Generation and External Validation of a Histologic Transformation Risk Model for Patients with Follicular Lymphoma.

Follicular lymphoma (FL) is the most frequent indolent lymphoma. Some patients (10%-15%) experience histologic transformation (HT) to a more aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). This study aimed to validate and improve a genetic risk model to predict HT at diagnosis.We collected mutational data from diagnosis biopsies of 64 FL patients. We combined them with the data from a previously published cohort (total n = 104; 62 from nontransformed and 42 from patients who did transform to DLBCL). This combined cohort was used to develop a nomogram to estimate the risk of HT. Prognostic mutated genes and clinical variables were assessed using Cox regression analysis to generate a risk model. The model was internally validated by bootstrapping and externally validated in an independent cohort. Its performance was evaluated using a concordance index and a calibration curve. The clinicogenetic nomogram included the mutational status of 3 genes (HIST1HE1, KMT2D, and TNFSR14) and high-risk Follicular Lymphoma International Prognostic Index and predicted HT with a concordance index of 0.746. Patients were classified as being at low or high risk of transformation. The probability HT function at 24 months was 0.90 in the low-risk group vs 0.51 in the high-risk group and, at 60 months, 0.71 vs 0.15, respectively. In the external validation cohort, the probability HT function in the low-risk group was 0.86 vs 0.54 in the high-risk group at 24 months, and 0.71 vs 0.32 at 60 months. The concordance index in the external cohort was 0.552. In conclusion, we propose a clinicogenetic risk model to predict FL HT to DLBLC, combining genetic alterations in HIST1H1E, KMT2D, and TNFRSF14 genes and clinical features (Follicular Lymphoma International Prognostic Index) at diagnosis. This model could improve the management of FL patients and allow treatment strategies that would prevent or delay transformation.

Influence of rheumatoid factor on serum drug levels of TNF inhibitors with different structures in rheumatoid arthritis.

OBJECTIVES: Certolizumab pegol (CZP), an Fc-free antibody fragment, has shown stable serum levels and steady efficacy in the treatment of RA patients, irrespective of RF levels at baseline. Here, we examine, in clinical practice, the effect of baseline RF and ACPA levels on serum drug levels of IFX, ADL and CZP an Fc-free antibody fragment. METHODS: This is a retrospective study performed in real-world patients. We assessed 170 patients with RA: 90 (53%) received IFX, 48 (28%) ADL and 32 (19%) CZP. Demographic and clinical variables, RF and ACPA levels were obtained at the baseline visit (T0), and patients were stratified based on negative, low, medium, or high levels. After 6 months (T6) serum drug levels and anti-drug antibodies (ADAb), were computed. RESULTS: While CZP serum levels did not differ across RF groups at T6, high baseline RF was linked to lower serum drug levels compared to RF negative status in treatment with complete monoclonal antibodies IFX and ADL. No differences in disease activity measured by DAS28 at baseline were observed across RF quartiles in patients treated with IFX or ADL. ADAb was observed in 26 patients with IFX, 3 with ADL and 1 with CZP, following 6 months of treatment. Patients with high baseline RF levels dropped out more frequently by secondary non-response in IFX or ADL than CZP (80% vs. 75% vs. 33%, p=0.002). CONCLUSIONS: In this real word data evaluation, CZP serum levels were independent of RF levels in patients however patients with high baseline RF levels who obtained IFX or ADL had lower serum drug levels at 6 months than baseline RF-negative patients. In addition, secondary non-response was more frequent in patients with high RF levels treated with IFX and ADL.

NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells.

Introduction: Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation. Methods: In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells' cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality. Results: In vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells. Discussion: The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.

An In Vitro Study to Assess the Best Strategy for the Chemical Debridement of Periprosthetic Joint Infection.

Irrigation and debridement using an irrigation solution is a fundamental step during the surgical treatment of both acute and chronic periprosthetic joint infection (PJI). However, there is no consensus on the optimal solution, nor is there sufficient evidence on the optimal irrigation time and combination of solutions. Therefore, it is necessary to determine which solution or combination of solutions is most efficacious against biofilm, as well as the optimal irrigation time. We conducted an experimental in vitro model by inoculating stainless steel discs with ATCC strains of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and a clinical strain of Staphylococcus epidermidis. The discs were all irrigated with commonly used antiseptic solutions (10% and 3% povidone iodine, hydrogen peroxide, 3% acetic acid, and Bactisure™) for 1 min, 3 min, and 5 min and their combinations for 9 min (3 min each) vs. sterile saline as a positive control. We evaluated the reduction in biofilm based on colony-forming unit (cfu) counts and in combination assays, also based on cell viability and scanning electron microscopy. All antiseptics alone reduced more than 90% of cfu counts after 1 min of irrigation; the worst results were for hydrogen peroxide and 3% acetic acid. When solutions were sequentially combined, the best results were observed for all those starting with acetic acid, in terms of both reduction of log cfu/mL counts and viable cells. We consider that a combination of antiseptic solutions, particularly that comprising the sequence acetic acid + povidone iodine + hydrogen peroxide, would be the best option for chemical debridement during PJI surgery.

Ultrasonography in the diagnosis of suspected primary Sjögren's syndrome and concordance with salivary gland biopsy: a Spanish single-center study.

OBJECTIVE: The study aims to evaluate the utility of major salivary gland ultrasonography for diagnosis of primary Sjögren's syndrome (pSS) and to assess its concordance with minor salivary gland biopsy (MSGB). METHODS: A cross-sectional study of 72 patients with suspected pSS was performed. Demographic, clinical, and serological data were collected. MSGB was performed, as was ultrasonography. The ultrasound technician was blind to clinical, serological, and histological data. The validity of ultrasonography compared with MSGB, the American-European Consensus Group (AECG), and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria was assessed by calculating the percentage of agreement, sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC). RESULTS: Based on MSGB as the gold standard, the percentage of agreement between both tests was 78% (AUC 0.75). Based on the ACR/EULAR criteria, the percentage of agreement was 83% (AUC 0.78) for ultrasonography and 81% (AUC 0.83) for biopsy. Sensitivity and specificity were 90% and 67%, respectively, for ultrasonography and 76% and 90% for biopsy. The results were similar with the AECG criteria. The intra- and inter-observer variability was good (κ > 0.7). Significant differences were observed for positive anti-Ro52 values and hypergammaglobulinemia in pathological ultrasound scans. CONCLUSION: Diagnostic ultrasonography is as useful as MSGB in pSS. Therefore, it could be included in the classification criteria. In this cohort, it proved more sensitive than MSGB and could be used as an initial test for patients suspected of having pSS. MSGB could be used in cases where clinical and serological results are inconclusive. Key Points • Major salivary gland ultrasonography adds diagnostic value similar to that of MSGB, thus potentially enabling this invasive procedure to be avoided. • Ultrasonography could be included in the classification criteria for primary Sjögren's syndrome. • Given that ultrasonography is more sensitive and less specific than MSGB, it could be used as an initial diagnostic test in patients with suspected Sjögren's syndrome. • Biopsy should be performed in those cases where ultrasonography, clinical, and serological data are inconclusive.

Median nerve compression at elbow level by a proximal cubital artery pseudoaneurysm: a case report

We describe the case of an 82-year-old man who had recently undergone cardiac surgery (quadruple coronary bypass), who consulted due to the appearance of a necrotic eschar on the thumb of the right index finger, together with paraesthesia and hypoaesthesia in the first 3 fingers of the same hand. An ultrasound scan of the right elbow was performed to rule out involvement of the median nerve and an anechoic, thick-walled mass was found, dependent on the wall of the proximal ulnar artery, compatible with a pseudoaneurysm of the same, compressing the nerve. Electromyography showed an acute lesion of the proximal median nerve and angio-CT confirmed the diagnosis of pseudoaneurysm of the proximal ulnar artery. Pseudoaneurysm is a dilatation by rupture of the arterial wall, which does not involve all three layers of the arterial wall and communicates with the vascular lumen. Its development after vascular manipulation is very rare, and it is uncommon for it to act by compressing a nerve structure. In our case, together with vascular surgery, treatment with intralesional thrombin was decided, with good evolution.

Se describe el caso de un varón de 82 arios intervenido recientemente de cirugía cardíaca (cuádruple bypass coronario), que consulta por aparición de una escara necrótica en el pulpejo del dedo índice derecho, junto a parestesias e hipoestesias en los tres primeros dedos de dicha mano. Se realiza una ecografía del codo derecho para descartar afectación del nervio mediano y se objetiva una masa anecoica, de paredes engrosadas, dependientes de la pared de la arteria cubital proximal, compatible con pseudoaneurisma de esta, que comprime dicho nervio. En la electromiografía se evidencia una lesión aguda del nervio mediano a nivel proximal y en el angio-TC se confirma el diagnóstico de pseudoaneurisma de la arteria cubital proximal. El pseudoaneurisma es una dilatación por rotura de la pared arterial, que no implica a las tres capas de esta y se comunica con la luz vascular. Su desarrollo tras una manipulación vascular es muy infrecuente y que actúe comprimiendo una estructura nerviosa es poco común. En nuestro caso, conjuntamente con cirugía vascular se decidió tratamiento con trombina intralesional, con buena evolución.

Serum leptin concentration is associated with the attainment of clinical outcomes in patients with axial spondyloarthritis treated with TNF inhibitors.

OBJECTIVES: To analyse the influence of adipokines on attaining the clinical outcomes in patients with axial spondyloarthritis (axSpA) treated with TNF inhibitors (TNFi), and then, to investigate the association of patients' characteristics and adipokine concentrations. METHODS: This was a longitudinal study including 110 patients with axSpA who were initiated at TNFi and were followed-up for 6 months (m). Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline and at 6 m of treatment. Clinical outcomes at 6 m of treatment were defined as remission (ASDAS <1.3) and the attainment of low disease activity (LDA; ASDAS<2.1). Leptin and adiponectin concentrations were measured in serum samples collected at baseline and after 6 m. RESULTS: Both leptin and adiponectin were constitutively elevated in female axSpA patients. At time of TNFi initiation, leptin concentrations were higher in patients with high body mass index (overweight or obese). On the contrary, adiponectin was higher in normalweight patients. After 6 m of TNFi treatment, 24% of patients attained remission. They had significant lower leptin concentration at baseline compared with patients who did not attain remission. Furthermore, this difference remained significant after 6 m of treatment meaning that TNFi did not modify adipokine concentration. Similar results were found considering LDA as the clinical outcome, obtained in 48% of the patients. CONCLUSIONS: The present study showed that low leptin concentrations were associated with attaining clinical outcomes in axSpA patients treated with TNFi. In addition, since leptin secretion by white adipocytes is enhanced during obesity and considering that TNFi do not seem to modulate its expression, obese patients should be encouraged to decrease BMI to attain a successful therapy.

Monitoring of Circulating Tumor DNA Predicts Response to Treatment and Early Progression in Follicular Lymphoma: Results of a Prospective Pilot Study.

PURPOSE: Follicular lymphoma (FL) is the most frequent indolent non-Hodgkin lymphoma. Around 20% of patients suffer early disease progression within 24 months (POD24) of diagnosis. This study examined the significance of circulating tumor DNA (ctDNA) in predicting response to therapy and POD24 in patients with FL. EXPERIMENTAL DESIGN: We collected 100 plasma samples, before and during the treatment, from 36 patients with FL prospectively enrolled in 8 Spanish hospitals. They were treated with a chemotherapy-rituximab regimen and followed up for a median of 3.43 years. We performed targeted deep sequencing in cell-free DNA (cfDNA) and tumor genomic DNA from 31 diagnostic biopsy samples. RESULTS: Of the alterations detected in the diagnostic tissue samples, 73% (300/411) were also identified in basal cfDNA. The mean numbers of alterations per basal cfDNA sample in patients who suffered progression of disease within 24 months (POD24-pos) or did not achieve complete response (non-CR) were significantly higher than in POD24-neg or CR patients (unpaired samples t test, P = 0.0001 and 0.001, respectively). Pretreatment ctDNA levels, as haploid genome equivalents per milliliter of plasma, were higher in patients without CR (P = 0.02) and in POD24-pos patients compared with POD24-neg patients (P < 0.001). Dynamic analysis showed that ctDNA levels decreased dramatically after treatment, although the reduction was more significant in patients with CR and POD24-neg patients. CONCLUSIONS: Basal ctDNA levels are associated with the risk of early progression and response to treatment in FL. cfDNA monitoring and genotyping during treatment and follow-up predict response to treatment and early progression.

Determination of the Elution Capacity of Dalbavancin in Bone Cements: New Alternative for the Treatment of Biofilm-Related Peri-Prosthetic Joint Infections Based on an In Vitro Study.

Antibiotic-loaded bone cement is the most widely used approach for the treatment of biofilm-induced septic sequelae in orthopedic surgery. Dalbavancin is a lipoglycopeptide that acts against Gram-positive bacteria and has a long half-life, so we aimed to assess whether it could be a new alternative drug in antibiotic-loaded bone cement for the treatment of periprosthetic joint infections. We assessed the elution capacity of dalbavancin and compared it with that of vancomycin in bone cement. Palacos®R (Heraeus Medical GmbH, Wehrheim, Germany) bone cement was manually mixed with each of the antibiotics studied at 2.5% and 5%. Three cylinders were obtained from each of the mixtures; these were weighed and incubated in 5 mL phosphate-buffered saline at 37°C under shaking for 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 168 h, and 336 h. PBS was replenished at each time point. The samples were analyzed using high-performance liquid chromatography (vancomycin) and mass cytometry (dalbavancin). Elution was higher than the minimum inhibitory concentration (MIC)90 for both antibiotics after 14 days of study. The release of vancomycin at 14 days was higher than of dalbavancin at each concentration tested (p = 0.05, both). However, the cumulative release of 5% dalbavancin was similar to that of 2.5% vancomycin (p = 0.513). The elution capacity of dalbavancin reached a cumulative concentration similar to that of vancomycin. Moreover, considering that the MIC90 of dalbavancin is one third that of vancomycin (0.06 mg/L and 2 mg/L, respectively) and given the long half-life of dalbavancin, it may be a new alternative for the treatment of biofilm-related periprosthetic infections when loaded in bone cement.

Difficult-to-Treat Rheumatoid Arthritis in Older Adults: Implications of Ageing for Managing Patients.

Difficult-to-treat rheumatoid arthritis is a heterogeneous term in which patients may present with difficulties in their management for different reasons. This can ultimately lead to patients being exposed to multiple treatments because of inefficacy (resulting from mechanisms intrinsic to rheumatoid arthritis or from non-inflammatory causes such as chronic pain syndrome or structural damage, among others), toxicity or adverse effects that may be linked to comorbidities. One particular group in which such characteristics may be more patent is older patients. Increasing life expectancy, an ageing population and the late onset of rheumatoid arthritis have led to an increased interest in the particularities of treating older patients. This may pose a challenge for physicians, as ageing has implications for optimal patient treatment owing to the potential presence of comorbidities, the risk of adverse events and perceptions of disease status by both physicians and patients. All of these factors may have implications for classifying and managing patients aged > 65 years as difficult-to-treat rheumatoid arthritis, as these patients could be misclassified. This can occur when a significant proportion may still exhibit signs of active disease but not necessarily be difficult to treat because the treatment criterion has not been fulfilled. Alternatively, patients may be exposed to multiple biologic/targeted disease-modifying antirheumatic drugs because of contraindications and/or comorbid conditions. Treatment-to-target strategies and an adequate assessment of inflammatory rheumatoid arthritis activity in older patients should be undertaken, taking special care with associated comorbidities, polypharmacy and risk profiles. Such an approach can help to ensure appropriate treatment for older adults and avoid the misclassification of difficult-to-treat patients.

Tranexamic Acid in Combination With Vancomycin or Gentamicin Has a Synergistic Effect Against Staphylococci.

Background: Tranexamic acid (TXA) is an antifibrinolytic agent applied in orthopedic surgery and has been proven to reduce post-surgery infection rates. We previously showed that TXA also had an additional direct antimicrobial effect against planktonic bacteria. Therefore, we aimed to evaluate whether it has a synergistic effect if in combination with antibiotics. Materials and Methods: Three ATCC and seven clinical strains of staphylococci were tested against serial dilutions of vancomycin and gentamicin alone and in combination with TXA at 10 and 50 mg/ml. The standardized microtiter plate method was used. Minimal inhibitory concentrations (MICs) were calculated by standard visualization of well turbidity (the lowest concentration at which complete absence of well bacterial growth was observed by the researcher) and using the automated method (the lowest concentration at which ≥80% reduction in well bacterial growth was measured using a spectrophotometer). Results: Tranexamic acid-10 mg/ml reduced the MIC of vancomycin and gentamicin with both the standard method (V: 1-fold dilution, G: 4-fold dilutions) and the automated turbidity method (vancomycin: 8-fold dilutions, gentamicin: 8-fold dilutions). TXA-50 mg/ml reduced the MIC of gentamicin with both the standard turbidity method (6-fold dilutions) and the automated turbidity method (1-fold dilutions). In contrast, for vancomycin, the MIC remained the same using the standard method, and only a 1-fold dilution was reduced using the automated method. Conclusion: Ours was a proof-of-concept study in which we suggest that TXA may have a synergistic effect when combined with both vancomycin and gentamicin, especially at 10 mg/ml, which is the concentration generally used in clinical practice.

Efectiveness of belimumab in the treatment of lupus nephritis: analysis of 8 cases. / Efectividad de belimumab en el tratamiento de la nefritis lúpica: análisis de 8 casos.

INTRODUCTION AND OBJECTIVE: Belimumab is a monoclonal antibody targeting BLyS approved for Systemic Lupus Erythematosus (SLE), with recent indication for lupus nephritis (LN). To analyze effectiveness of Belimumab in LN patients. METHODS: Retrospective and cross-sectional study including SLE patients (SLICC/ACR 2012 criteria) with LN demonstrated by kidney biopsy, treated with Belimumab. A clinical history review was made and serological data, kidney function and urine sediment were collected. RESULTS: Eight patients with LN demonstrated by kidney biopsy were included. Median age was 37.56 (7.03) years, with 15.13 (8.71) years since SLE diagnosis was made and 4.61 (2.64) years since onset of belimumab. Proteinuria was reduced to normal values in 6 patients, and renal function was stable from the beginning of treatment in all cases. There was a reduction in the anti-DNA level and normalization of complement in those cases in which it was reduced. One patient presented an increase in anti-DNA titer, with normal complement. CONCLUSIONS: In clinical practice, belimumab can improve LN in terms of serological activity, kidney function and urine sediment.

Lenalidomide plus R-GDP (R2-GDP) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Final Results of the R2-GDP-GOTEL Trial and Immune Biomarker Subanalysis.

PURPOSE: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. PATIENTS AND METHODS: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). RESULTS: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. CONCLUSIONS: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.

Antibody Response Induced by BNT162b2 and mRNA-1273 Vaccines against the SARS-CoV-2 in a Cohort of Healthcare Workers.

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.

Study of Plasma Anti-CD26 Autoantibody Levels in a Cohort of Treatment-Naïve Early Arthritis Patients.

In rheumatoid arthritis (RA), the identification of biomarkers to adjust treatment intensity and to correctly diagnose the disease in early stages still constitutes a challenge and, as such, novel biomarkers are needed. We proposed that autoantibodies (aAbs) against CD26 (DPP4) might have both etiological importance and clinical value. Here, we perform a prospective study of the potential diagnostic power of Anti-CD26 aAbs through their quantification in plasmas from 106 treatment-naïve early and undifferentiated AR. Clinical antibodies, Anti-CD26 aAbs, and other disease-related biomarkers were measured in plasmas obtained in the first visit from patients, which were later classified as RA and non-RA according to the American College of Rheumatology criteria. Two different isotype signatures were found among ten groups of patients, one for Anti-CD26 IgA and other for Anti-CD26 IgG and IgM isotypes, both converging in patients with arthritis (RA and Unresolved Undifferentiated Arthritis: UUA), who present elevated levels of all three isotypes. The four UUA patients, unresolved after two years, were ACPA and rheumatic factor (RF) negatives. In the whole cohort, 51.3% of ACPA/RF seronegatives were Anti-CD26 positives, and a similar frequency was observed in the seropositive RA patients. Only weak associations of the three isotypes with ESR, CRP and disease activity parameters were observed. Anti-CD26 aAbs are present in treatment-naïve early arthritis patients, including ACPA and RF seronegative individuals, suggestive of a potential pathogenic and/or biomarker role of Anti-CD26 aAbs in the development of rheumatic diseases.

Primary Sjögren's syndrome as independent risk factor for subclinical atherosclerosis.

OBJECTIVE: To assess the prevalence of subclinical atherosclerosis in patients with primary Sjögren's syndrome (pSS) and its possible association with clinical and analytical parameters of the disease. METHODS: In this cross-sectional study, 38 consecutive patients with pSS were compared with 38 age and sex healthy controls. Demographic variables and classic cardiovascular risk factors (CVRFs): Hypertension, dyslipidemia, diabetes mellitus, obesity, and smoking habit were assessed in both groups, and also disease-related features were collected in pSS group. The presence of subclinical atherosclerosis was assessed by carotid ultrasound, with carotid intima-media thickness (CIMT) measurement and determination of the presence of atheromatous plaques. RESULTS: Subclinical atherosclerosis presence was remarkably greater in patients with pSS than in healthy controls (OR = 4.17, 95%CI [1.27-16.54]), as well as CIMT values (0.79 ± 0.43mm vs. 0.66 ± 0.27mm; P = .02). No differences for classic CVRFs were found between both groups. An association of subclinical atherosclerosis with erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF) was observed in patients with pSS. CONCLUSION: This cohort showed a greater prevalence of subclinical atherosclerosis in patients with pSS, indicating this disease as an independent risk factor for presence of early vascular damage.

Radiological evolution of autograft fat used for skull base reconstruction after transsphenoidal surgery for pituitary adenomas.

PURPOSE: Cerebro-spinal fluid leak after transsphenoidal surgery for pituitary adenomas may be prevented by skull base reconstruction with fat autograft. However, graft changes may interfere with the interpretation of postoperative images. Our aim is to describe the radiological evolution of the fat autograft. METHODS: A retrospective analysis was performed, including patients undergoing a transsphenoidal surgery for pituitary adenomas with a fat autograft for skull base reconstruction. Clinical and radiological data were collected, with assessment of fat autograft and extent of resection. Statistical analysis was performed using Kruskal-Wallis and Wilcoxon signed-rank test while Spearman's Rho was used to analyze the relationship between variables. RESULTS: Seventy-two patients were included. Macroadenomas were diagnosed in 62 cases (86.1%) and in 21 cases an invasion of the cavernous sinus was described (29%). Gross total resection was achieved in 84.7% of cases. The volume of the fat graft significantly decreased between 3 months and 1 year after surgery (p = 0.01) and between 1 year and the last follow-up (mean 4.63 years, p < 0.01). Fat signal ratio significantly diminished between 3 months and 1 year in unenhanced and enhanced T1-weighted sequences (p = 0.04 and p = 0.02 respectively). Volume reduction was related to the decrease in signal ratio in unenhanced T1 sequences (p = 0.008). CONCLUSION: Fat resorbs with time: almost 50% of the fat volume is lost during the first year after surgery and 60% is resorbed at 4.6 years. T1-signal, before and after gadolinium injection, also decreases during the first year, probably because of the progressive fibrosis of the graft. This information will contribute to the interpretation of postoperative images.

Effect of Tranexamic Acid against Staphylococcus spp. and Cutibacterium acnes Associated with Peri-Implant Infection: Results from an In Vitro Study.

Tranexamic acid (TXA) is extensively used in orthopedic surgery and traumatology as an antifibrinolytic agent to control intra- and postoperative bleeding and, therefore, indirectly, to reduce postsurgery infection rates. The hypothesis of an additional antibiotic effect against microorganisms associated with periprosthetic joint infection needs to be further evaluated. We aimed to assess whether TXA could reduce bacterial growth using an in vitro model. ATCC and clinical strains of staphylococci and Cutibacterium acnes were tested against TXA in both planktonic and sessile forms. We recorded the percent reduction in the following variables: log CFU/mL by microbiological culture, percentage of live cells by confocal laser scanning microscopy, and, additionally in sessile cells, metabolic activity by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) assay. Variables were compared between groups using the Kruskal-Wallis test, and the results were reported as median (interquartile range [IQR]). Statistical significance was set at a P value of <0.05. Clinical significance was defined as a reduction of ≥25%. TXA at 50 mg/mL led to a slight reduction in CFU counts (4.5%). However, it was at 10 mg/mL that the reduction reached 27.2% and 33.0% for log CFU/mL counts and percentage of live cells, respectively. TXA was not efficacious for reducing preformed 24-h mature staphylococci and 48-h mature C. acnes biofilms, regardless of its concentration. TXA did not exert an antimicrobial effect against bacterial biofilms. However, when bacteria were in the planktonic form, it led to a clinically and statistically significant reduction in bacterial growth at 10 mg/mL. IMPORTANCE The possible use of TXA as an antibiotic agent in addition to its antifibrinolytic effect may play an important role in the prevention of prosthetic joint infection.

Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass index and adipose tissue cytokines.

OBJECTIVES: To analyse the role of body mass index (BMI) in the clinical response to biologic dis-ease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). To per-form an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment. METHODS: This study involved 105 patients with RA starting tumour necrosis factor inhibitors (TNFi) or tocilizumab (TCZ). Patients were classified ac-cording to BMI as normal-weight and overweight/obesity. The clinical response to treatment was as-sessed by Clinical Disease Activity Index (CDAI) 6 months after initiation of bDMARDs. Serum adi-pokines (leptin and adiponectin) were determined using a commercial immunoassay kit in samples ob-tained before initiation of bDMARDs and after 6 months of treatment. RESULTS: A correlation was observed between BMI and disease activity and between BMI and serum adipokines. Sixty percent of patients achieved low disease activity (LDA)/remission: 45 patients in TNFi group (64.2%) and 18 (51.4%) in TCZ group. In TNFi group, patients who did not attain LDA/remission had a higher BMI (kg/m2) ([28.7±5.1] vs. [24.5±4.6], p=0.001) and baseline CDAI (26.3 [17.4-33.9] vs. 19.8 [14.0-28.8], p<0.03). However, no differences in BMI or baseline CDAI were observed between patients who achieved LDA after 6 months in TCZ group. CONCLUSIONS: Obesity influences the extent of LDA/remission in patients treated with TNFi, but not in patients treated with TCZ, probably because of underlying pathophysiological mechanisms intrinsic to the production of proinflammatory adi-pokines. Therefore, therapeutic strategies with a mechanism of action other than TNF inhibition would be more suitable for obese patients.

Bronchoalveolar Lavage Complements Transbronchial Cryobiopsy Diagnosis in Diffuse Interstitial Lung Diseases.

BACKGROUND: Bronchoalveolar lavage (BAL) is a technique classically used for the study of diffuse interstitial lung diseases (DILDs). Given the recent advances in the diagnosis of DILD by transbronchial cryobiopsy (TBCB), it is relevant to assess what BAL can contribute to TBCB. PATIENTS AND METHODS: This is a retrospective descriptive study that included patients with DILD who, between 2013 and 2017, underwent BAL and TBCB in the same bronchoscopy intervention. We evaluated the complementary information provided by BAL to TBCB that facilitated the diagnosis by a multidisciplinary committee. Epidemiological, clinical, and functional variables and high-resolution chest tomography findings were recorded, along with complications associated with the procedures. RESULTS: A total of 60 patients were included. TBCB, conditioned by the underlying radiologic pattern, provided diagnostic information in 75% of cases. BAL provided complementary information that supported the diagnosis and treatment in 22% of cases. Differential BAL findings were related to microbiology, cell count, and immunology. Regarding the safety of the procedure, 47% of the patients experienced complications, although none were serious. CONCLUSION: BAL findings contribute to TBCB findings in the diagnosis of DILDs, with no serious complications associated with their combined use.