Spatial proteomics in three-dimensional intact specimens.

Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of large biological specimens imaged in 3D are lacking. Here, we present DISCO-MS, a technology that combines whole-organ/whole-organism clearing and imaging, deep-learning-based image analysis, robotic tissue extraction, and ultra-high-sensitivity mass spectrometry. DISCO-MS yielded proteome data indistinguishable from uncleared samples in both rodent and human tissues. We used DISCO-MS to investigate microglia activation along axonal tracts after brain injury and characterized early- and late-stage individual amyloid-beta plaques in a mouse model of Alzheimer's disease. DISCO-bot robotic sample extraction enabled us to study the regional heterogeneity of immune cells in intact mouse bodies and aortic plaques in a complete human heart. DISCO-MS enables unbiased proteome analysis of preclinical and clinical tissues after unbiased imaging of entire specimens in 3D, identifying diagnostic and therapeutic opportunities for complex diseases. VIDEO ABSTRACT.

HLA Gene Polymorphisms in Romanian Patients with Chronic Lymphocytic Leukemia.

Materials and Methods: This study included 66 patients with CLL, diagnosed between 2020 and 2022, and 100 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQA1/DQB1/DPA1/DPB1, and HLA-DRB1/3/4/5) were investigated using next-generation sequencing technology. Results: Several HLA alleles were strongly associated with CLL. The most important finding was that HLA-DRB1∗04:02:01 (p=0.001, OR = 1.05) and HLA-DRB3∗02:01:01 (p=0.009, OR = 1.03) have a predisposing role in CLL development. Moreover, we identified that HLA-A∗24:02:01 0.01 (p=0.01, OR = 0.38), HLA-DQA1∗05:05:01 (p=0.01, OR = 0.56), HLA-DQB1∗03:02:01 (p=0.03, OR = 0.40), and HLA-DRB4∗01:03:01 (p=0.03, OR = 0.54 alleles have protective roles. Correlations between HLA expression and gender showed that women had a higher expression of protective HLA alleles when compared to men. Conclusions: Our data are the first to indicate that in Romanian patients with CLL, the HLA-A∗24:02:01 and HLA-DQA1∗05:05:01 alleles have a protective role against CLL development, whereas HLA-DRB1∗04:02:01 and HLA-DRB3∗02:01:01alleles are positively associated with CLL.

Systemic lupus erythematosus on social networking sites: Friends or foes?

Systemic lupus erythematosus (SLE) is one of the most studied autoimmune diseases. The interest shown for this pathology is translated into international scientific journals, congresses, meetings and, recently, in large data available online. Social networking sites (SNS) have gradually advanced from ways to facilitate interpersonal relations to important sources of information, including medical data regarding SLE, with sites largely accessed by both doctors and patients. Albeit the use of SNS can be valuable in providing education and promoting development of public health, it can be misleading if unprofessional sources of information are used; therefore, both "friends and foes" of the data accessed on large scale should always be considered. This viewpoint is a discussion of the potential benefits and harms related to the SNS use for SLE patients as well as for their physicians.

Systemic lupus erythematosus-related acute pancreatitis.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a complex autoimmune pathology that can involve any organ. Lupus-related acute pancreatitis (AP) is, together with lupus mesenteric vasculitis, an important cause of SLE-induced acute abdominal pain. METHODS: A literature search was conducted using the terms "Pancreatitis" and "Lupus Erythematosus, Systemic" on PubMed/Medline and Web of Science from January 2007 to January 2020. Clinical characteristics, diagnostic approach, and treatment principles in SLE-related AP are presented in this review. RESULTS: Mainly retrospective reports were identified. The reported incidence of SLE-associated AP ranges from 0.9 to more than 5% of patients. A total of 264 SLE patients were found in the selected research, with a net female predominance (sex ratio 9:1) and mean age of 31.4 years. Abdominal pain was virtually present in all cases. AP occurrence was more frequent in SLE patients with short disease duration, high activity scores, and multiorgan involvement. The AP definition was based on currently available guidelines and after exclusion of any other known causes (including iatrogenic, i.e. drugs), a diagnosis of "idiopathic" SLE-related AP might be sustained. Management is difficult, as there is no standardized therapeutic approach. Of note, glucocorticoid use remains still controversial as, especially for high doses, subsequent pancreatic injury may occur. Monitoring serum lipase levels after high dose steroids might be considered. One study reported beneficial prognostic effect of plasma exchange. Moreover, AP in SLE might raise awareness about macrophage activation syndrome association. Mortality up to one third of AP cases in SLE was reported. CONCLUSION: The SLE-related AP is a rare, but severe, life-threatening complication. Corticosteroids must be used with caution. Plasma exchange could be considered in selected cases.

Clinical and histopathological changes in different KIR gene profiles in chronic HCV Romanian patients.

Hepatitis C virus (HCV)-infected individuals may have a faster progression of liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) development when influenced by host, viral and environmental factors. Hepatitis C virus disease progression is also associated with genetic variants of specific killer cell immunoglobulin-like receptors (KIRs) and genes of the major histocompatibility complex (MHC). The aim of the present study was to correlate clinical, virologic and biochemical parameters and to evaluate the possible influence of KIR genes and their HLA class I ligands in patients infected with hepatitis C virus. The present study analysed a total of 127 chronic HCV-infected patients for various biochemical and genetics factors that can influence disease progression and prognosis. Liver function parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), direct bilirubin (DB), alpha-fetoprotein (AFP), HCV RNA levels and fibrosis indices were analysed using well-established biochemical methods. At the same time, KIR and HLA genotyping was performed using a polymerase chain reaction sequence-specific primer technique. Analysis of HLA class I and HLA ligands revealed that HLA-C*12:02 and HLA-A3 and HLA-A11 were positively associated with the F3-F4 fibrosis group (p = .026; OR = 8.717, CI = 1.040-73.077; respectively, p = .047; OR = 2.187; 95% CI = 1.066-4.486). KIR2DL2-positive patients had high median levels of AST after treatment and direct bilirubin levels when compared to KIR2DL2-negative patients (p = .013, respectively, p = .028). KIR2DL2/KIR2DL2-C1C1 genotype was associated with increased AST, ALT and GGT levels. A higher GGT level was also observed in KIR2DS2-C1-positive patients when compared to KIR2DS2-C1-negative patients. The present research demonstrates several links between specific clinical, virologic and biochemical parameters and the expression of KIR genes and their HLA ligands in HCV-infected patients. These connections should be taken into account when considering disease development and treatment.

The impact of the COVID-19 pandemic on patients with primary Sjögren syndrome.

The aim of this study was to investigate the perspective of Romanian patients with Sjögren syndrome (SS) on various aspects of the disease during the SARS-CoV-2 outbreak, including both the impact of COVID-19 on the disease itself as well as the effects of vaccination against SARS-CoV-2 in this group of patients. The study is an online questionnaire-based survey. We received responses from 137 SS patients. Regarding the general emotional status, 33 patients (24.0%) and 47 patients (34.3%) declared to have been sadder/depressive and more agitated/anxious during the SARS-CoV2 outbreak, respectively. During the lockdown, 49 (33.7%) patients strictly and 77 patients (56.2%) did their best to respect the home isolation measures. The income was unchanged for most of the patients (94 patients, 68.6%). Regarding access to healthcare providers, 27 patients (18.7%) postponed the consultation for fear of getting SARS-CoV2. In our study group, 31 patients (22.6%) responded that they have had COVID-19. Only one patient was completely asymptomatic, while the most frequently declared symptom was weakness (84.0%). In 17 patients among the respondents (68%) the symptoms lasted for at least 2 weeks; the most frequent long-lasting symptoms were fatigue (40.0%) and weakness (36.0%). Out of all the respondents, 53 patients (41.4%) were vaccinated against SARS-CoV2 with at least one dose. After the first dose, the most prevalent side effect was pain at the site of injection (89.2%), followed by weakness (25.0%) and myalgias (21.4%). This information will be useful for developing special programs dedicated to SARS-CoV2 infection and vaccination in patients with SS and other autoimmune diseases.

Impaired ankle-brachial index in antiphospholipid syndrome: Beyond the traditional risk factors.

INTRODUCTION: The patients with antiphospholipid syndrome (APS) associate an increased risk of atherosclerosis. OBJECTIVE: To determine the predictors of an abnormal ankle-brachial index (ABI), surrogate measure of atherosclerosis, in patients with APS. METHODS: The ABI was measured according to standard recommendations in 106 patients. Traditional cardiovascular risk factors were assessed in all cases. A large spectrum of APS antibodies was determined in 73 patients. RESULTS: A total of 106 patients diagnosed with APS were included. 28.3% patients included were found to have low ABI. Anti-beta 2-glycoprotein I (aß2GPI) IgG antibodies [4.00 (1.00-79.00) vs 3.00 (0.00-29.00) U/mL, P = 0.02] and antiprothrombin (aPT) IgM antibodies [4.50 (0.00-82.00) vs 3.00 (0.00-14.00) U/mL, P = 0.05] titers were found to be higher in patients with abnormal ABI. However, after multivariate regression analysis, only the aß2GPI IgG titer remained predictor of low ABI (P = 0.04). CONCLUSIONS: aß2GPI IgG associated with impaired ABI in patients with APS. This relation might reflect their involvement in the atherosclerosis occurrence.

The impact of anti-U1-RNP positivity: systemic lupus erythematosus versus mixed connective tissue disease.

Anti-U1-RNP positivity remains mandatory for the mixed connective tissue disease (MCTD) diagnosis, reason for which anti-U1-RNP occurrence in patients with lupus clinical features might determine diagnostic issues. Thus, the prevalence of 25-30% for anti-RNP was reported in John Hopkins and LUMINA lupus cohorts and also 13% prevalence for the anti-U1-RNP in Euro-Lupus cohort. Presence of anti-U1-RNP antibodies in patients fulfilling SLE criteria (but not the MCTD ones) was associated with manifestations such as Raynaud phenomenon, musculoskeletal and lung impairment or nail fold capillaroscopy changes, some clinical features frequently encountered in MCTD patients and only rarely described in lupus population. The use of more specific markers such as 70 kDa anti-U1-RNP or anti-Sm-D was proposed for discriminating between SLE and MCTD. In addition, the IgM serotype of anti-U1-RNP seems more frequently expressed in SLE, while the IgG serotype alone in MCTD. Better acknowledgement of possible clinical involvements in lupus subsets, such as the peculiarities related to the anti-U1-RNP positivity, could provide access to early diagnosis of rather rare but possible severe lupus organ impairments (e.g. pulmonary arterial hypertension).

Influence of decision aids on oral anticoagulant prescribing among physicians: a randomised trial.

BACKGROUND: Oral anticoagulants (OAC) are underused in treatment of atrial fibrillation (AF), with differences in patient and physician preferences. For risk communication, the graphic showing risks on treatment contains all the information, therefore, the graphic showing risks without treatment may not be necessary. Here, our objective was to assess whether decision aids require information of risks without treatment and specifically whether presentation of 5-year stroke risk in patients with AF increases use of OACs compared with presentation of 1-year risk and whether decisions on treatment are different when physicians decide their own treatment vs. that of the patient. DESIGN: Randomised controlled trial with 23 factorial design, performed at 12 university hospitals, one internal medicine course and one national medical conference. RESULTS: Of 968 physicians who participated, 83·3% prescribed anticoagulation therapy. Treatment decisions were not influenced by the number of graphics or by the time frame of risk estimation, with risk differences of 0·5% (95% confidence interval, -4·0% to 5·4%) and 3·4% (-1·3% to 8·1%). However, physician-to-patient prescription rates were 5·4% (0·2-10·6%) more frequent after seeing the 5-year risk graphic. Physician-to-self intentions to prescribe occurred less frequently, with risk difference of 15·4% (10·8-20%). Physicians considered the baseline risk and the absolute risk reduction only when prescribing to patients but not to themselves. CONCLUSIONS: Risks could be communicated using decision aids with only one graphic. Showing the risk of stroke at 5 years could increase the prescription of OACs to patients with AF. Faced with the same risk of stroke, physicians prescribed less to themselves than to patients.

Production networks and resilience: How dense production networks shield economies in financial crisis.

The research delves into the underexplored area of how production network structures influence the severity of economic downturns, particularly during the last financial crisis. Utilizing the RSTAN database from the OECD, we meticulously derived critical measures from the input-output matrices for 61 economies. Our methodology entailed a panel analysis spanning from 2008 to 2010, which is a period marked by significant recessionary pressures. This analysis aimed to correlate economic performance with various production network metrics, taking into account control factors such as interest rates and the prevalence of service sectors. The findings reveal a noteworthy positive correlation between the density of production networks and economic resilience during the crisis, which remained consistent across multiple model specifications. Conversely, as anticipated, higher interest rates were linked to poorer economic performance, highlighting the critical interplay between monetary policy and economic outcomes during periods of financial instability. Given these insights, we propose a policy recommendation emphasizing the strategic enhancement of production network density as a potential buffer against economic downturns. This approach suggests that policymakers should consider the structural aspects of production networks in designing economic stability and growth strategies, thus potentially mitigating the impacts of future financial crises.

Anterior Intercondylar Notch Geometry in Relation to the Native Anterior Cruciate Ligament Size.

BACKGROUND: The intercondylar notch (ICN) and the anterior cruciate ligament (ACL) are important structures in knee morphometry, with key roles in stabilizing the knee. AIM: To determine the associations between the specific shape of the ICN (A-, W-, or U-shape) and the ACL size in patients with intact ACLs. METHODS: Magnetic resonance imaging (MRI) scans were independently analyzed by two experts: one orthopedic surgeon and one imaging physician. In all cases, the following measurements were taken based on the existing definitions: ACL area, anterior ICN (aICN) area, ICN width, lateral trochlear inclination (LTI), and Insall-Salvati index. RESULTS: A total of 65 cases (50.8% male; 33.8 ± 10.2 years mean age at inclusion) were included in the study. The ACL and aICN areas were significantly larger in patients with U-shaped compared with A-shaped and W-shaped ICNs: 0.50 (0.20-0.80) vs. 0.40 (0.20-0.80) vs. 0.40 (0.30-0.80), p = 0.011 and 1.16 (0.57-3.60) vs. 0.47 (0.15-0.95) vs. 0.37 (0.15-0.81), p < 0.001, respectively. Internal meniscal lesions were more common in cases with U-shaped ICNs (64.0%), while external ones were more common in W-shaped ICN cases (35.3%). None of the A-shaped cases had external chondral or meniscal lesions. The ACL area was significantly larger in males and internal meniscal injuries, with no differences between chondral lesions, external meniscal injuries, patellar chondral lesions, patella alta, or trochlear dysplasia. CONCLUSION: The specific shape of the intercondylar notch was associated with the anterior cruciate ligament-anterior intercondylar notch (ACL-aICN) area size correlation, with a strong correlation between ACL and aICN area when the intercondylar notch was A-shaped or W-shaped, and a low correlation when the notch was U- shaped. The specific shape of the intercondylar notch (A-, W-, or U-shape) was associated with the occurrence of both internal and external meniscal injuries, with the U-shaped intercondylar notch morphometry being more frequent in cases with internal meniscal injuries and the W-shape being more common in cases with external meniscal injuries.

Rheumatoid vasculitis in 2023: Changes and challenges since the biologics era.

BACKGROUND: Significant changes in the epidemiology and natural history of rheumatoid vasculitis (RV) have occurred with the introduction of biological therapies such as TNF inhibitors (TNFi) and rituximab. PURPOSE: This scoping review aims to address the key current challenges and propose updated criteria for RV. This will aid future descriptive observational studies and prospective therapeutic trials. METHODOLOGY: The MEDLINE database was searched for eligible articles from inception through December 2022. Articles were selected based on language and publication date after 1998, corresponding to the approval of the first TNFi in rheumatic diseases. RESULTS: Sixty articles were included in the review. The mean incidence of RV has decreased since the approval of biologic therapies in RA, from 9.1 (95% CI: 6.8-12.0) per million between 1988 and 2000 to 3.9 (95% CI: 2.3-6.2) between 2001 and 2010, probably due to significant improvement in RA severity and a decrease in smoking habits. Factors associated with an increased risk of RV include smoking at RA diagnosis, longer disease duration, severe RA, immunopositivity, and male gender (regardless of age). Homozygosity for the HLA-DRB104 shared epitope is linked to RV, while the presence of HLA-C3 is a significant predictor of vasculitis in patients without HLA-DRB104. Cutaneous (65-88%), neurologic (35-63%), and cardiac (33%) manifestations are common in RV, often associated with constitutional symptoms (70%). Histologic findings range from small vessel vasculitis to medium-sized necrotizing arteritis, but definite evidence of vasculitis is not required in the 1984 Scott and Bacon diagnostic criteria. Existing data on RV treatment are retrospective, and no formal published guidelines are currently available. CONCLUSION: The understanding of RV pathogenesis has improved since its initial diagnostic criteria, with a wider range of clinical manifestations identified. However, a validated and updated criteria that incorporates these advances is currently lacking, impeding the development of descriptive observational studies and prospective therapeutic trials. PRIMARY FUNDING SOURCE: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Criteria and Non-Criteria Antiphospholipid Antibodies in Antiphospholipid Syndrome: How Strong Are They Correlated?

The place of non-criteria antiphospholipid antibodies (aPLs) in the diagnosis of antiphospholipid syndrome (APS) is still debatable. The aim of this research was to evaluate the correlations between the titres of non-criteria aPLs (anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and anti-prothrombin (aPT) antibodies), and the ones of the already studied criteria aPLs (anti-cardiolipin (aCL) and anti-ß2 glycoprotein I-aß2GPI antibodies). Altogether, 72 APS (30 primary and 42 secondary) patients were included in our study. High correlation coefficients (rs) were found between aPS IgM and aCL IgM, overall (0.77, p < 0.01), as well as in the primary (0.81, p < 0.01), and secondary (0.75, p < 0.01) APS subgroups. Low or statistically insignificant correlations were observed between IgG/IgM isotypes of aPT and aCL, or aß2GPI, in the entire study population, and when evaluating the subgroups. Therefore, moderate correlations were mainly identified between the tested non-criteria antibodies and the criteria ones, suggesting little added value for the use of the tested non-criteria aPLs, with the exception of aPT, which seems to have different kinetics and might be a promising APS diagnostic tool.

Antiphospholipid Antibodies Occurrence in Acute SARS-CoV-2 Infection without Overt Thrombosis.

We sought to determine the prevalence of antiphospholipid antibodies (aPLs) and their correlation with COVID-19 severity (in terms of clinical and laboratory parameters) in patients without thrombotic events during the early phase of infection. This was a cross-sectional study with the inclusion of hospitalized COVID-19 patients from a single department during the COVID-19 pandemic (April 2020-May 2021). Previous known immune disease or thrombophilia along with long-term anticoagulation and patients with overt arterial or venous thrombosis during SARS-CoV-2 infection were excluded. In all cases, data on four criteria for aPL were collected, namely lupus anticoagulant (LA), IgM and IgG anticardiolipin antibodies (aCL), as well as IgG anti-ß2 glycoprotein I antibodies (aß2GPI). One hundred and seventy-nine COVID-19 patients were included, with a mean age of 59.6 (14.5) years and a sex ratio of 0.8 male: female. LA was positive in 41.9%, while it was strongly positive in 4.5%; aCL IgM was found in 9.5%, aCL IgG in 4.5%, and aß2GPI IgG in 1.7% of the sera tested. Clinical correlation: LA was more frequently expressed in severe COVID-19 cases than in moderate or mild cases (p = 0.027). Laboratory correlation: In univariate analysis, LA levels were correlated with D-dimer (p = 0.016), aPTT (p = 0.001), ferritin (p = 0.012), C-reactive protein (CRP) (p = 0.027), lymphocyte (p = 0.040), and platelet (p < 0.001) counts. However, in the multivariate analysis, only the CRP levels correlated with LA positivity: OR (95% CI) 1.008 (1.001-1.016), p = 0.042. LA was the most common aPL identified in the acute phase of COVID-19 and was correlated with infection severity in patients without overt thrombosis.

Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ's effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

Cardiovascular Disease in Primary Sjögren's Syndrome: Raising Clinicians' Awareness.

In the ever evolving landscape of systemic immune mediated diseases, an increased awareness regarding the associated cardiovascular system impairment has been noted in recent years. Even though primary Sjögren's Syndrome (pSS) is one of the most frequent autoimmune diseases affecting middle-aged individuals, the cardiovascular profile of this specific population is far less studied, at least compared to other autoimmune diseases. Traditional cardiovascular risk factors and disease specific risk factors are inextricably intertwined in this particular case. Therefore, the cardiovascular risk profile in pSS is a multifaceted issue, sometimes difficult to assess. Furthermore, in the era of multimodality imaging, the diagnosis of subclinical myocardial and vascular damage is possible, with recent data pointing that the prevalence of such involvement is higher in pSS than in the general population. Nevertheless, when approaching patients with pSS in terms of cardiovascular diseases, clinicians are often faced with the difficult task of translating data from the literature into their everyday practice. The present review aims to synthesize the existing evidence on pSS associated cardiovascular changes in a clinically relevant manner.

The Predictive Role of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocytes-to-Lymphocyte Ratio (MLR) and Gammaglobulins for the Development of Cutaneous Vasculitis Lesions in Primary Sjögren's Syndrome.

Background: In primary Sjögren's Syndrome (pSS), cutaneous vasculitis lesions (CVL) are extraglandular manifestations with an important clinical and prognostic impact and their early detection might contribute to the improvement of disease control and even patients' survival. The aim of this study was to evaluate the predictive potential of hematological elements in the development of CVL in pSS patients. Methods: In this single center, retrospective study, a total of 245 participants were included (124 pSS patients and 121 healthy controls). Complete blood count, inflammatory and immunological parameters were determined at the initial visit. pSS patients underwent a periodical follow-up program, when disease progression and response to therapy was monitored, including the emergence of CVL. Results: In pSS, leucocytes, lymphocyte, neutrophil, monocyte, erythrocyte and platelet counts are significantly decreased compared to healthy subjects (p < 0.001), whereas cellular ratios: NLR, PLR, MLR, and immunological and inflammatory parameters are significantly increased (p < 0.001). A total of 34 patients with pSS (27.41%) developed CVL during the follow-up period. The occurrence of CVL was positively correlated with neutrophil and platelet counts (p < 0.001), while for lymphocytes the correlation was negative (p < 0.001). Cellular ratios: NLR, PLR and MLR, and gammaglobulins also revealed significant positive correlations with the emergence of CVL in pSS (p < 0.001). The multivariate analysis confirmed the independent predictive character for CVL emergence in pSS for NLR (CI95% 0.053−0.2, p < 0.002), PLR (CI95% 0.001−0.003, p < 0.003), MLR (CI95% 0.086−0.935, p < 0.019), and gammaglobulins (CI95% 0.423−0.688, p < 0.001). Conclusions: Standard hematological parameters, widely used in the assessment of pSS patients, such as NLR, PLR, MLR and gammaglobulins could become valid elements that might be used for the early detection of patients at risk for the development of CVL.

Hydroxychloroquine in systemic and autoimmune diseases: Where are we now?

Hydroxychloroquine (HCQ), one of the oldest drugs used in rheumatology, came recently into attention as one of the potential therapies tested for the severe acute respiratory syndrome coronavirus-2 disease treatment. Used initially as an antimalarial, then translated to rheumatic diseases, HCQ has been used in a wide range of pathologies, including infectious diseases, immune disorders, diabetes, dyslipidemia, or neoplasia. Regarding systemic diseases, HCQ is the mainstay treatment for systemic lupus erythematosus (SLE), where, according to last European guidelines, it is proposed to all SLE patients unless contraindicated or with side effects. HCQ proved positive impact in SLE on robust outcomes, such as accrual damage, disease activity and survival, but also pleiomorphic effects, including decrease in the need for glucocorticoids, reduction in the risk of neonatal lupus, lower fasting glucose and protection against diabetes, thrombotic risk, dyslipidemia, infections, etc. Moreover, HCQ can be used during pregnancy and breast-feeding. Besides SLE, the role for HCQ in the anti-phospholipid syndrome and Sjögren's disease is still under debate. On the contrary, recent advances showed only limited interest for rheumatoid arthritis, especially due the lack of structural damage prevention. There are still no strong data to sustain the HCQ use in other systemic diseases. In this review, we summarised the utility and efficacy of HCQ in different clinical conditions relevant for rheumatology practice.

Diagnostic Application of Volatile Organic Compounds as Potential Biomarkers for Detecting Digestive Neoplasia: A Systematic Review.

Volatile organic compounds (VOCs) are part of the exhaled breath that were proposed as non-invasive breath biomarkers via different human discharge products like saliva, breath, urine, blood, or tissues. Particularly, due to the non-invasive approach, VOCs were considered as potential biomarkers for non-invasive early cancer detection. We herein aimed to review the data over VOCs utility in digestive neoplasia as early diagnosis or monitoring biomarkers. A systematic literature search was done using MEDLINE via PubMed, Cochrane Library, and Thomson Reuters' Web of Science Core Collection. We identified sixteen articles that were included in the final analysis. Based on the current knowledge, we cannot identify a single VOC as a specific non-invasive biomarker for digestive neoplasia. Several combinations of up to twelve VOCs seem promising for accurately detecting some neoplasia types. A combination of different VOCs breath expression are promising tools for digestive neoplasia screening.

Nailfold capillaroscopy in systemic diseases: short overview for internal medicine.

Nailfold capillaroscopy (NFC) is now one of the main imaging tools in systemic sclerosis and imposed over time as an easy, non-invasive method for the nailfold microvascular bed assessment. In qualitative NFC normal pattern is characterized by homogeneous, parallel fashion arrangement of the last capillaries row as well as by capillaries with hairpin or non-specific variations like tortuous and/ or crossing shape. Nailfold capillaroscopy is strongly recommended for evaluation of all patients with Raynaud phenomenon. Appearance of giant capillaries is chronologically the first relevant finding for scleroderma spectrum disorders development (systemic sclerosis, dermatomyositis, undifferentiated and mixed connective tissue disease). Collapses of the giant loops generate microhemorrhages and further capillary loss with subsequent hypoxia, and neoangiogenesis seen as ramified/ bushy capillaries. Nailfold capillaroscopy is indicated especially in systemic sclerosis, being also included in the classification criteria. Based on these major NFC pathologic findings (giant capillaries, microhemorrhages, avascularity and neoangiogenesis), three evolutive stages were described in systemic sclerosis, namely the early, active, and late scleroderma pattern. In other connective tissue diseases than those scleroderma-related, like systemic lupus erythematosus, psoriatic arthritis, or antiphospholipid syndrome, the interest for capillaroscopy is growing, but the attempts of defining specific characteristics failed until now. Besides qualitative NFC, semiquantitative and quantitative capillaroscopic assessments were proposed for more accurate evaluation. Lately, automated systems are under development. There is still need of more studies to sustain the nailfold capillaroscopy validity as diagnostic and prognostic test.