Survival Outcome Prediction in Glioblastoma: Insights from MRI Radiomics.

Background: Extracting multiregional radiomic features from multiparametric MRI for predicting pretreatment survival in isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) patients is a promising approach. Methods: MRI data from 49 IDH wild-type glioblastoma patients pre-treatment were utilized. Diffusion and perfusion maps were generated, and tumor subregions segmented. Radiomic features were extracted for each tissue type and map. Feature selection on 1862 radiomic features identified 25 significant features. The Cox proportional-hazards model with LASSO regularization was used to perform survival analysis. Internal and external validation used a 38-patient training cohort and an 11-patient validation cohort. Statistical significance was set at p < 0.05. Results: Age and six radiomic features (shape and first and second order) from T1W, diffusion, and perfusion maps contributed to the final model. Findings suggest that a small necrotic subregion, inhomogeneous vascularization in the solid non-enhancing subregion, and edema-related tissue damage in the enhancing and edema subregions are linked to poor survival. The model's C-Index was 0.66 (95% C.I. 0.54-0.80). External validation demonstrated good accuracy (AUC > 0.65) at all time points. Conclusions: Radiomics analysis, utilizing segmented perfusion and diffusion maps, provide predictive indicators of survival in IDH wild-type glioblastoma patients, revealing associations with microstructural and vascular heterogeneity in the tumor.

Pituitary gland height evaluated with magnetic resonance imaging in premature twins: the impact of growth and sex.

BACKGROUND: Pituitary gland height reflects secretory activity of the hypothalamo-pituitary axis. OBJECTIVE: To assess the cumulative impact of fetal growth and sex on pituitary gland height in premature twins, dissociated from prematurity. MATERIALS AND METHODS: A retrospective study was conducted, assessing the pituitary gland height in 63 pairs of preterm twins, measured from T1-weighted magnetic resonance imaging (MRI). Auxological parameters, including body weight, body length, and head circumference, at birth and at the time of MRI, were used as proxies for fetal and postnatal growth, respectively. The study population was divided into two groups, using corrected age at around term equivalent as the cutoff point. Statistical analysis was performed using mixed-effects linear regression models. RESULTS: When pituitary gland height was evaluated at around term equivalent, a greater pituitary gland height, suggesting a more immature hypothamo-pituitary axis, was associated with the twin exhibiting lower auxological data at birth. The same association was observed when body weight and length at MRI were used as covariants. In the group evaluated after term equivalent, a smaller pituitary gland height, suggesting a more mature hypothamo-pituitary axis, was associated with male sex. This difference was observed in twin pairs with higher average body weight at birth, and in babies exhibiting higher auxological data at MRI. CONCLUSION: After isolating the effect of prematurity, at around term equivalent, pituitary gland height reflects the cumulative impact of fetal growth on the hypothalamo-pituitary axis. Subsequently, pituitary gland height shows effects of sex and of fetal and postnatal growth.

Sjögren's syndrome: one year in review 2023.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterised by the T-cell-mediated hyperactivation of B-cells and cytokine production. The condition may evolve from an asymptomatic, indolent course, with glandular involvement, to extra-glandular systemic manifestations up to lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T- and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. Recently, increasing research focused on the investigation of mechanisms underlying the complex pathogenesis of the disease and highlighted the multi-factorial nature of SS consisting of concomitant involvement of environmental, genetic, neuroendocrine and immune factors. In particular, many aspects have been investigated regarding genetic and epigenetics, the role of specific B- and T-cell phenotypes and the investigation of disease-specific biomarkers as predictors of disease development, activity, and lymphomagenesis. Surely, a deeper understanding of these multiple mechanisms may facilitate earlier diagnosis, enable subphenotyping of patients and open novel therapeutic possibilities to address the unmet needs of the disease in the upcoming years.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.

Impact of gender and age at onset on Sjögren's syndrome presentation and outcome: state of the art.

Sjögren's syndrome (SS) is a complex and heterogeneous disease that typically affects middle-aged women. However, while it is rare, the disease may occur in male patients and in females during their childhood/adolescence or in the elderly. Contrasting data have been reported on these three subgroups clinical features and long-term outcomes. Notably, recent studies have pinpointed the severity of the disease in male patients and in both the early and the late-onset subgroups.The aim of this review is, therefore, to summarise the available evidence from the recent literature on these phenotypes. The focus will be on the clinical and laboratory features, and on the lymphoma risk observed in the three subgroups distinct phenotypes: of male patients as well as young-onset SS and elderly-onset SS. Ultimately, an accurate phenotypic stratification may represent the first step towards individualised medical approaches.

The role of ventral tegmental area in chronic stroke rehabilitation: an exploratory study.

Introduction: The acknowledged role of external rewards in chronic stroke rehabilitation, offering positive reinforcement and motivation, has significantly contributed to patient engagement and perseverance. However, the exploration of self-reward's importance in this context remains limited. This study aims to investigate the functional connectivity of the ventral tegmental area (VTA), a key node in the brain's reward circuitry, during motor task-based rehabilitation and its correlation with the recovery process. Methods: Twelve right-handed healthy volunteers (4 men, 8 women, aged 57.4 ± 11.3 years) and twelve chronic stroke patients (5 men, 7 women, aged 48.1 ± 11.1 years) with clinically significant right-sided motor impairment (mean FM-UE score of 27.6 ± 8.7) participated. The analysis employed the CONN toolbox to assess the association between motor tasks and VTA connectivity using psychophysiological interaction (PPI). Results: PPI analysis revealed motor-dependent changes in VTA connectivity, particularly with regions within the motor circuitry, cerebellum, and prefrontal cortex. Notably, stronger connectivity between the ipsilesional VTA and cerebellum was observed in healthy controls compared to chronic stroke patients, highlighting the importance of VTA-cerebellum interactions in motor function. Stroke patients' motor performance was associated with VTA modulation in areas related to both motor tasks and reward processing, emphasizing the role of self-reward processes in rehabilitation. Changes in VTA influence on motor circuitry were linked to improvements in motor performance resulting from rehabilitation. Discussion: Our findings underscore the potential of neuroimaging techniques in quantifying and predicting rehabilitation outcomes by examining self-reward processes. The observed associations between VTA connectivity and motor performance in both healthy and stroke-affected individuals emphasize the role of psychological factors, particularly self-reward, in the rehabilitation process. This study contributes valuable insights into the intricate interplay between reward circuits and motor function, highlighting the importance of addressing psychological dimensions in neurorehabilitation strategies.

The Australasian dingo archetype: de novo chromosome-length genome assembly, DNA methylome, and cranial morphology.

BACKGROUND: One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long-read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed. FINDINGS: We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on chromosomes 11, 16, 25, and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and 9 previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mitochondrial DNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified 2 differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphologic data, comprising geometric morphometric assessment of cranial morphology, place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue shows she had a larger cranial capacity than a similar-sized domestic dog. CONCLUSIONS: These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphologic characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney.

The Australasian dingo archetype: De novo chromosome-length genome assembly, DNA methylome, and cranial morphology.

Background: One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed. Findings: We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on Chromosomes 11, 16, 25 and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and nine previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mtDNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified two differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphological data, comprising geometric morphometric assessment of cranial morphology place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue show she had a larger cranial capacity than a similar-sized domestic dog. Conclusions: These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphological characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney.

Predicting lymphoma in Sjögren's syndrome and the pathogenetic role of parotid microenvironment through precise parotid swelling recording.

OBJECTIVE: Parotid swelling (PSW) is a major predictor of non-Hodgkin's lymphoma (NHL) in primary SS (pSS). However, since detailed information on the time of onset and duration of PSW is scarce, this was investigated to verify whether it may lead to further improved prediction. NHL localization was concomitantly studied to evaluate the role of the parotid gland microenvironment in pSS-related lymphomagenesis. METHODS: A multicentre study was conducted among patients with pSS who developed B cell NHL during follow-up and matched controls that did not develop NHL. The study focused on the history of salivary gland and lachrymal gland swelling, evaluated in detail at different times and for different durations, and on the localization of NHL at onset. RESULTS: PSW was significantly more frequent among the cases: at the time of first referred pSS symptoms before diagnosis, at diagnosis and from pSS diagnosis to NHL. The duration of PSW was evaluated starting from pSS diagnosis, and the NHL risk increased from PSW of 2-12 months to >12 months. NHL was prevalently localized in the parotid glands of the cases. CONCLUSION: A more precise clinical recording of PSW can improve lymphoma prediction in pSS. PSW as a very early symptom is a predictor, and a longer duration of PSW is associated with a higher risk of NHL. Since lymphoma usually localizes in the parotid glands, and not in the other salivary or lachrymal glands, the parotid microenvironment appears to be involved in the whole history of pSS and related lymphomagenesis.

The clinical phenotype of primary Sjögren's syndrome patients with lymphadenopathy.

OBJECTIVES: Previous cohort studies have shown that around 10% of patients with primary Sjögren's syndrome (pSS) develop lymphadenopathy during their disease course. However, no studies have described their clinical phenotype. The present study aims to describe the clinical manifestations and laboratory findings of pSS patients presenting long-standing lymphadenopathy. METHODS: From a total of 1234 consecutive pSS patients fulfilling the 2016 ACR-EULAR criteria, those with stable lymphadenopathy unrelated to lymphoma were identified (lymphadenopathy group). Their clinical data were collected and compared with 2 control groups: a) the remaining unmatched pSS patients without lymphadenopathy (unmatched non-lymphadenopathy group) and b) pSS patients without lymphadenopathy matched for age, sex, and disease duration, in an approximately 1:1 ratio (matched non-lymphadenopathy group). RESULTS: One hundred and sixty-five (13.37%) patients presented persistent, stable lymphadenopathy. They were characterised by younger age at both pSS onset and diagnosis, and by shorter disease duration. Compared to the unmatched nonlymphadenopathy group, patients with lymphadenopathy had more frequently salivary gland enlargement (p<0.001), higher focus score at first salivary gland biopsy (p=0.017), palpable purpura (p<0.001), peripheral nervous system involvement (p=0.012), glomerulonephritis (p<0.001), and leukopenia (p<0.001), while the results of the matched comparison were similar. Regarding the serological profile, the comparison with the unmatched group demonstrated higher frequency of ANA (p=0.013), anti-Ro/SSA (p=0.001), and anti-La/SSB (p<0.001) positivity for the lymphadenopathy group, while in the matched comparison only higher rates of anti-Ro/SSA positivity (p=0.002) remained statistically significant. CONCLUSIONS: pSS patients presenting non-lymphoma related stable lymphadenopathy constitute a subgroup of younger individuals with B-cell hyperactivation.

Sjögren's syndrome: one year in review 2022.

Primary Sjögren's syndrome (pSS) is a complex disabling systemic autoimmune disorder. The hallmark of pSS is the T-cell-mediated hyperactivation of B-cells, evolving from asymptomatic conditions to systemic complications and lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T- and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. B-cells show multiple possible roles in disease pathogenesis, from autoantibody production, to antigen presentation, and cytokine production. B-cells hyperactivation is supported by genetic risk factors, T-cell dependent and independent mechanisms, and the presence of different pathogenic B-cell subsets must be reminded.Many aspects have been investigated in the last year regarding genetic and epigenetics, B- and T-cell role in pSS pathogenesis, their interaction with salivary gland epithelial cells (SGECs) and in their direct or indirect use as biomarkers and predictors of disease development, activity, and lymphomagenesis.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.

Clinical and laboratory findings of primary Sjögren's syndrome patients without sicca symptoms.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by oral and eye dryness. A minority of patients can present without dryness but studies on their clinico-laboratory manifestations are scarce. Our purpose was to describe the clinical phenotype of pSS patients lacking sicca symptoms. METHODS: From a total of 1738 consecutive pSS patients fulfilling the 2016 ACR-EULAR criteria, those who presented without sicca symptoms were identified (non-dryness group). Their medical data was collected and compared with 2 control groups: a) the remaining unmatched sicca pSS patients with both oral and eye dryness (unmatched dryness group) and b) matched sicca pSS patients according to age, sex, and disease duration, in 1:2 ratio (matched dryness group). RESULTS: Thirty-eight (2.19%) patients lacked sicca manifestations presenting mainly with arthralgias (47%), parotid enlargement (24%), Raynaud's phenomenon (11%) and persistent lymphadenopathy (11%) that led them to be evaluated for pSS. Non-dryness pSS patients were younger than the unmatched sicca controls, displaying a higher frequency of anti-Ro/SSA antibodies (100% vs. 79.7%, p<0.001), ANA positivity (100% vs. 90.4%, p<0.001), neutropenia (20.8% vs. 7.5%, p=0.04) and thrombocytopenia (13.8% vs. 4.2%, p=0.04). They also had lower frequency of positive ocular tests compared to both unmatched and matched dryness patients. No differences were found between non-dryness pSS patients and both control groups regarding focus score or any other extraglandular manifestation. CONCLUSIONS: pSS patients without sicca complaints constitute a distinct phenotype involving younger patients, sharing common immunopathologic mechanisms with typical sicca patients.

The Severity of Sensorimotor Tracts Degeneration May Predict Motor Performance in Chronic Stroke Patients, While Brain Structural Network Dysfunction May Not.

Although the relationship between corticospinal tract (CST) fiber degeneration and motor outcome after stroke has been established, the relationship of sensorimotor cortical areas with CST fibers has not been clarified. Also limited research has been conducted on how abnormalities in brain structural networks are related to motor recovery. To address these gaps in knowledge, we conducted a diffusion tensor imaging (DTI) study with 12 chronic stroke patients (CSPs) and 12 age-matched healthy controls (HCs). We compared fractional anisotropy (FA) and mean diffusivity (MD) in 60 CST segments using the probabilistic sensorimotor area tract template (SMATT). Least Absolute Shrinkage and Selection Operator (LASSO) regressions were used to select independent predictors of Fugl-Meyer upper extremity (FM-UE) scores among FA and MD values of SMATT regions. The Graph Theoretical Network Analysis Toolbox was used to assess the structural network of each subject's brain. Global and nodal metrics were calculated, compared between the groups, and correlated with FM-UE scores. Mann-Whitney U-tests revealed reduced FA values in CSPs, compared to HCs, in many ipsilesional SMATT regions and in two contralesional regions. Mean FA value of the left (L.) primary motor cortex (M1)/supplementary motor area (SMA) region was predictive of FM-UE score (P = 0.004). Mean MD values for the L. M1/ventral premotor cortex (PMv) region (P = 0.001) and L. PMv/SMA region (P = 0.001) were found to be significant predictors of FM-UE scores. Network efficiency was the only global metric found to be reduced in CSPs (P = 0.006 vs. HCs). Nodal efficiency of the L. hippocampus, L. parahippocampal gyrus, L. fusiform gyrus (P = 0.001), and nodal local efficiency of the L. supramarginal gyrus (P < 0.001) were reduced in CSPs relative to HCs. No graph metric was associated with FM-UE scores. In conclusion, the integrity of CSTs connected to M1, SMA, and PMv were shown to be independent predictors of motor performance in CSPs, while stroke-induced topological changes in the brain's structural connectome may not be. A sensorimotor cortex-specific tract template can refine CST degeneration data and the relationship of CST degeneration with motor performance.

Volumetric apparent diffusion coefficient histogram analysis of the testes in nonobstructive azoospermia: a noninvasive fingerprint of impaired spermatogenesis?

OBJECTIVES: To explore the association between testicular volumetric apparent diffusion coefficient (ADC) histogram analysis metrics and histologic categories in nonobstructive azoospermia (NOA). The role of ADC histogram analysis in predicting the presence of spermatozoa, prior to testicular sperm extraction (TESE), was also investigated. METHODS: Forty-one NOA men and 17 age-matched controls underwent scrotal MRI with diffusion-weighted imaging. Histogram analysis of ADC data of the whole testis was performed. Metrics including mean, standard deviation, median, mode, 25th percentile, 75th percentile, skewness, kurtosis, and entropy of volumetric ADC histograms were calculated. Nonparametric statistical tests were used to assess differences in ADC histogram parameters between NOA histologic categories (hypospermatogenesis, severe hypospermatogenesis, early maturation arrest, and Sertoli cell-only syndrome) and normal testes and, between NOA with positive and negative sperm retrieval. RESULTS: Normal testes had a lower mean, median, mode, 25th percentile (p < 0.001), and 75th percentile of ADC (p = 0.001), compared to NOA histologic phenotypes. NOA with hypospermatogenesis had a lower 25th percentile of ADC compared to NOA with severe hypospermatogenesis. Regression analysis revealed that the 25th percentile of ADC had a moderately negative correlation with NOA histologic phenotype. The median ADC proved the most significant metric (p = 0.007) to predict the presence of sperm. CONCLUSIONS: Testicular volumetric ADC histogram parameters may contribute in the identification of the subpopulation of NOA men with a specific type of spermatogenic arrest. KEY POINTS: • Volumetric ADC histogram analysis metrics may be used as noninvasive markers of impaired spermatogenesis in nonobstructive azoospermia. • The 25th percentile of ADC proved useful in discriminating between NOA testes with hypospermatogenesis and severe hypospermatogenesis. • The median ADC proved the most significant parameter to predict the presence of viable spermatozoa prior to TESE.

Patient-centered approaches for patients with systemic autoimmune rheumatic diseases: development and evolution.

INTRODUCTION: European Reference Networks (ERNs) are dedicated to rare complex diseases. Systemic autoimmune rheumatic diseases (SARDs) comprise a group of disorders, some of which are rare, complex, and chronic, characterized by relapsing-remitting course and requiring targeted treatments for long periods; SARDs are also associated with various co-morbidities and therefore health-care infrastructures, at the highest level of expertise are required. AREAS COVERED: For the current work, literature on the basic characteristics of a center of excellence dedicated to SARDs, its advantages over the existing health infrastructures in order to improve health and social care, its contribution to the education of health-care workers, and the related research opportunities are presented. In addition, our experience, vision, and initiatives as a new member of the ERNs are reported. EXPERT OPINION: A restructure in healthcare policy and resource allocation, based on centers of expertise, is necessary to improve the medical care of patients with SARDs.

Structural and functional brain connectivity in moderate-late preterm infants with low-grade intraventricular hemorrhage.

PURPOSE: Brain functional connectivity (FC) changes and microstructural abnormalities are reported in infants born moderate and late preterm (MLPT). We evaluated the effect of low-grade (grades I, II) intraventricular hemorrhage (IVH) in MLPT babies on brain structural connectivity (SC) and FC. METHODS: Babies born MLPT between January 2014 and May 2017 underwent brain ultrasound (US) at 72 h and 7 days after birth, and MRI at around term equivalent. The MRI protocol comprised T1- and T2-weighted sequences, diffusion tensor imaging (DTI), and resting-state functional MRI (fMRI). SC and FC were assessed using graph analysis. RESULTS: Of 350 MLPT neonates, 15 showed low-grade IVH on US at 72 h, for which brain MRI was available in 10. These 10 infants, with mean gestational age (GA) 34.0 ± 0.8 weeks, comprised the study group, and 10 MLPT infants of mean GA 33.9 ± 1.1 weeks, with no abnormalities on brain US and MRI, were control subjects. All study subjects presented modularity, small world topology, and rich club organization for both SC and FC. The patients with low-grade IVH had lower FC rich club coefficient and lower SC betweenness centrality in the left frontoparietal operculum, and lower SC rich club coefficient in the right superior orbitofrontal cortex than the control subjects. CONCLUSIONS: Topological and functional properties of mature brain connectivity are present in MLPT infants. IVH in these infants was associated with structural and functional abnormalities in the left frontoparietal operculum and right orbitofrontal cortex, regions related to language and cognition.

Clinical picture, outcome and predictive factors of lymphoma in primary Sjögren's syndrome: results from a harmonized dataset (1981-2021).

OBJECTIVES: Primary Sjögren's Syndrome (pSS) carries the highest risk for non-Hodgkin's lymphoma (NHL) development among systemic autoimmune diseases. However, the paucity of data on the long-term survival of those patients and the lack of established predictors for each lymphoma histologic subtype prompted our present study. METHODS: We retrospectively analysed 121 patients diagnosed with NHL according to the WHO classification criteria. All patients fulfilled the 2016 ACR-EULAR classification criteria for pSS. Cumulative clinical, laboratory, radiologic, treatment regimens and histologic data were recorded, harmonized and analysed. Overall survival (OS) and event-free survival (EFS) curves were calculated. A mucosa-associated lymphoid tissue lymphoma (MALTL) prediction model was developed by applying innovative data-driven analysis of clinical features present at the time of pSS diagnosis. RESULTS: MALTLs constituted the majority of lymphomas (92/121, 76.0%) followed by diffuse large B-cell lymphomas (DLBCL) (11/121, 9.0%) and nodal marginal zone lymphomas (NMZL) (8/121, 7%). MALTLs show salivary glands localization, limited disease and often bone marrow and nodal involvement. The 10-year OS and EFS rates were 79% and 45.5% for MALTLs, 40.9% and 24.2% for DLBCL and 46% and 31% for NMZL. Cryoglobulinemia, focus score and the total EULAR SS Disease Activity Index (ESSDAI) composite index at pSS diagnosis were proven independent MALTL predictors. Even though MALTLs have a comparatively good survival outlook, they are accompanied by frequent events throughout their clinical course. CONCLUSIONS: Common features of pSS, present at diagnosis, can predict future lymphomagenesis meriting a more intensive follow-up plan.

One year in review 2021: Sjögren's syndrome.

Sjögren's syndrome (SS) is a multifactorial systemic autoimmune disease of unknown aetiology characterised by a wide spectrum of different clinical manifestations and scattered complications. Recently, great efforts have been made to elucidate mechanisms involved in the pathogenesis of the disease in order to identify exploitable therapeutic targets in SS. Similarly, novel insights have enabled to better define disease phenotypes and different outcomes. Ultimately, the discovery of new potential therapeutic targets and a better stratification of patients are paving new avenues for novel treatment options and treat-to-target therapeutic approach. In this review, we will provide a critical digest of the recent literature published in 2020 on SS pathogenesis, clinical manifestations and novel treatment options.

A prospective multicenter study assessing humoral immunogenicity and safety of the mRNA SARS-CoV-2 vaccines in Greek patients with systemic autoimmune and autoinflammatory rheumatic diseases.

OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.