis included 17 studies (629 patients, average age [mean ± SD] = 42.7 ± 6.3 years). The pooled sensitivity and specificity of 18F-FDG and 68Ga peptides were 0.85 (95% confidence interval [CI] = 0.78-0.91) and 0.55 (95% CI = 0.37-0.73), and 0.95 (95% CI = 0.92-0.97) and 0.87 (95% CI = 0.63-0.96), respectively. The area under the sROC curves of the 18F-FDG and 68Ga peptides were 0.88 (95% CI = 0.85-0.91) and 0.78 (95% CI = 0.74-0.81), respectively. A subgroup analysis demonstrated that the difference at the per-lesion level and gene mutation level was significant. CONCLUSION: Compared to 18F-FDG PET/CT, the 68Ga-somatostatin receptor demonstrated good performance in the localization of metastatic PCs/PGLs, especially those with germline mutations. The use of the 68Ga-somatostatin receptor can be a new tool in the diagnosis of metastatic PCs/PGLs.

The diagnostic value of 11C-methionine PET in hyperparathyroidism with negative 99mTc-MIBI SPECT: a meta-analysis.

Background 99mTc-sestamibi (MIBI) parathyroid SPECT is generally regarded as the best preoperative localizing method in patients with hyperparathyroidism (HPT). However, 99mTc-MIBI SPECT is false negative in approximately 25% of adenomas. 11C-methionine positron emission tomography (PET) has been used in HPT with negative 99mTc-MIBI SPECT scan results. Purpose To systematically review and conduct a meta-analysis of published data on the performance of 11C-methionine PET in patients with HPT with negative 99mTc-MIBI SPECT. Material and Methods A comprehensive review of the literature was performed. Pooled sensitivity and specificity of 11C-methionine PET in patients with HPT and a negative 99mTc-MIBI SPECT was calculated on a per-patient basis using receiver-operating characteristic (ROC) methodology. Results Nine studies that met all inclusion and exclusion criteria were included into our meta-analysis, comprising a total sample size of 137 patients. Pooled sensitivity and specificity of 11C-methionine PET in patients with HPT with negative or inconclusive 99mTc-MIBI SPECT scans was 86% and 86%, respectively. The area under the ROC curve was 0.87. Conclusion By merit of the high overall sensitivity, specificity, and accuracy, 11C-methionine PET can potentially complement the diagnostic workup of patients with HPT and negative or inconclusive 99mTc-MIBI SPECT. 11C-methionine PET appears to be a promising diagnostic modality in complicated cases with HPT.

The accuracy of V/Q SPECT in the diagnosis of pulmonary embolism: a meta-analysis.

BACKGROUND: Ventilation perfusion single photon emission computed tomography (V/Q SPECT) and CT pulmonary angiography have all been used in the diagnosis of acute PE. Previous studies have shown higher sensitivity and specificity and a marked decrease in the non-diagnostic rate of V/Q SPECT than planar scan. PURPOSE: To systematically review and perform a meta-analysis of published data on the performance of V/Q SPECT in the diagnosis of acute PE. MATERIAL AND METHODS: A comprehensive computer search was conducted on literature published through 31 December 2013 in an effort to find relevant articles on the diagnostic performance of V/Q SPECT in the diagnosis of PE patients. Pooled sensitivity, specificity, negative likelihood ratio (LR), and positive LR, the area under the receiver-operating characteristic (ROC) curve of V/Q SPECT in the diagnosis of PE patients were calculated. RESULTS: Nine studies, comprising a total sample size of 3454 patients, were included in our meta-analysis. The pooled sensitivity, specificity of V/Q SPECT in the diagnosis of acute PE patients, calculated on a per-patient-based analysis, was 96% (95% confidence interval [CI], 95-97%), 97% (95% CI, 96-98%). The pooled negative LR, positive LR of V/Q SPECT in acute PE patients was 0.06 (range, 0.02-0.19) and 16.64 (range, 9.78-31.54). The area under the ROC curve of V/Q SPECT in the diagnosis of acute PE patients was 0.99 on a per-patient-based analysis. CONCLUSION: V/Q SPECT is an accurate method in acute PE patients with high sensitivity and high specificity in the diagnosis of PE.

Highly sensitive and selective strategy for microRNA detection based on WS2 nanosheet mediated fluorescence quenching and duplex-specific nuclease signal amplification.

MicroRNAs (miRNAs) play vital roles in physiologic and pathologic processes and are significant biomarkers for disease diagnostics and therapeutics. However, rapid, low-cost, sensitive, and selective detection of miRNAs remains a challenge because of their short length, sequence homology, and low abundance. Herein, we report for the first time that WS2 nanosheet can exhibit differential affinity toward short oligonucleotide fragment versus ssDNA probe and act as an efficient quencher for adsorbed fluorescent probes. This finding is utilized to develop a new strategy for simple, sensitive, and selective detection of miRNA by combining WS2 nanosheet based fluorescence quenching with duplex-specific nuclease signal amplification (DSNSA). This assay exhibits highly sensitive and selective with a detection limit of 300 fM and even discriminate single-base difference between the miRNA family members. The result indicates that this simple and cost-effective strategy holds great potential application in biomedical research and clinical diagnostics.

Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis.

BACKGROUND: Gallium-68 somatostatin receptor positron emission tomography (PET) has been used in the diagnosis of neuroendocrine tumors (NETs). The compounds often used in molecular imaging of NETs with PET are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. There is varying affinity to different somatostatin receptors. PURPOSE: To systematically review and perform a meta-analysis of published data regarding the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. MATERIAL AND METHODS: A comprehensive literature search of studies published through 30 April 2013 regarding 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs was performed using the PubMed/MEDLINE, Embase, and Scopus databases. Pooled sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. RESULTS: Ten studies comprising 416 patients with NETs were included in this meta-analysis. The pooled sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs calculated on a per-patient-based analysis was 93% (95% confidence interval [CI] 89-96%) and 96% (95% CI 91-99%). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing NETs was 85% (95% CI 74-93%) and 100% (95% CI 82-100%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98, respectively, on a per-patient-based analysis. CONCLUSION: The molecular imaging agents 68Ga-DOTATOC and 68Ga-DOTATATE demonstrated high sensitivity and specificity in the diagnosis of NETs on PET scan. Although both are accurate tools in the diagnosis of NETs, 68Ga-DOTATATE PET may be more sensitive and specific than 68Ga-DOTATOC PET scan.

The role of 18F-FDG PET/CT metabolic parameters in the differential diagnosis of post-transplant lymphoproliferative disorder after pediatric liver transplantation.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a significant complication after liver transplantation. Research on the diagnostic value of the Fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) metabolic parameters of PTLD in pediatric liver transplantation (pLT) recipients is limited. This study sought to evaluate the diagnostic efficacy of 18F-FDG PET/CT in differentiating between PTLD and non-PTLD lymphadenopathy in pLT recipients. Methods: This retrospective study collected the 18F-FDG PET/CT scans with clinical and pathological information of all consecutive children who were clinically suspected of PTLD from November 2016 to September 2022 at the Beijing Friendship Hospital. The 18F-FDG PET/CT metabolic parameters of the two groups were analyzed. We then established a diagnostic model composed of the clinical characteristics and metabolic parameters. Results: In total, 57 eligible patients were enrolled in this study, of whom 40 had PTLD and 17 had non-PTLD lymphadenopathy. Of the metabolic parameters examined in this study, total lesion glycolysis (TLG) had the highest area under the curve (AUC) value [0.757, 95% confidence interval (CI): 0.632-0.883, P=0.002]. The AUCs of the other metabolic parameters were all less than the AUC of TLG, including the maximum standardized uptake value (SUVmax) (AUC: 0.725, 95% CI: 0.597-0.853, P=0.008), mean standardized uptake value (SUVmean) (AUC: 0.701, 95% CI: 0.568-0.834, P=0.017), metabolic tumor volume total (MTVtotal) (AUC: 0.688, 95% CI: 0.549-0.827, P=0.040), TLG total (AUC: 0.674, 95% CI: 0.536-0.812, P=0.026). The diagnostic model, which was composed of clinical characteristics (digestive symptoms), the SUVmax, TLG, and the MTVtotal, showed excellent performance in the differential diagnosis (sensitivity: 0.675, 95% CI: 0.508-0.809; specificity: 0.941, 95% CI: 0.692-0.997; positive predictive value: 0.964, 95% CI: 0.798-0.998; and negative predictive value: 0.552, 95% CI: 0.360-0.730). Conclusions: The 18F-FDG PET/CT metabolic parameters can be used to distinguishing between PTLD and non-PTLD lymphadenopathy in pLT recipients.

Splenic Pseudoprogression After CAR-T Therapy Detected by 18 F-FDG PET/CT in a Refractory Diffuse Large B-Cell Lymphoma Patient.

ABSTRACT: A 43-year-old woman diagnosed with refractory diffuse large B-cell lymphoma was referred to chimeric antigen receptor T-cell therapy at our institution. After 3 cycles of bridging therapy, preinfusion 18 F-FDG PET/CT suggested a complete metabolic response. 18 F-FDG PET/CT 1 month after chimeric antigen receptor T-cell infusion showed 2 foci of elevated activity in the spleen, which was finally confirmed as pseudoprogression.

Overview of the current procedures in synthesis of heparin saccharides.

Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 â†’ 4 glycosidic bonds, is the most widely used anticoagulant. To subvert the dependence on animal sourced heparin, alternative methods to produce heparin saccharides, i.e., either heterogenous sugar chains similar to natural heparin, or structurally defined oligosaccharides, are becoming hot subjects. Although the success by chemical synthesis of the pentasaccharide, fondaparinux, encourages to proceed through a chemical approach generating homogenous product, synthesizing larger oligos is still cumbersome and beyond reach so far. Alternatively, the chemoenzymatic pathway exhibited exquisite stereoselectivity of glycosylation and regioselectivity of modification, with the advantage to skip the tedious protection steps unavoidable in chemical synthesis. However, to a scale of drug production needed today is still not in sight. In comparison, a procedure of de novo biosynthesis in an organism could be an ultimate goal. The main purpose of this review is to summarize the current available/developing strategies and techniques, which is expected to provide a comprehensive picture for production of heparin saccharides to replenish or eventually to replace the animal derived products. In chemical and chemoenzymatic approaches, the methodologies are discussed according to the synthesis procedures: building block preparation, chain elongation, and backbone modification.

Diagnostic Role of FDG PET/CT in Pediatric Patients With Chronic Recurrent Multifocal Osteomyelitis.

PURPOSE: Chronic recurrent multifocal osteomyelitis (CRMO), or chronic nonbacterial osteomyelitis, is difficult to diagnose. The accurate diagnosis of CRMO relies on comprehensive imaging examinations because of its multifocal nature. In this regard, 18 F-FDG PET/CT has demonstrated significant utility in inflammatory diseases. This study tries to determine the value of FDG PET/CT in the evaluation of CRMO. PATIENTS AND METHODS: We retrospectively collected imaging data from pediatric CRMO patients who underwent FDG PET/CT scans. Lesions exhibiting abnormal metabolism with/without structural abnormalities on FDG PET/CT were identified as CRMO lesions, and their location and SUV max were recorded. RESULTS: A total of 21 pediatric patients with CRMO were included in this study. The median age at diagnosis was 9.4 years. Total 131 foci of abnormal activity were identified using FDG PET/CT imaging. The distribution pattern showed a higher prevalence of lower limbs and pelvis involvement. Among all identified lesions, abnormalities were detected on both PET and CT images of 93 lesions, whereas exclusively positive findings on 18 F-FDG PET alone were observed for 38 of them. CONCLUSIONS: Our study findings suggest a higher prevalence of lesions in the bones of the lower limbs and pelvis among children with CRMO. Compared with CT scans, FDG PET exhibits superior sensitivity in detecting these lesions.

Predictive value of 2-deoxy-2-fluorine-18-fluoro-D-glucose positron emission tomography/computed tomography parameters for MYCN amplification in high-risk neuroblastoma.

OBJECTIVES: To investigate the predictive value of 2-deoxy-2-fluorine-18-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters for MYCN amplification in high-risk neuroblastoma (HR-NB). MATERIALS AND METHODS: A retrospective analysis was performed by reviewing 68 HR-NB patients who underwent MYCN testing and 18F-FDG PET/CT imaging at our hospital between January 2018 and December 2019. Based on the results of MYCN testing, patients were categorized into either the MYCN-amplified (MNA) or MYCN non-amplified (MYCN-NA) group. The 18F-FDG PET/CT parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), tumor metabolic volume (MTV), total lesion glycolysis (TLG), coefficient of variation (COV), and areas under the curve of cumulative SUV-volume histogram index (AUC-CSH index) were evaluated. Independent predictors were identified through univariate and multivariate logistic regression analyses, and their diagnostic performance was evaluated using the receiver-operating characteristic (ROC) curve. RESULTS: Univariate logistic regression analysis revealed that SUVpeak was significantly associated with MYCN amplification. Multivariate logistic regression analysis showed that SUVpeak was an independent predictor of MYCN amplification in HR-NB [Odds ratio (OR) = 0.673, 95 % confidence interval (95 % CI): 0.494-0.917, P = 0.012]. ROC curve analysis demonstrated that the predictive model including SUVpeak had higher diagnostic performance [area under the curve (AUC): 0.790, 95 % CI: 0.677-0.881, sensitivity: 0.861, specificity: 0.591, positive predictive value (PPV): 0.820, negative predictive value (NPV): 0.722] compared to using SUVpeak alone (AUC: 0.640, 95 % CI: 0.514-0.752, sensitivity: 0.630, specificity: 0.682, PPV: 0.806, NPV: 0.469). CONCLUSION: SUVpeak can predict the MYCN amplification in HR-NB patients. The predictive model constructed by combining SUVpeak and age can distinguish MYCN status in HR-NB non-invasively with superior efficacy compared to using SUVpeak alone.

Preoperative metabolic parameters of 18F-FDG PET/CT are associated with TNM stage and prognosis of colorectal cancer patients.

Background: Colorectal cancer (CRC) is the third most frequent cause of cancer-related death, while tumor/node/metastasis (TNM) stage of American Joint Committee on Cancer is the guideline of making treatment strategy and predicting survival. The aim of this study is to investigate the association of preoperative 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), TNM stage, and prognosis of patients with CRC. Methods: From September 2016 to August 2022, a total of 132 patients were retrospectively and consecutively enrolled in this cross-sectional study, who were diagnosed as CRC by histopathology and received preoperative 18F-FDG PET/CT. Firstly, the correlation between the metabolic parameters and clinicopathological features of the primary tumors was investigated. Secondly, univariate and multivariate logistic regression analyses were used to estimate the odds ratio of the association between the clinical and metabolic parameters and the advanced TNM stage (stage III-IV). Thirdly, progression-free survival (PFS) was analyzed using Kaplan-Meier curves and Log-rank test. Results: The results revealed that the metabolic tumor volume (MTV) >6.6 cm3 and serum carcinoembryonic antigen (CEA) >5.84 ng/mL were independently associated with advanced TNM stage (P=0.0009, 0.0011, respectively). Larger tumor size, higher tumor-to-liver standardized uptake value ratio, MTV, and total lesion glycolysis (TLG) were significantly correlated with advanced pT stage (stage 4), and higher TLG and MTV were significantly correlated with advanced pN stage (stage 1-2) (P<0.05), while no metabolic parameters were significantly correlated with metastasis status (P>0.05). Higher serum CEA and carbohydrate antigen 19-9 levels were significantly correlated with advanced pT, pN stage, and metastasis status (P<0.05). Patients were followed up for at least 1 year. The MTV >6.6 cm3 was significantly associated with worse PFS (P=0.032). Conclusions: 18F-FDG PET-CT can serve as a noninvasive tool for preoperatively staging CRC. The MTV >6.6 cm3 might be associated with advanced TNM stage and worse PFS.