Sarcopenia in gastric cancer: when the loss costs too much

Sarcopenia is a complex syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Malignancy is a major determinant of sarcopenia, and gastric cancer (GC) is among the most common causes of this phenomenon. As sarcopenia is a well-recognized poor prognostic feature in GC and has been associated with worse tolerance of surgical and medical treatments, members of the multidisciplinary team should be aware of the clinical relevance, pathogenic mechanisms, and potential treatments for this syndrome. The importance of sarcopenia is often underestimated in everyday practice and clinical trials, particularly among elderly or fragile patients. As treatment options are improving in all disease stages, deeper knowledge and greater attention to the metabolic balance in GC patients could further increase the benefit of novel therapeutic strategies and dramatically impact on quality of life. In this review, we describe the role of sarcopenia in different phases of GC progression. Our aim is to provide oncologists and surgeons dealing with GC patients with a useful tool for comprehensive assessment and timely management of this potentially life-threatening condition

Rituximab-induced hypogammaglobulinaemia in patients affected by idiopathic inflammatory myopathies: a multicentre study

Objective Rituximab (RTX) is an anti-CD20 chimeric monoclonal antibody recommended as off-label treatment in patients with idiopathic inflammatory myopathies (IIM). The present study aimed to evaluate changes in immunoglobulin (Ig) levels during RTX-treatment and their potential association with infections in a cohort of IIM patients.Methods Patients evaluated in the Myositis clinic belonging to the Rheumatology Units of Siena, Bari and Palermo University Hospitals, and treated for the first time with RTX were enrolled. Demographic, clinical, laboratory and treatment variables, including previous and concomitant immunosuppressive drugs and glucocorticoid (GC) dosage were analysed before (T0) and after 6 (T1) and 12 (T2) months of RTX treatment.Results Thirty patients (median age, IQR 56 (42-66); 22 female) were selected. During the observational period, low levels of IgG (<700 mg/dl) and IgM (<40 mg/dl) occurred in 10% and 17% of patients, respectively. However, no one showed severe (IgG<400 mg/dl) hypogammaglobulinaemia. IgA concentrations were lower at T1 than T0 (p=0.0218), while IgG concentrations were lower at T2 compared to those at baseline (p=0.0335). IgM concentrations were lower at T1 and T2 than T0 (p<0.0001), as well at T2 than T1 (p=0.0215). Three patients suffered major infections, two others had paucisymptomatic COVID-19, one suffered from mild zoster. GC dosages at T0 were inversely correlated with IgA T0 concentrations (p=0.004, r=-0.514). No correlation was found between demographic, clinical and treatment variables and Ig serum levels.Conclusion Hypogammaglobulinaemia following RTX is uncommon in IIM and is not related to any clinical variables, including GC dosage and previous treatments. IgG and IgM monitoring after RTX treatment does not seem useful in stratifying patients who require closer safety monitoring and prevention of infection, due to the lack of association between hypogammaglobulinaemia and the onset of severe infections

Eligibility for vericiguat in a real‐world, contemporary heart failure population

Aims: Vericiguat is a soluble guanylate cyclase stimulator and improves survival in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and an increased risk of decompensation. As real-world data on how many patients could be eligible for vericiguat therapy derive from outdated registries, we aimed to assess eligibility in a prospective cohort of patients with HF. Methods and results: Data from consecutive HF patients undergoing an elective ambulatory visit at five university hospitals from 3 July to 28 July 2023 were collected. Independent investigators assessed which patients (i) met the eligibility criteria of the VICTORIA trial, (ii) complied with HF guideline recommendations, (iii) met regulatory agency criteria, or (iv) met criteria for refundability according to the Italian regulatory agency. Patients (n = 346, 72% men, median age 69 years) had HFrEF in 57% of cases, left ventricular ejection fraction < 45% in 68%, and New York Heart Association class II-IV symptoms in 76%. Patients meeting the eligibility criteria of the VICTORIA trial or European and American HF Guideline recommendations were 9% and 13%, respectively. Patients meeting Food and Drug Administration (FDA) or European Medicines Agency (EMA) label criteria were 19% and 17%, respectively. Drug costs would be covered by the Italian National Health System in 10% of patients [if a sodium-glucose cotransporter-2 inhibitor (SGLT2i) is not mandatory] or in 8% (if an SGLT2i is requested). Conclusions: In a real-world study, 9% of patients met the eligibility criteria of the VICTORIA trial, but up to 13% complied with guideline recommendations and up to 19% met FDA or EMA criteria. In Italy, drug costs would be covered by up to 10% of patients

Relationship between immune response to SARS-CoV2 vaccines and development of breakthrough infection in solid organ transplant recipients: the CONTRAST cohort

Background: SARS-CoV-2 vaccination in solid organ transplant (SOT) is associated with poorer antibody response (AbR) compared to non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) should yet be assessed. Methods: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV2 vaccination during 1-year period from February 2021, and followed-up to April 30th 2022. Patients were tested for AbR at multiple timepoints. Primary endpoint was BI (laboratory confirmed SARS-CoV2 infection ≥14 days after 2nd dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization and BI states were obtained for each type of graft and vaccination sequence with multistate survival analysis, then multivariable logistic regression was performed to analyse the risk of BI in AbR levels. Results: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received three vaccine doses, the first two consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively; while at the third dose mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed lowest probability of immunization (0.418) and highest of BI (0.323), all-mRNA-1273 vaccine-sequence showed higher probability of immunization (0.732) and lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age and shorter time from transplant. Conclusions: SOT patients with non-high-level AbR, shorter time from transplantation, and heart recipients are at highest risk of BI

Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes

OBJECTIVE: Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring. METHODS: The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018. RESULTS: Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels <0.64 mEq/L and dosages <600 mg/day had more reactive newborns without an increased risk of cardiac malformations. CONCLUSIONS: The risk associated with lithium exposure at any time during pregnancy is low, and the risk is higher for first-trimester or higher-dosage exposure. Ideally, pregnancy should be planned during remission from bipolar disorder and lithium prescribed within the lowest therapeutic range throughout pregnancy, particularly during the first trimester and the days immediately preceding delivery, balancing the safety and efficacy profile for the individual patient

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted&nbsp;an umbrella review (protocol&nbsp; link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and&nbsp;quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders

Evidence-Based Umbrella Review of 162 Peripheral Biomarkers for Major Mental Disorders

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer’s disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum TimeCourse

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.This research was partially funded by FOREUM—Foundation for Research in Rheumatolog