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Customer requests are addressed to safe products that best express their characteristics of "naturalness" and "freshness" for their entire shelf life; therefore, scientific research has been exploring the use of "non-thermal technologies". Thermosonication using low-frequency focused ultrasound determines bacterial inactivation through the phenomenon of "cavitation", guaranteeing high-quality standards of safety, nutrition, and freshness of the products. The present work aims to evaluate the effectiveness of the inactivation of Salmonella typhimurium in culture broth by low-frequency focused thermosonication with two different operational parameters: sublethal temperature (40°C, 50°C) and treatment time (5, 10, and 15 minutes). Treatment determined a bacterial load reduction compared to the negative control (untreated inoculum), which was statistically significant at the t-test (p<0.05). Average decreases of 1.5 log and 3.5 CFU/mL were observed, respectively, after treatment and after 24 hours of storage at +4°C. Treatment at 50°C for 15 minutes was the most effective (average value: 3.06 log CFU/mL; minimum value: 2.13 log CFU/mL; maximum value: 4.59 log CFU/mL). However, strains have shown markable variability: one of them even showed an increase in the microbial load 24 hours after treatment at 40°C for 5 minutes (-0.20 log CFU/mL); however, the same treatment showed a reduction of bacterial charge in all the other strains (average value: 1.05 log CFU/mL; minimum value: -0.20 log CFU/mL; maximum value: 2.28 log CFU/mL). This study poses numerous perspectives on the use of low-frequency focused thermosonication treatment in the food industry as a sustainable and safe alternative to classic thermal treatments. [ABSTRACT FROM AUTHOR]

The enzyme UDP-glucose: glycoprotein glucosyltransferase (UGGT) is the gatekeeper of protein folding within the endoplasmic reticulum (ER). One-third of the human proteome traverses the ER where folding and maturation are facilitated by a complex protein homeostasis network. Both glycan modifications and disulfide bonds are of key importance in the maturation of these ER proteins. The actions of UGGT are intimately linked to the glycan code for folding and maturation of secretory proteins in the ER. UGGT selectively glucosylates the N-linked glycan of misfolded proteins so that they can reenter the lectin-folding chaperone cycle and be retained within the ER for further attempts at folding. An intriguing aspect of UGGT function is its interaction with its poorly understood cochaperone, the 15 kDa selenoprotein known as SELENOF or SEP15. This small protein contains a rare selenocysteine residue proposed to act as an oxidoreductase toward UGGT substrates. AlphaFold2 predictions of the UGGT1/SEP15 complex provide insight into this complex at a structural level. The predicted UGGT1/SEP15 interaction interface was validated by mutagenesis and coimmunoprecipitation experiments. These results serve as a springboard for models of the integrated action of UGGT1 and SEP15. [ABSTRACT FROM AUTHOR]

Aims: To collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM. Methods: Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case–control) studies and randomized clinical trials performed on humans up to June 1st, 2023. Results: We retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45–0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes. Conclusions: People with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes. [ABSTRACT FROM AUTHOR]

This qualitative diary study explored emotional responses of college students to social distancing (SD) protocols during the COVID-19 pandemic. Twenty college students in an undergraduate senior capstone psychology course at a medium-sized public university in the Eastern USA wrote reflective diaries for several weeks. Their reactions to ongoing SD protocols were analyzed across four cohorts, from the virus onset in spring 2020 through late 2021. Entries related to SD protocols were selected, then coded with etic and emic coding strategies to characterize the aspects of SD and associated emotions. Participants discussed ten aspects of SD in passages that were complex in emotion, most strongly fear, joy, and sadness, and to a lesser extent, anger, disgust, and surprise. Gender differences in emotional reactions were minimal. Results are discussed in relation to student well-being, the socio-emotional toll of SD protocols, and ways to ease negative SD impacts. [ABSTRACT FROM AUTHOR]

In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 106 PBSC/kg, 2.6% (n = 7) mobilized < 4 × 106 PBSC/kg and 7.7% (n = 21) failed the collection. Similar results were obtained for the planned second leukapheresis, with only one patient failing both attempts. Median count of reinfused PBSC was 5 × 106/kg and median time to recovery from neutropenia G4 was 10 days from ASCT. No impact of mobilizing subtype or number of reinfused PBSC on hematological recovery and LEN dose reduction was noted. At a median follow-up of 75 months from ASCT, PFS and OS of transplanted patients were 50% and 73%, respectively. A long lasting G4 neutropenia after ASCT (> 10 days) was associated with a worse outcome, both in terms of PFS and OS. In conclusion, although the harvesting procedures proved feasible for younger MCL patients, long-lasting cytopenia following ASCT remains a significant issue: this can hinder the administration of effective maintenance therapies, potentially increasing the relapse rate and negatively affecting survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Relapse and refractory (R/R) rates after first‐line R‐CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. Aims: We conducted a retrospective real‐world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. Material and Methods: Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. Results: At a median follow up of 50 months, 5‐year overall survival from diagnosis (OS‐1) was 66.5%, and 2‐year progression free survival (PFS‐1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R‐CHOP. Most employed salvage treatments included platinum salt‐based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS‐2 and PFS‐2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS‐2 or PFS‐2 in patients treated with platinum‐based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of <2 sites were associated with better OS‐2. Discussion: Our findings confirm very poor outcomes of R/R DLBCL in the rituximab era. Widespread approval by national Medicine Agencies of novel treatments such as CAR‐T cells and bispecific antibodies as second‐line is eagerly awaited to improve these outcomes. [ABSTRACT FROM AUTHOR]

Background: ChatGPT is an open-source natural language processing software that replies to users' queries. We conducted a cross-sectional study to assess people living with Multiple Sclerosis' (PwMS) preferences, satisfaction, and empathy toward two alternate responses to four frequently-asked questions, one authored by a group of neurologists, the other by ChatGPT. Methods: An online form was sent through digital communication platforms. PwMS were blind to the author of each response and were asked to express their preference for each alternate response to the four questions. The overall satisfaction was assessed using a Likert scale (1–5); the Consultation and Relational Empathy scale was employed to assess perceived empathy. Results: We included 1133 PwMS (age, 45.26 ± 11.50 years; females, 68.49%). ChatGPT's responses showed significantly higher empathy scores (Coeff = 1.38; 95% CI = 0.65, 2.11; p > z < 0.01), when compared with neurologists' responses. No association was found between ChatGPT' responses and mean satisfaction (Coeff = 0.03; 95% CI = − 0.01, 0.07; p = 0.157). College graduate, when compared with high school education responder, had significantly lower likelihood to prefer ChatGPT response (IRR = 0.87; 95% CI = 0.79, 0.95; p < 0.01). Conclusions: ChatGPT-authored responses provided higher empathy than neurologists. Although AI holds potential, physicians should prepare to interact with increasingly digitized patients and guide them on responsible AI use. Future development should consider tailoring AIs' responses to individual characteristics. Within the progressive digitalization of the population, ChatGPT could emerge as a helpful support in healthcare management rather than an alternative. [ABSTRACT FROM AUTHOR]

Elevated plasma concentration of cholesterol bound to LDL (LDL-C) is the predominant risk factor for cardiovascular (CV) diseases. An important number of clinical trials demonstrated that the use of statins to reduce LDL-C is beneficial in terms of prevention of CV events in the entire population. Over time, specific LDL-C targets to be achieved have been established to guarantee the best outcome for the patient from the therapeutic intervention. The fundamental role of the clinical laboratory in diagnosis and treatment monitoring of dyslipidemias, requires that harmonization in the different phases of the laboratory process be pursued and achieved in order to allow the correct management of patients. The harmonization process has been the subject of national and international recommendations over time; however, a further recommendation is essential, considering that some recent evidences testify to a sub-optimal adoption of the indications by a non-negligible number of laboratories, confirming the need to repeat training and information activities. Aim of this joint document is to analyze the importance of the therapeutic targets to be achieved and the critical elements of laboratory diagnostic related to dyslipidemia, in order to provide indications for the harmonization of the reporting of the lipid profile. According to these recommendations, the lipid parameters should be reported accompanied by the therapeutic goals differentiated by the risk categories for LDL-C and non-HDL-C and by the threshold values for the other parameters. The use of comparison terms like Reference values or Normal values in the laboratory report must be definitely abandoned. [ABSTRACT FROM AUTHOR]

Background: the poor adherence to guidelines approved by scientific societies are widely described as a possible cause of criticisms in the management of several diseases. In the setting of dyslipidemia, a lack of compliance with clinical and biochemical recommendations defining the informations that should be included in the laboratory report, could be a relevant issue. Methods: in order to verify the state-of-the art of this specific topic, a survey containing 8 questions spanning from the pre-analitycal phase (panel of tests, nonfasting testing), to analytical (types of methods and equations) and to post-analytical phase (reference interval, desirable values, therapeutic goals) was sent to the laboratory professionals registered in the Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC). Results: the most interesting results demonstrate that: about 40% of the laboratories add to the traditional lipid panels (total, LDL and HDL cholesterol, tryglicerides) the recommended measurement of apolipoproteins (Apo-A1, Apo-B and Lpa); 89% adopt the fasting testing; 73.6% use direct methods to measure HDL-C and 29% calculate LDL-C using Friedewald equation; 87.3% of the values are reported using the traditional (mg/dL) units; 64.5% use the reference interval as comparator, inadequate for the most part of lipid tests, 51.4% desirable levels, only 5.61% the recommended therapeutic goals. Discussion: on the basis of the obtained data, a shared improvement in the adoption and application of the recommendations published by SIBioC but poorly adopted until now, seems to be a fundamental activity that should be undertaken in the near future. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disease. Neuropathic pain (NP), related to peripheral inflammation, is among its earliest manifestations. This preliminary open-label investigation aimed to evaluate the efficacy of ultramicronized Palmitoylethanolamide (umPEA) in the management of NP. Methods: A total of 14 patients with CIDP, already undergoing immunoglobulin (Ig) therapy, were divided into two groups: Group A received umPEA 600 mg twice daily in addition to Ig for 60 days, followed by Ig alone until the end of the observation (180 days); Group B received Ig alone for 120 days and subsequently umPEA + Ig in the last 60 days of the study. Painful symptom intensity and quality of life were assessed by the Numeric Rating Scale, Neuropathic Pain Symptoms Inventory, and Five Dimensions Health Questionnaire. The safety umPEA profile was evaluated. Results: UmPEA in addition to immunoglobulins allowed for a significant improvement over time in all NP symptoms intensity (p = 0.0007) and in patients' quality of life (p = 0.0036). Conclusions: This study suggests umPEA as a safe and effective treatment in addition to immunoglobulins to improve NP, ameliorating the patient's health status. These results highlight the importance of neuroinflammation modulation in the management of CIDP's painful symptoms, drawing attention to umPEA's potential use also in neuropathies of different etiologies. [ABSTRACT FROM AUTHOR]

The Indoor Environmental Quality (IEQ) combines thermal, visual, acoustic, and air-quality conditions in indoor environments and affects occupants' health, well-being, and comfort. Performing continuous monitoring to assess IEQ is increasingly proving to be important, also due to the large amount of time that people spend in closed spaces. In the present study, the design, development, and metrological characterization of a low-cost multi-sensor device is presented. The device is part of a wider system, hereafter referred to as PROMET&O (PROactive Monitoring for indoor EnvironmenTal quality & cOmfort), that also includes a questionnaire for the collection of occupants' feedback on comfort perception and a dashboard to show end users all monitored data. The PROMET&O multi-sensor monitors the quality conditions of indoor environments thanks to a set of low-cost sensors that measure air temperature, relative humidity, illuminance, sound pressure level, carbon monoxide, carbon dioxide, nitrogen dioxide, particulate matter, volatile organic compounds, and formaldehyde. The device architecture is described, and the design criteria related to measurement requirements are highlighted. Particular attention is paid to the calibration of the device to ensure the metrological traceability of the measurements. Calibration procedures, based on the comparison to reference standards and following commonly employed or ad hoc developed technical procedures, were defined and applied to the bare sensors of air temperature and relative humidity, carbon dioxide, illuminance, sound pressure level, particulate matter, and formaldehyde. The next calibration phase in the laboratory will be aimed at analyzing the mutual influences of the assembled multi-sensor hardware components and refining the calibration functions. [ABSTRACT FROM AUTHOR]

Background: The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD). Aim: To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD. Methods: A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient. Results: In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD. Conclusion: In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD. [ABSTRACT FROM AUTHOR]

The Mediterranean Diet (MD) is described in the literature as a beneficial dietary pattern for neurodegenerative diseases such as Multiple Sclerosis (MS). The objective of this study was to evaluate the dietary habits in people with MS (pwMS) and to test whether adherence to the MD could have an impact on the severity of the disease measured as the MS severity score (MSSS). Adherence to the MD was assessed in 31 PwMS using the Mediterranean Diet Adherence Screener (MEDAS), the Pyramid-based Mediterranean Diet Score (PyrMDS) index, and the Italian Mediterranean Index (IMI), and their eating habits were recorded in a food diary for a one-year follow-up. When data obtained from dietary analysis were compared to the MSSS, results showed that pwMS with lower MSSS adhere more to the MD than the other pwMS groups according to the MEDAS index. Furthermore, a high consumption of fiber in the MS mild severity class was observed. Further studies are needed to clarify which of the nutritional components of the MD may impact the course of MS and if the sensitization of pwMS to MD adherence can be a strategy for mitigating the disease. [ABSTRACT FROM AUTHOR]

Despite the evidence demonstrating the clinical utility of cardiac specific biomarkers in improving cardiovascular risk evaluation in several clinical conditions, even the most recent reviews and guidelines fail to consider their measurement in order to enhance the accuracy of the evaluation of cardiovascular risk in pregnant women. The aim of this review article was to examine whether the assay of cardiac specific biomarkers can enhance cardiovascular risk evaluation in pregnant women, first by reviewing the relationships between the physiological state of pregnancy and cardiac specific biomarkers. The clinical relevance of brain natriuretic peptide (BNP)/NT-proBNP and high-sensitivity cardiac troponin I/high-sensitivity cardiac troponin T (hs-cTnI/hs-cTnT) assay in improving cardiovascular risk evaluation is examined based on the results of clinical studies on subjects with normal and those with complicated pregnancy. Finally, the analytical approaches and clinical objectives related to cardio specific biomarkers are advocated in order to allow an early and more accurate evaluation of cardiovascular risk in pregnant women. [ABSTRACT FROM AUTHOR]

This article discusses a recent study that evaluated a new method for measuring high-sensitivity cardiac troponin I (hs-cTnI) levels in comparison to an established assay. The study found that the new method had high precision, sensitivity, and specificity, and its diagnostic performance was comparable to the established assay. The use of hs-cTnI methods has allowed for faster diagnosis of non-ST-elevation myocardial infarction (NSTEMI), reducing the time to diagnosis from 6-12 hours to less than 3 hours. However, the article also highlights the importance of accurately evaluating the limit of blank values for hs-cTnI assays and discusses potential interferences that can affect the measurement of hs-cTnI and potentially lead to false diagnoses. The authors conclude that further studies using standardized protocols are needed to confirm the accuracy of the new method. [Extracted from the article]

A study published in Clinical Chemistry & Laboratory Medicine compared a new chemiluminescent method for measuring high-sensitivity cardiac troponin I (hs-cTnI) levels to the established ARCHITECT hs-cTnI method. The new method was found to be precise, sensitive, and specific, with diagnostic performance similar to the ARCHITECT method. The use of hs-cTnI and hs-cTnT methods has allowed for faster diagnosis of non-ST-elevation myocardial infarction (NSTEMI), reducing diagnosis time from 6-12 hours to less than 3 hours. The study suggests that the new CLIA hs-cTnI method is a reliable alternative for accurately diagnosing myocardial infarction, but further studies are needed to confirm its accuracy. The article also discusses the importance of evaluating the limit of blank values for hs-cTnI assays and the potential interference of substances that can lead to false diagnoses of myocardial injury. [Extracted from the article]

Background: COVID-19 vaccines have been recommended to people with multiple sclerosis (pwMS) and, to ensure durable immunity, a third booster dose has been administered in several countries. Data about potential risks associated with the third booster dose in pwMS, such as vaccine-triggered disease exacerbations, are still scarce. Objective: To investigate whether the administration of a third booster dose of mRNA COVID-19 vaccines was associated with an increased risk of short-term disease reactivation in a large cohort of pwMS. Methods: We retrospectively selected 1265 pwMS who received a third booster dose of an mRNA COVID-19 vaccine. Demographic and clinical data were collected, including the presence, number and characteristics of relapses in the 60 days prior to and after the third booster dose. Results: In the selected cohort, the relapse rate in the two months after administration of the third booster dose of mRNA COVID-19 vaccines did not increase when compared with the prior two months. Indeed, the percentage of pwMS experiencing relapses in the 60 days following the administration of the third booster dose was 2.1%, similar to the percentage recorded in 60 days prior to vaccination, which was 1.9%. Conclusions: The third booster dose of mRNA COVID-19 vaccines appeared to be safe for pwMS. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the impressive efficacy of chimeric antigen receptor-T (CAR-T) cell therapy in the treatment of some subtypes of lymphomas, many patients are either not eligible or relapse after treatment. Thus, great efforts are being made to further improve the depth and durability of clinical responses, as well as to expand the settings in which CAR-T cells can be employed. The present review aims to summarize those efforts, offering an overview of recent advances and future perspectives in the field. In the last decade, anti-CD19 CAR-T cell therapy has led to a treatment paradigm shift for B-cell non-Hodgkin lymphomas, first with the approval for relapsed/refractory (R/R) large B-cell lymphomas and subsequently for R/R mantle cell and follicular lymphoma. Many efforts are continuously being made to extend the therapeutic setting in the lymphoma field. Several reports are supporting the safety and efficacy of CAR-T cells in patients with central nervous system disease involvement. Anti-CD30 CAR-T cells for the treatment of Hodgkin lymphoma are in development and early studies looking for the optimal target for T-cell malignancies are ongoing. Anti-CD19/CD20 and CD19/CD22 dual targeting CAR-T cells are under investigation in order to increase anti-lymphoma activity and overcome tumor immune escape. Allogeneic CAR product engineering is on the way, representing a rapidly accessible 'off-the-shelf' and potentially more fit product. In the present manuscript, we will focus on recent advances in CAR-T cell therapy for lymphomas, including new settings and future perspectives in the field, reviewing data reported in literature in the last decade up to October 2023. [ABSTRACT FROM AUTHOR]

The therapeutic administration of subcutaneous immunoglobulin (SCIg) offers various advantages over intravenous immunoglobulin (IVIg). This narrative review examines and compares SCIg versus IVIg in chronic inflammatory demyelinating polyneuropathy (CIDP). SCIg is as effective as IVIg but is better tolerated and easier to administer, as intravenous access is not required. Furthermore, SCIg administration is more convenient and cost-effective than IVIg, enabling flexible treatment scheduling at home and improving patients' overall quality of life. The availability of highly concentrated immunoglobulin G (IgG) subcutaneous solutions, such as IgPro20, a 20% IgG solution stabilized with L-proline, allows for the administration of larger volumes in a single session, while the parallel development of new technological devices enables the delivery of higher doses over a shorter time. Based on the results of the PATH study, SCIg has become a well-established therapy in CIDP. In addition to discussing the advantages of SCIg, this review summarizes the evolution of SCIg by discussing all the relevant clinical studies which have considered its use in the treatment of CIDP. [ABSTRACT FROM AUTHOR]

The aim of this article review is to analyze some models and clinical issues related to the implementation of accelerated diagnostic protocols based on specific cardiac biomarkers in patients admitted to the emergency department (ED) with symptoms compatible with acute cardiac disorders. Four specific clinical issues will be discussed in detail: (a) pathophysiological and clinical interpretations of circulating hs-cTnI and hs-cTnT levels; (b) the clinical relevance and estimation of the biological variation of biomarkers in patients admitted to the ED with acute and severe diseases; (c) the role and advantages of the point-of-care testing (POCT) methods for cardiac-specific biomarkers in pre-hospital and hospital clinical practice; and (d) the clinical role of specific cardiac biomarkers in patients with acute heart failure (AHF). In order to balance the risk between a hasty discharge versus the potential harms caused by a cardiac assessment in patients admitted to the ED with suspected acute cardiovascular disease, the measurement of specific cardiac biomarkers is essential for the early identification of the presence of myocardial dysfunction and/or injury and to significantly reduce the length and costs of hospitalization. Moreover, specific cardiac biomarkers (especially hs-cTnI and hs-cTnT) are useful predictors of mortality and major adverse cardiovascular events (MACE) in patients admitted to the ED with suspected acute cardiovascular disease. To guide the implementation of the most rapid algorithms for the diagnosis of Non-ST-Elevation Myocardial Infarction (NSTEMI) into routine clinical practice, clinical scientific societies and laboratory medicine societies should promote collaborative studies specifically designed for the evaluation of the analytical performance and, especially, the cost/benefit ratio resulting from the use of these clinical protocols and POCT methods in the ED clinical practice. [ABSTRACT FROM AUTHOR]

Aim: The risk for Herpes zoster (HZ) and its complications is higher in people with diabetes mellitus (DM). Our aim is to assess efficacy and effectiveness of the currently available live-attenuated zoster vaccine (LZV) and recombinant zoster vaccine (RZV) in adults with DM. Methods: A Systematic Review and Meta-analysis of clinical trials and observational studies comparing incidence of HZ and its complications in vaccinated and unvaccinated people with DM was performed, on PubMed, Cochrane, Clinical Trials.gov and Embase databases, up to January 15th, 2023. Risk of bias was assessed through the Cochrane Collaboration tool and the Newcastle–Ottawa Scale. The protocol was registered on the PROSPERO website (CRD42022370705). Results: Only three observational studies reported LZV efficacy and effectiveness in people with DM. A lower risk for HZ infection (MH-OH Ratio 95% CI = 0.52 [0.49, 0.56] was observed, for unadjusted analysis, and 0.51 [0.46, 0.56] for adjusted analysis, both with P < 0.00001 and no heterogeneity). No data on LZV safety were reported. A pooled analysis of two trials comparing RZV and placebo, showed a reduced risk for HZ incidence: (95% CI Odds Ratio: 0.09 [0.04–0.19]), with no difference in severe adverse events and mortality. Conclusions: In our meta-analysis of three observational studies LZV showed a 48% effectiveness in reducing HZ incidence in adults with diabetes whereas in a pooled analysis of two RCTs, RZV showed a 91% efficacy. No data are available on the effects of vaccination on the incidence and severity of HZ-related complications among subjects with diabetes. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 69-year-old Caucasian woman who presented with an uncommon presentation of caecum cancer. The patient had a history of severe chronic constipation and faecal incontinence and had previously undergone an ileal neoappendicostomy for colonic irrigation. Colonoscopy and CT revealed a partially obstructing tumor in the caecum, and the patient underwent right colectomy. The post-operative period was uneventful, and the final histopathology report confirmed locally advanced cancer. The article also mentions the importance of establishing a strict screening program for patients undergoing surgery for chronic constipation. [Extracted from the article]

Many studies have demonstrated the crucial pathophysiological and clinical relevance to evaluate cardiac specific biomarkers (natriuretic peptides and cardiac troponins) for the diagnosis and risk prediction of cardiovascular diseases in the general population and in patients with cardiovascular diseases as well. However, some important pathophysiological aspects still need to be better clarified, such as the possible influence of the sex hormones on the circulating concentrations of cardiac biomarkers and therefore on the interpretation of changes in their circulating levels in healthy subjects and in patients with cardiovascular disease. The primary purpose of this document is to discuss the pathophysiological and clinical relevance of sex- and/or gender-related differences in circulating levels of cardiac biomarkers. In the first part of this document, the pathophysiological mechanisms related to age, sex, gonadal development and function (including pregnancy) will be discussed. In the second part, the pharmacological effects of sex hormone therapy will be discussed. Sex hormones can be prescribed to patients of both sexes as replacement therapy, for prevention or treatment. However, many transgender persons undergo treatment with gender-affirming hormone therapy in order to help aligning their physical traits and gender identity. Accordingly, the possible effect of sex steroid hormone administration on the circulating levels of cardiac-specific biomarkers will be discussed. The most recent studies confirm the pathophysiological hypothesis that the androgenic steroid hormones (particularly testosterone) are generally associated with higher levels of cardiac troponins. On the other hand, the administration of estrogenic steroid hormones (particularly estradiol) can stimulate the production and release of cardiac natriuretic hormones from cardiomyocytes. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to discuss in detail the analytical features and clinical relevance of the high-sensitivity cardiac troponin I (hs-cTnI) POCT methods in patients suspected of having NSTEMI, especially taking into consideration the possible application of the recommendations reported by the international guidelines in the clinical practice. In the first part, we will describe the analytical performance and clinical results of the new POCT methods for the measurement of hs-cTnI, in comparison with those of hs-cTnI methods used in clinical laboratories with the most common automated analytical platforms, and those of non high-sensitivity POCT. In the second part, we will discuss the 2023 recommendations of the IFCC Committee on the Clinical Application of Cardiac Biomarkers (IFCC C-CB) document, with the aim to provide some useful recommendations on educational paths to implement the use of POCT hs-cTnI methods in clinical practice. In the last part, we will describe some possible technological developments of POCT hs-cTnI methods, with the goal to bring these tests even "closer" to the patient and/or to continuously monitor the circulating biomarker levels. [ABSTRACT FROM AUTHOR]

Patients with chronic coronary syndrome (CCS) represent a heterogeneous group for their risk profiles, clinical manifestations as well as presence of obstructive coronary atherosclerosis, inducible ischemia, and myocardial damage.[1] Cardiac troponins are structural proteins found in the myofibrils of cardiomyocytes and, because of their cardiac specificity, determination of their circulating levels is the keystone for the diagnosis of myocardial injury in patients with suspected acute coronary syndromes.[2] Development of high sensitivity assays has enhanced the ability to detect low circulating levels of cardiac troponin I and T (hs-cTnI and hs-cTnT).[[3]] Elevated hs-cTnT and hs-cTnI plasma concentrations have been associated with adverse cardiovascular outcome in the general population[[5]] and in patients with coronary artery disease (CAD).[[7], [9], [11]] However, in patients with CCS, it is not fully clear whether they are associated with specific risk profiles and disease manifestations, including obstructive CAD and inducible myocardial ischemia, potentially causing chronic myocardial injury. In the whole population, obstructive CAD was documented at coronary CTA in 107 patients (29%), inducible ischemia at non-invasive stress imaging in 100 patients (27%). Patients with obstructive CAD, showed significantly higher levels of hs-cTnT than patients without obstructive CAD, independently from the presence of ischemia. Patients with inducible ischemia had significantly higher levels of hs-cTnI as compared with patients without ischemia, independently from the presence of obstructive CAD (Figure 1A). [Extracted from the article]

Background and purpose: Although two doses of COVID‐19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease‐modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Results: Four hundred seventy‐three pwMS were analyzed. Compared to untreated patients, there was a 50‐fold decrease (95% confidence interval [CI] = 14.3–100.0, p < 0.001) in serum SARS‐CoV‐2 antibody levels in those on rituximab, a 20‐fold decrease (95% CI = 8.3–50.0, p < 0.001) in those on ocrelizumab, and a 2.3‐fold decrease (95% CI = 1.2–4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti‐CD20 drugs rituximab and ocrelizumab showed a 2.3‐fold lower gain (95% CI = 1.4–3.8, p = 0.001), whereas those on fingolimod showed a 1.7‐fold higher gain (95% CI = 1.1–2.7, p = 0.012), compared to patients treated with other DMTs. Conclusions: All pwMS increased their serum SARS‐CoV‐2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff. [ABSTRACT FROM AUTHOR]

Background: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. Objective: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. Methods: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). Results: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. Conclusion: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy. [ABSTRACT FROM AUTHOR]

Background and objectives: Long lasting immune response to anti-SARS-CoV-2 vaccination in people with Multiple Sclerosis (pwMS) is still largely unexplored. Our study aimed at evaluating the persistence of the elicited amount of neutralizing antibodies (Ab), their activity and T cell response after three doses of anti-SARS-CoV-2 vaccine in pwMS. Methods: We performed a prospective observational study in pwMS undergoing SARS-CoV-2 mRNA vaccinations. Anti-Region Binding Domain (anti-RBD) of the spike (S) protein immunoglobulin G (IgG) titers were measured by ELISA. The neutralization efficacy of collected sera was measured by SARS-CoV-2 pseudovirion-based neutralization assay. The frequency of Spike-specific IFNγ-producing CD4+ and CD8+ T cells was measured by stimulating Peripheral Blood Mononuclear Cells (PBMCs) with a pool of peptides covering the complete protein coding sequence of the SARS-CoV-2 S. Results: Blood samples from 70 pwMS (11 untreated pwMS, 11 under dimethyl fumarate, 9 under interferon-g, 6 under alemtuzumab, 8 under cladribine, 12 under fingolimod and 13 under ocrelizumab) and 24 healthy donors were collected before and up to six months after three vaccine doses. Overall, anti-SARS-CoV-2 mRNA vaccine elicited comparable levels of anti-RBD IgGs, neutralizing activity and anti-S T cell response both in untreated, treated pwMS and HD that last six months after vaccination. An exception was represented by ocrelizumab-treated pwMS that showed reduced levels of IgGs (p<0.0001) and a neutralizing activity under the limit of detection (p<0.001) compared to untreated pwMS. Considering the occurrence of a SARS-CoV-2 infection after vaccination, the Ab neutralizing efficacy (p=0.04), as well as CD4+ (p=0.016) and CD8+ (p=0.04) S-specific T cells, increased in treated COVID+ pwMS compared to uninfected treated pwMS at 6 months after vaccination. Discussion: Our follow-up provides a detailed evaluation of Ab, especially in terms of neutralizing activity, and T cell responses after anti-SARS-CoV-2 vaccination in MS context, over time, considering a wide number of therapies, and eventually breakthrough infection. Altogether, our observations highlight the vaccine response data to current protocols in pwMS and underline the necessity to carefully follow-up anti-CD20-treated patients for higher risk of breakthrough infections. Our study may provide useful information to refine future vaccination strategies in pwMS. [ABSTRACT FROM AUTHOR]

This article discusses a case of caecum cancer in a 69-year-old woman who had previously undergone an ileal neoappendectomy for severe chronic constipation and fecal incontinence. The patient presented with an inability to self-catheterize and further examination revealed a partially obstructing tumor in the caecum. The patient underwent right colectomy with terminal ileostomy and distal mucous fistula, and the final histopathology report confirmed locally advanced cancer. The article highlights the importance of establishing a screening program for patients who have undergone surgery for chronic constipation, as they may be at an increased risk of cancer. [Extracted from the article]

Multiple sclerosis (MS) primarily affects adult females. However, in the last decades, rising incidence and prevalence have been observed for demographic extremes, such as pediatric-onset MS (POMS; occurring before 18 years of age) and late-onset MS (corresponding to an onset above 50 years). These categories show peculiar clinical-pathogenetic characteristics, aging processes and disease courses, therapeutic options, and unmet needs. Nonetheless, several open questions are still pending. POMS patients display an important contribution of multiple genetic and environmental factors such as EBV, while in LOMS, hormonal changes and pollution may represent disease triggers. In both categories, immunosenescence emerges as a pathogenic driver of the disease, particularly for LOMS. In both populations, patient and caregiver engagement are essential from the diagnosis communication to early treatment of disease-modifying therapy (DMTs), which in the elderly population appears more complex and less proven in terms of efficacy and safety. Digital technologies (e.g., exergames and e-training) have recently emerged with promising results, particularly in treating and following motor and cognitive deficits. However, this offer seems more feasible for POMS, being LOMS less familiar with digital technology. In this narrative review, we discuss how the aging process influences the pathogenesis, disease course, and therapeutic options of both POMS and LOMS. Finally, we evaluate the impact of new digital communication tools, which greatly interest the current and future management of POMS and LOMS patients. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a multifactorial neurological disease characterized by chronic inflammation and immune-driven demyelination of the central nervous system (CNS). The rising number of MS cases in the last decade could be partially attributed to environmental changes, among which the alteration of the gut microbiome driven by novel dietary habits is now of particular interest. The intent of this review is to describe how diet can impact the development and course of MS by feeding the gut microbiome. We discuss the role of nutrition and the gut microbiota in MS disease, describing preclinical studies on experimental autoimmune encephalomyelitis (EAE) and clinical studies on dietary interventions in MS, with particular attention to gut metabolites-immune system interactions. Possible tools that target the gut microbiome in MS, such as the use of probiotics, prebiotics and postbiotics, are analyzed as well. Finally, we discuss the open questions and the prospects of these microbiome-targeted therapies for people with MS and for future research. [ABSTRACT FROM AUTHOR]

The principal aim of this document is to provide a detailed documentation of the scientific activity carried out by the Italian Study Group on Cardiovascular biomarkers during these last three difficult years characterized by COVID-19 pandemic, that has put in strain the activity of all clinical laboratories (not only in Italy). Another important aim of this document is to discuss some important pathophysiological and clinical issues related to cardiac-specific biomarkers (i.e., cardiac natriuretic peptides and cardiac troponins), that still need not only further theoretical investigation, but also some multicenter clinical trials in order to evaluate and to improve their utilization in diagnosis, prognosis and managing of patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]

In accordance with all the most recent international guidelines, the variation of circulating levels of cardiac troponins I and T, measured with high-sensitivity methods (hs-cTnI and hs-cTnT), should be used for the detection of acute myocardial injury. Recent experimental and clinical evidences have demonstrated that the evaluation of hs-cTnI and hs-cTnT variations is particularly relevant: a) for the differential diagnosis of Acute Coronary Syndromes (ACS) in patients admitted to the Emergency Department (ED); b) for the evaluation of cardiovascular risk in patients undergoing major cardiac or non-cardiac surgery, and in asymptomatic subjects of the general population aged >55 years and with co-morbidities; c) for the evaluation of cardiotoxicity caused by administration of some chemotherapy drugs in patients with malignant tumors. The aim of this document is to discuss the fundamental statistical and biological considerations on the intraindividual variability of hs-cTnI and hs-cTnT over time in the same individual. Firstly, it will be discussed in detail as the variations of circulating levels strictly depend not only on the analytical error of the method used but also on the intra-individual variability of the biomarker. Afterwards, the pathophysiological interpretation and the clinical relevance of the determination of the variability of the hs-cTnI and hs-cTnT values ​​ in patients with specific clinical conditions are discussed. Finally, the evaluation over time of the variation in circulating levels of hs-cTnI and hs-cTnT is proposed for a more accurate estimation of cardiovascular risk in asymptomatic subjects from the general population. [ABSTRACT FROM AUTHOR]

The main aim of the present scoping review is to systematically review the available studies that investigated the associations between socioemotional alterations (i.e., social cognition impairments/alexithymia/difficulties in emotion regulation) and both reduced QoL and social functioning in patients with Multiple Sclerosis (MS). The articles were selected from the PubMed, PsycINFO, and Scopus databases. The main exclusion criteria were qualitative studies, articles that did not use validated instruments, and studies that did not investigate the association between socioemotional skills and QoL/social functioning in MS. Of the eight studies fulfilling the inclusion criteria, six found significant associations between social cognitive and emotion regulation abilities and QoL/social functioning in patients with MS, while two found no significant relationships particularly between the performance on social cognition tasks and QoL measures. Overall, the majority of findings seem to highlight that socioemotional alterations contribute to impaired QoL and social functioning in MS. However, given the still limited evidence, future studies are needed to replicate and confirm the available results, paying attention to two principal aspects: the use of standardized and ecological tasks for the assessment of social cognition skills and the recruitment of samples involving patients with different types of MS. [ABSTRACT FROM AUTHOR]

Despite being a common issue in people with multiple sclerosis (pwMS), sexual dysfunction is still underinvestigated. This work aims to assess the potential determinants of sexual dysfunction in pwMS by considering its relationship with disease severity (in terms of global disability), illness perception, and depressive symptoms. In this multicenter study, 1010 pwMS responded to an online survey. A serial mediation model considering negative illness perception and depressive symptoms as mediators of the relationship between disease severity and sexual dysfunction was conducted using the SPSS PROCESS Macro with bias-corrected bootstrapping (5000 samples). Disease severity exerts an indirect effect on sexual dysfunction via illness perception, both independently and through depressive symptoms. However, the results indicated that illness perception plays a more crucial role in sexual dysfunction in pwMS with mild disability than in pwMS with moderate-severe disability. This study suggests that higher disability increases its magnitude by enhancing negative illness perception, that, in turn, affects sexual dysfunction both directly and through depressive symptoms, especially in pwMS with mild disability. Modulating the effect of illness perception by favoring adaptive coping strategies might represent a valid approach to mitigate sexual dysfunction symptoms in MS. [ABSTRACT FROM AUTHOR]

Background: Monitoring antibody response following SARS-CoV-2 vaccination is strategic, and neutralizing antibodies represent the gold standard. The neutralizing response to Beta and Omicron VOCs was evaluated versus the gold standard by a new commercial automated assay. Methods: Serum samples from 100 healthcare workers from the Fondazione Policlinico Universitario Campus Biomedico and the Pescara Hospital were collected. IgG levels were determined by chemiluminescent immunoassay (Abbott Laboratories, Wiesbaden, Germany) and serum neutralization assay as the gold standard. Moreover, a new commercial immunoassay, the PETIA test Nab (SGM, Rome, Italy), was used for neutralization evaluation. Statistical analysis was performed with R software, version 3.6.0. Results: Anti-SARS-CoV-2 IgG titers decayed during the first ninety days after the vaccine second dose. The following booster dose significantly (p < 0.001) increased IgG levels. A correlation between IgG expression and neutralizing activity modulation was found with a significant increase after the second and the third booster dose (p < 0.05. Compared to the Beta variant of the virus, the Omicron VOC was associated with a significantly larger quantity of IgG antibodies needed to achieve the same degree of neutralization. The best Nab test cutoff for high neutralization titer (≥1:80) was set for both Beta and Omicron variants. Conclusion: This study correlates vaccine-induced IgG expression and neutralizing activity using a new PETIA assay, suggesting its usefulness for SARS-CoV2 infection management. [ABSTRACT FROM AUTHOR]

The cardiac troponins (cTns), cardiac troponin C (cTnC), cTnT, and cTnI are key elements of myocardial apparatus, fixed as protein complex on the thin filament of sarcomere and are involved in the regulation of excitation–contraction coupling of cardiomyocytes in the presence of Ca2+. Circulating cTnT and cTnI (cTns) increase following cardiac tissue necrosis, and they are consolidated biomarkers of acute myocardial infarction (AMI). However, the use of high sensitivity (hs)‐immunoassay tests for cTnT and cTnI has made it possible to identify a multitude of other clinical conditions associated with increased circulating levels of cTns. cTns can be measured also in the peripheral circulation of healthy subjects or athletes, suggesting that different mechanisms are involved in the release of cTns in the blood independently of cardiac cell necrosis. In this review, the molecular/cellular mechanisms involved in cTns release in blood and the exploitation of cTnI and cTnT as biomarkers of cardiac adverse events, in addition to cardiac necrosis, are discussed. [ABSTRACT FROM AUTHOR]

Aims: Cardiac amyloidosis (CA) is associated with an elevation of natriuretic peptides and troponins, predicting outcome. Nevertheless, the diagnostic yield of these biomarkers has not been extensively investigated. This study aimed to evaluate the diagnostic performance for CA of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity troponin T (hs‐TnT). Methods and results: Patients with suspected CA (n = 1149) underwent a diagnostic work‐up in three centres in Italy, France (n = 343, derivation cohort), and United Kingdom (n = 806, validation cohort). Biomarker values with either 100% sensitivity or ≥95% specificity were selected as rule‐out/rule‐in cut‐offs, respectively. In the derivation cohort, 227 patients (66%) had CA, and presented with higher NT‐proBNP and hs‐TnT. NT‐proBNP 180 ng/L and hs‐TnT 14 ng/L were selected as rule‐out cut‐offs, and hs‐TnT 86 ng/L as rule‐in cut‐off. NT‐proBNP <180 ng/L or hs‐TnT <14 ng/L were found in 7% of patients, and ruled out CA without false negatives. In the validation cohort, 20% of patients (2% false negatives) had NT‐proBNP <180 ng/L or hs‐TnT <14 ng/L, and 10% showed both biomarkers below cut‐offs (0.5% false negatives). These cut‐offs refined CA prediction when added to echocardiographic scores in patients with a haematologic disease or an increased wall thickness. In the validation cohort, the 86 ng/L hs‐TnT cut‐off ruled in 20% of patients (2% false positives). NT‐proBNP and hs‐TnT cut‐offs retained their rule‐out and rule‐in performance also in cohorts with CA prevalence of 20%, 10%, 5% and 1% derived from the original cohort through bootstrap analysis. Conclusions: Cardiac biomarkers can refine the diagnostic algorithm in patients with suspected CA. NT‐proBNP <180 ng/L and hs‐TnT <14 ng/L reliably exclude the diagnosis, both in the overall population and subgroups referred for either AL‐CA or cardiac (pseudo)hypertrophy. [ABSTRACT FROM AUTHOR]

The term "inflammageing" was introduced in 2000, with the aim of describing the chronic inflammatory state typical of elderly individuals, which is characterized by a combination of elevated levels of inflammatory biomarkers, a high burden of comorbidities, an elevated risk of disability, frailty, and premature death. Inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and rapid progression to heart failure. The great experimental and clinical evidence accumulated in recent years has clearly demonstrated that early detection and counteraction of inflammageing is a promising strategy not only to prevent cardiovascular disease, but also to slow down the progressive decline of health that occurs with ageing. It is conceivable that beneficial effects of counteracting inflammageing should be most effective if implemented in the early stages, when the compensatory capacity of the organism is not completely exhausted. Early interventions and treatments require early diagnosis using reliable and cost-effective biomarkers. Indeed, recent clinical studies have demonstrated that cardiac-specific biomarkers (i.e., cardiac natriuretic peptides and cardiac troponins) are able to identify, even in the general population, the individuals at highest risk of progression to heart failure. However, further clinical studies are needed to better understand the usefulness and cost/benefit ratio of cardiac-specific biomarkers as potential targets in preventive and therapeutic strategies for early detection and counteraction of inflammageing mechanisms and in this way slowing the progressive decline of health that occurs with ageing. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disease (PTLD) is a serious complication occurring as a consequence of immunosuppression in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) or solid organ transplantation (SOT). The majority of PTLD arises from B-cells, and Epstein–Barr virus (EBV) infection is present in 60–80% of the cases, revealing the central role played by the latent infection in the pathogenesis of the disease. Therefore, EBV serological status is considered the most important risk factor associated with PTLDs, together with the depth of T-cell immunosuppression pre- and post-transplant. However, despite the advances in pathogenesis understanding and the introduction of novel treatment options, PTLD arising after alloHSCT remains a particularly challenging disease, and there is a need for consensus on how to treat rituximab-refractory cases. This review aims to explore the pathogenesis, risk factors, and treatment options of PTLD in the alloHSCT setting, finally focusing on adoptive immunotherapy options, namely EBV-specific cytotoxic T-lymphocytes (EBV-CTL) and chimeric antigen receptor T-cells (CAR T). [ABSTRACT FROM AUTHOR]

Simple Summary: Early-onset colorectal cancer (EOCRC) is on the rise. Reasons are unknown and comparative results about long-term survival are still widely debated. This study aimed to explore the effect of early age of onset in a surgical population of sporadic colorectal cancer patients. Early age of onset resulted independently and is associated with worse oncologic outcomes also in stage I patients. This study suggested that EOCRC may have a more aggressive tumoral phenotype compared with late-onset CRC. A better understanding of the biology of EOCRC is needed to revise —and eventually modify—current strategies of treatment and surveillance. The incidence of colorectal cancer (CRC) is increasing in the population aged ≤ 49 (early-onset CRC-EOCRC). Recent studies highlighted the biological and clinical differences between EOCRC and late-onset CRC (LOCRC-age ≥ 50), while comparative results about long-term survival are still debated. This study aimed to investigate whether age of onset may impact on oncologic outcomes in a surgical population of sporadic CRC patients. Patients operated on for sporadic CRC from January 2010 to January 2022 were allocated to the EOCRC and LOCRC groups. The primary endpoint was the recurrence/progression-free survival (R/PFS). A total of 423 EOCRC and 1650 LOCRC was included. EOCRC had a worse R/PFS (p < 0.0001) and cancer specific survival (p < 0.0001) compared with LOCRC. At Cox regression analysis, age of onset, tumoral stage, signet ring cells, extramural/lymphovascular/perineural veins invasion, and neoadjuvant therapy were independent risk factors for R/P. The analysis by tumoral stage showed an increased incidence of recurrence in stage I EOCRC (p = 0.014), and early age of onset was an independent predictor for recurrence (p = 0.035). Early age of onset was an independent predictor for worse prognosis, this effect was stronger in stage I patients suggesting a potentially—and still unknown—more aggressive tumoral phenotype in EOCRC. [ABSTRACT FROM AUTHOR]

Background and purpose: We evaluated the clinical and neurophysiological efficacy of rituximab (RTX) in a neurophysiologically homogeneous group of patients with monoclonal gammopathy and immunoglobulin M (IgM) anti‐myelin‐associated glycoprotein antibody (anti‐MAG) demyelinating polyneuropathy. Methods: Twenty three anti‐MAG‐positive polyneuropathic patients were prospectively evaluated before and for 2 years after treatment with RTX 375 mg/m2. The Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale (INCAT‐ds), modified INCAT sensory score (mISS), Medical Research Council sum score, Patients' Global Impression of Change scale were used, IgM levels were assessed and extensive electrophysiological examinations were performed before (T0) and 1 year (T1) and 2 years (T2) after RTX treatment. Results: At T1 and T2 there was a significant reduction from T0 both in mISS and in INCAT‐ds, with a p value < 0.001 in the inferential Friedman's test overall analysis. Ulnar nerve Terminal Latency Index and distal motor latency significantly changed from T0 to T1 and in the overall analysis (p = 0.001 and p = 0.002), and ulnar nerve sensory nerve action potential (SNAP) amplitude was significantly increased at T2 from T1, with a p value < 0.001 in the overall analysis. Analysis of the receiver‐operating characteristic curves showed that a 41.8% increase in SNAP amplitude in the ulnar nerve at T2 from T0 was a fair predictor of a mISS reduction of ≥2 points (area under the curve 0.85; p = 0.005; sensitivity: 90.9%, specificity: 83.3%). Conclusions: This study suggests that RTX is effective in patients with clinically active demyelinating anti‐MAG neuropathy over 2 years of follow‐up, and that some neurophysiological variables might be useful for monitoring this efficacy. [ABSTRACT FROM AUTHOR]

TMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in response to an increase in intracellular Ca2+. However, the mechanism of how the protein facilitates both processes has remained elusive. Here we investigate the basis for TMEM16F activation. In a screen of residues lining the proposed site of conduction, we identify mutants with strongly activating phenotype. Structures of these mutants determined herein by cryo-electron microscopy show major rearrangements leading to the exposure of hydrophilic patches to the membrane, whose distortion facilitates lipid diffusion. The concomitant opening of a pore promotes ion conduction in the same protein conformation. Our work has revealed a mechanism that is distinct for this branch of the family and that will aid the development of a specific pharmacology for a promising drug target. TMEM16F is a dual ion channel and lipid scramblase that is involved in blood coagulation and cell fusion. Here, authors elucidate how the protein is activated by Ca2+ to accomplish both functions in a single protein conformation. [ABSTRACT FROM AUTHOR]

The article investigates the shielding effectiveness (SE) of a metallic enclosure with a multilayer composite cover over a wide frequency range, from near-field magnetic shielding (1 Hz–1 MHz) to far-field electromagnetic shielding (4–14 GHz). Two enclosures are considered: a conductive enclosure made of aluminum and a magnetic enclosure made of steel. The multilayer composite is a trilayer combining a thin conductive layer of graphene and a thin magnetic layer of a Fe-Ni alloy on either side of a fiberglass plate. To determine the SE of these enclosures in both low-frequency and high-frequency approaches, two experimental setups and two numerical models are developed. The use of the composite cover, instead of the metallic one, gives a similar level of SE in the far-field and a higher specific SE (i.e., SE divided by the material density) in the near-field from 1 Hz to 2 kHz. Such quantitative analysis is the first step to designing practical enclosures entirely covered with composite panels to face electromagnetic compatibility (EMC) constraints in embedded systems. [ABSTRACT FROM AUTHOR]

Major adverse cardiovascular events are frequently observed in patients undergoing major non-cardiac surgery during the peri-operative period. At this time, the possibility to predict cardiovascular events remains limited, despite the introduction of several algorithms to calculate the risk of adverse events, mainly death and major adverse cardiovascular events (MACE) based on the clinical history, risk factors (sex, age, lipid profile, serum creatinine) and non-invasive cardiac exams (electrocardiogram, echocardiogram, stress tests). The cardiac-specific biomarkers natriuretic peptides (NPs) and cardiac troponins (cTn) have been proposed as additional tools for risk prediction in the peri-operative period, particularly for the identification of myocardial injury in patients undergoing major non-cardiac surgery. The prognostic information from the measurement of BNP/NT-proBNP and hs-cTn is independent and complementary to other important indicators of risk, also including ECG and imaging techniques. Elevated levels of cardiac-specific biomarkers before surgery are associated with a markedly higher risk of MACE during the peri-operative period. BNP/NT-proBNP and hs-cTn should be measured in all patients during the clinical evaluation before surgery, particularly during intermediate- or high-risk surgery, in patients aged >65 years and/or with comorbidities. Several questions remain to be assessed in dedicated clinical studies, such as how to optimize the management of patients with raised cardiac specific biomarkers before surgery, and whether a strategy based on biomarker measurement improves patient outcomes and is cost-effective. [ABSTRACT FROM AUTHOR]

Background: Greater efforts are needed to overcome the worldwide reported low achievement of LDL-c targets. This survey aimed to dissect whether and how the physician-based evaluation of patients with diabetes is associated with the achievement of LDL-c targets. Methods: This cross-sectional self-reported survey interviewed physicians working in 67 outpatient services in Italy, collecting records on 2844 patients with diabetes. Each physician reported a median of 47 records (IQR 42–49) and, for each of them, the physician specified its perceived cardiovascular risk, LDL-c targets, and the suggested refinement in lipid-lowering-treatment (LLT). These physician-based evaluations were then compared to recommendations from EAS/EASD guidelines. Results: Collected records were mostly from patients with type 2 diabetes (94%), at very-high (72%) or high-cardiovascular risk (27%). Physician-based assessments of cardiovascular risk and of LDL-c targets, as compared to guidelines recommendation, were misclassified in 34.7% of the records. The misperceived assessment was significantly higher among females and those on primary prevention and was associated with 67% lower odds of achieving guidelines-recommended LDL-c targets (OR 0.33, p < 0.0001). Peripheral artery disease, target organ damage and LLT-initiated by primary-care-physicians were all factors associated with therapeutic-inertia (i.e., lower than expected probability of receiving high-intensity LLT). Physician-suggested LLT refinement was inadequate in 24% of overall records and increased to 38% among subjects on primary prevention and with misclassified cardiovascular risk. Conclusions: This survey highlights the need to improve the physicians' misperceived cardiovascular risk and therapeutic inertia in patients with diabetes to successfully implement guidelines recommendations into everyday clinical practice. [ABSTRACT FROM AUTHOR]