Metabolic reprogramming of immune cells following vaccination: from metabolites to personalized vaccinology

Identifying metabolic signatures induced by the immune response to vaccines allows to discriminate vaccinated from non-vaccinated subjects and decipher the molecular mechanisms associated with the host immune response. This review illustrates and discusses the results of metabolomics-based studies on the innate and adaptive immune response to vaccines, long-term functional reprogramming (immune memory), and adverse reactions. Glycolysis is not overexpressed by vaccines, suggesting that the immune cell response to vaccinations does not require rapid energy availability as that is necessary during an infection. Vaccines strongly impact lipids metabolism, including saturated or unsaturated fatty acids, inositol phosphate, and cholesterol. Cholesterol is strategic for synthesizing 25-hydroxycholesterol in activated macrophages and dendritic cells and stimulates the conversion of macrophages and T cells in M2 macrophage and Treg, respectively. In conclusion, the large-scale application of metabolomics enables the identification of candidate predictive biomarkers of vaccine efficacy/tolerability

Quality of Life in Patients Treated with Percutaneous Laser Ablation for Non-Functioning Benign Thyroid Nodules: A Prospective Single-Center Study

Objective: While many studies have reported that laser ablation (LA) for benign non-fuctioning thyroid nodules is efficacious in reducing nodular volume and neck symptoms, none have described changes in quality of life (QoL). The purpose of this study was to report post-LA changes in QoL in our cohort of patients. Materials and Methods: Fourteen patients with benign thyroid nodules were involved in a prospective, single-center study and underwent a single session of LA. We evaluated the following: changes in nodule volume, thyroid function, and autoimmunity; adverse events during and after LA; changes in neck discomfort by means of a visual analogic scale (VAS) at one week and 1, 3, 6, and 12 months; and changes in QoL through the 13-scale Thyroid-specific Patient Reported Outcome (ThyPRO) questionnaire at 1, 3, 6, and 12 months. ThyPRO is a validated questionnaire for thyroid diseases, which consists of 13 scales with multiple-choice answers. They investigate several aspects of life that may be impaired by goiter-related compression symptoms, by esthetic alterations and by hypo- or hyperthyroidism. Results: Nodule volume decrease was -37 \ub1 23%, -55 \ub1 22%, -53 \ub1 25%, -58 \ub1 25% (p < 0.01 vs. baseline) at the first, third, sixth, and twelfth month, respectively. No hypothyroidism or positivization of autoimmunity was observed. There were no major complications during or after LA. After LA, VAS scores improved significantly from 1 week onwards in 100% of patients, while a significant improvement was seen in the goiter symptoms score after one month, and in the general score and mean values of ThyPRO after six months. Scores on the other ThyPRO scales did not change significantly. Conclusion: Laser ablation is safe and effective in reducing nodule volume and neck symptoms; this is confirmed by improvements in the goiter scale, general score, and mean values of ThyPRO and in the VAS score

Diagnostic value of soluble CD14 subtype (sCD14-ST) presepsin for the postmortem diagnosis of sepsis-related fatalities

The first aim of this study was to assess the diagnostic performance of presepsin (sCD14-ST) in postmortem serum from femoral blood compared to procalcitonin (PCT) to detect sepsis-related fatalities. The second aim was to compare sCD14-ST levels found in postmortem serum to the values in pericardial fluid to investigate the usefulness of the latter as an alternative biological fluid. Two study groups were formed, a sepsis-related fatalities group and a control group. Radiology (unenhanced CT scans and postmortem angiographies), autopsies, histology, neuropathology, and toxicology as well as other postmortem biochemistry investigations were performed in all cases. Microbiological investigations on right cardiac blood were carried out exclusively in septic cases. The results of this study indicated that postmortem serum PCT and sCD14-ST levels, individually considered, allowed septic cases to be identified. Even though increases in both PCT and sCD14-ST concentrations were observed in the control cases, coherent PCT and sCD14-ST results in cases with suspected sepsis allowed the diagnosis to be confirmed. Conversely, no relevant correlation was identified between postmortem serum and pericardial fluid sCD14-ST levels in either the septic or control group

Metabolomics: a challenge for detecting and monitoring inborn errors of metabolism

Timely newborn screening and genetic profiling are crucial in early recognition and treatment of inborn errors of metabolism (IEMs). A proposed nosology of IEMs has inserted 1,015 well-characterized IEMs causing alterations in specific metabolic pathways. With the increasing expansion of metabolomics in clinical biochemistry and laboratory medicine communities, several research groups have focused their interest the analysis of metabolites and their interconnections in IEMs. Metabolomics has the potential to extend metabolic information, thus allowing to achieve an accurate diagnosis for the individual patient and to discover novel IEMs. Structural and functional information on 247 metabolites associated with 147 IEMs and 202 metabolic pathways involved in various IEMs have been reported in the human metabolome data base (HMDB). For each metabolic gene, a new computational approach can be developed for predicting a set of metabolites, whose concentration is predicted to change after gene knockout in urine, blood and other biological fluids. Both targeted and untargeted mass spectrometry (MS)-based metabolomic approaches have been used to expand the range of disease-associate metabolites. The quantitative targeted approach, in conjunction with chemometrics, can be considered a basic tool for validating known diagnostic biomarkers in various metabolic disorders. The untargeted approach broadens the identification of new biomarkers in known IEMs and allows pathways analysis. Urine is an ideal biological fluid for metabolomics in neonatology; however, lack of standardization of preanalytical phase may generate potential interferences in metabolomic studies. The integration of genomic and metabolomic data represents the current challenge for improving diagnosis and prognostication of IEMs. The goals consist in identifying both metabolically active loci and genes relevant to a disease phenotype, which means deriving disease-specific biological insights

Metabolomic Studies in Inborn Errors of Metabolism: Last Years and Future Perspectives

The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are not covered in newborn screening and the diagnostic profiling in the metabolic laboratory is indispensable to reach a correct diagnosis. In recent years, Metabolomics helped to obtain a better understanding of pathogenesis and pathophysiology of IEMs, by validating diagnostic biomarkers, discovering new specific metabolic patterns and new IEMs itself. The expansion of Metabolomics in clinical biochemistry and laboratory medicine has brought these approaches in clinical practice as part of newborn screenings, as an exam for differential diagnosis between IEMs, and evaluation of metabolites in follow up as markers of severity or therapies efficacy. Lastly, several research groups are trying to profile metabolomics data in platforms to have a holistic vision of the metabolic, proteomic and genomic pathways of every single patient. In 2018 this team has made a review of literature to understand the value of Metabolomics in IEMs. Our review offers an update on use and perspectives of metabolomics in IEMs, with an overview of the studies available from 2018 to 2022

Detection of Polyethylene Glycol Thyrotropin (TSH) Precipitable Percentage (Macro-TSH) in Patients with a History of Thyroid Cancer

Background: Owing to its large molecular size, polyethylene glycol (PEG)-precipitable thyrotropin (TSH) can accumulate in the circulation, elevating TSH levels. PEG-precipitable TSH can be used to detect macro-TSH (mTSH) in serum. Our aim was to evaluate the prevalence of mTSH in patients who had undergone thyroidectomy for thyroid cancer.Methods: Seventy-three thyroid cancer patients and 24 control subjects on levothyroxine (LT4) TSH-suppressive or replacement therapy were evaluated. Screening for mTSH was performed by adding PEG to serum in order to precipitate.-globulin. A percentage of PEG-precipitable TSH >= 80% was considered suggestive of mTSH.Results: No correlation between free-T4 (fT4) and TSH levels was found. PEG-precipitable TSH was 39.3%+/- 1.9% in thyroid cancer patients and 44.1%+/- 3.9% in controls. Macro-TSH was deemed to be present in one thyroid cancer patient and in two control subjects. Only in the thyroid cancer group was PEG-precipitable TSH found to be negatively correlated with fT4 concentration. No correlation was found between PEG-precipitable TSH and other clinical conditions in any patients.Conclusion: The presence of mTSH seems to be a rare phenomenon in thyroid cancer. In some patients with low PEG-precipitable TSH, a reduction in LT4 dosage could be suggested. LT4 dosage adjusted to body weight is the main factor in maintaining TSH in a semi-suppressed or normal range. Evaluation of mTSH could be necessary in patients in whom a balance is required between adequate TSH suppression and the avoidance of unnecessary exogenous hyperthyroxinemia

Is Serum Cystatin C a Sensitive Marker of Glomerular Filtration Rate (GFR)? A Preliminary Study on Renal Transplant Patients

Human cystatin C is a basic low molecular mass protein (13,359 Dalton) freely filtered through the glomerulus and almost completely re-absorbed and catabolized by proximal tubular cells. We measured serum cystatin C in 38 kidney transplant patients (23 males, 15 females) aged between 6 and 32 years. To assess renal function, serum and urinary creatinine were also determined in all patients, and creatinine clearance was finally calculated. Cystatin C was determined by a particle-enhanced turbidimetric assay, and creatinine was measured by gas chromatography-mass spectrometry. To compare the diagnostic efficiency of cystatin C with that of creatinine, inulin clearance was performed on 12 renal transplant patients, and receiver operating characteristic (ROC) analysis was applied. The results of this study demonstrate that serum cystatin C significantly increases in renal transplant patients with reduced creatinine clearance (70 mL/min per 1.73 m2) and that the diagnostic accuracy of serum cystatin C is better than of serum creatinine. Cystatin C may be utilized as a very marker of reduced GFR

Metabolic and cardiovascular risk in patients with a history of differentiated thyroid carcinoma: A case-controlled cohort study

Hyperthyroidism seems to increase metabolic and cardiovascular risk, while the effects of sub-clinical hyperthyroidism are controversial. We evaluated metabolic and cardiovascular parameters in differentiated thyroid carcinoma (DTC) patients with suppressed thyrotropin (TSH) due to levo-thyroxine (L-T4) therapy. We studied DTC patients and, as a control group, patients with a history of surgery for non-malignant thyroid pathology. Significantly higher insulin and lower HDL-cholesterol levels were recorded in DTC subjects. In both groups, insulin levels were significantly related with body mass index (BMI) but not with age or L-T4 dosage. In DTC patients, a significant negative correlation was seen between HDL-cholesterol and BMI or L-T4 dosage. In both groups, intima-media thickness (IMT) correlated positively with age, BMI, glucose levels and systolic blood pressure. In DTC patients, increased IMT was significantly correlated with glycated hemoglobin (HbA1c), cholesterol and triglycerides. In DTC patients, C-reactive protein correlated positively with insulin, insulin resistance, triglycerides and systolic blood pressure, and negatively with HDL-cholesterol. In both DTC and control subjects, fibrinogen correlated positively with age, BMI, increased IMT, HbA1c and systolic blood pressure. In DTC subjects, plasma fibrinogen concentrations correlated positively with insulin resistance, cholesterol and LDL-cholesterol, and negatively with TSH levels. Our data confirm that the favorable evolution of DTC can be impaired by a high incidence of abnormal metabolic and cardiovascular data that are, at least in part, related to L-T4 therapy. These findings underline the need for adequate L-T4 titration

Metabolomics in Otorhinolaryngology

Otorhinolaryngology (Ear, Nose and Throat-ENT) focuses on inflammatory, immunological, infectious, and neoplastic disorders of the head and neck and on their medical and surgical therapy. The fields of interest of this discipline are the ear, the nose and its paranasal sinuses, the oral cavity, the pharynx, the larynx, and the neck. Besides surgery, there are many other diagnostic aspects of ENT such as audiology and Vestibology, laryngology, phoniatrics, and rhinology. A new advanced technology, named metabolomics, is significantly impacting the field of ENT. All the “omics” sciences, such as genomics, transcriptomics, and proteomics, converge at the level of metabolomics, which is considered the integration of all “omics.” Its application will change the way several of ENT disorders are diagnosed and treated. This review highlights the power of metabolomics, including its pitfalls and promise, and several of its most relevant applications in ENT to provide a basic understanding of the metabolites associated with these districts. In particular, the attention has been focused on different heterogeneous diseases, from head and neck cancer to allergic rhinitis, hearing loss, obstructive sleep apnea, noise trauma, sinusitis, and Meniere’s disease. In conclusion, metabolomics study indicates a “fil rouge” that links these pathologies to improve three aspects of patient care: diagnostics, prognostics, and therapeutics, which in one word is defined as precision medicine