Clinical Characteristics and Microorganisms Isolated in Community-Acquired Pneumonia in the COVID-19 Period.

Introduction: Community-acquired pneumonia is a leading cause of mortality and hospital admissions. The aetiology remains unknown in 30-65% of the cases. Molecular tests are available for multiple pathogen detection and are under research to improve the causal diagnosis. Methods: We carried out a prospective study to describe the clinical characteristics and aetiology of community-acquired pneumonia during the COVID-19 pandemic and to assess the diagnostic effectivity of the microbiological tests, including a molecular test of respiratory pathogens (FilmArray™ bioMérieux). Results: From the 1st of February 2021 until the 31st of March 2022, 225 patients were included. Failure in microorganism identification occurred in approximately 70% of patients. Streptococcus pneumoniae was the most common isolate. There were 5 cases of viral pneumonia. The tested FilmArray exhibited a low positivity rate of 7% and mainly aided in the diagnosis of viral coinfections. Conclusions: Despite our extensive diagnostic protocol, there is still a low rate of microorganism identification. We have observed a reduction in influenza and other viral pneumoniae during the COVID-19 pandemic. Having a high NEWS2 score on arrival at the emergency department, an active oncohematological disease or chronic neurological conditions and a positive microbiological test result were related to worse outcomes. Further research is needed to determine the role of molecular tests in the microbiological diagnosis of pneumonia.

Analysis of vaccine responses after anti-CD20 maintenance in B-cell lymphoma in the Balearic Islands. A single reference center experience.

Introduction: The use of maintenance approaches with anti-CD20 monoclonal antibodies has improved the outcomes of B-cell indolent lymphomas but may lead to significant peripheral B-cell depletion. This depletion can potentially hinder the serological response to neoantigens. Methods: Our objective was to analyze the effect of anti-CD20 maintenance therapy in a reliable model of response to neoantigens: SARS-CoV-2 vaccine responses and the incidence/severity ofCOVID-19 in a reference hospital. Results: In our series (n=118), the rate of vaccination failures was 31%. Through ROC curve analysis, we determined a cutoff for SARS-CoV-2 vaccine serologic response at 24 months from the last anti-CD20 dose. The risk of severe COVID-19 was notably higher within the first 24months following the last anti-CD20 dose (52%) compared to after this period (just 18%) (p=0.007). In our survival analysis, neither vaccine response nor hypogammaglobulinemia significantly affected OS. While COVID-19 led to a modest mortality rate of 2.5%, this figure was comparable to the OS reported in the general immunocompetent population. However, most patients with hypogammaglobulinemia received intravenous immunoglobulin therapy and all were vaccinated. In conclusion, anti-CD20 maintenance therapy impairs serological responses to SARS-CoV-2 vaccines. Discussion: We report for the first time that patients during maintenance therapy and up to 24 months after the last anti-CD20 dose are at a higher risk of vaccine failure and more severe cases of COVID-19. Nevertheless, with close monitoring, intravenous immunoglobulin supplementation or proper vaccination, the impact on survival due to the lack of serological response in this high-risk population can be mitigated, allowing for the benefits of anti-CD20 maintenance therapy, even in the presence of hypogammaglobulinemia.

Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island.

The hyperinflammatory response caused by SARS-CoV-2 infection contributes to its severity, and many critically ill patients show features of cytokine storm (CS) syndrome. We investigated, by next-generation sequencing, 24 causative genes of primary immunodeficiencies whose defect predisposes to CS. We studied two cohorts with extreme phenotypes of SARS-CoV-2 infection: critical/severe hyperinflammatory patients (H-P) and asymptomatic patients (AM-risk-P) with a high risk (older age) to severe COVID-19. To explore inborn errors of the immunity, we investigated the presence of pathogenic or rare variants, and to identify COVID-19 severity-associated markers, we compared the allele frequencies of common genetic polymorphisms between our two cohorts. We found: 1 H-P carries the likely pathogenic variant c.887-2 A>C in the IRF7 gene and 5 H-P carries variants in the MEFV gene, whose role in the pathogenicity of the familial Mediterranean fever (FMF) disease is controversial. The common polymorphism analysis showed three potential risk biomarkers for developing the hyperinflammatory response: the homozygous haplotype rs1231123A/A-rs1231122A/A in MEFV gene, the IFNAR2 p.Phe8Ser variant, and the CARMIL2 p.Val181Met variant. The combined analysis showed an increased risk of developing severe COVID-19 in patients that had at least one of our genetic risk markers (odds ratio (OR) = 6.2 (95% CI) (2.430-16.20)).

Reversions of QuantiFERON-TB Gold Plus in tuberculosis contact investigation: A prospective multicentre cohort study.

BACKGROUND: Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. METHODS: Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive. RESULTS: We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes. CONCLUSION: In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments.

Elevated complement C3 and increased CD8 and type 1 helper lymphocyte T populations in patients with post-COVID-19 condition.

BACKGROUND: Biological markers associated to post-COVID-19 condition (PCC) have not been clearly identified. METHODS: Eighty-two patients attending our post-COVID-19 outpatient clinic were recruited and classified as fully recovered (40.2%) or presenting with PCC (59.8%). Clinical and radiological data, laboratory markers, cytokines, and lymphocyte populations were analyzed. RESULTS: Median number of days after hospitalization was 78.5 [p25-p75: 60-93] days. PCC was significantly more frequent in women, in patients with a previously critical COVID-19, and in those with two or more comorbidities. No differences were found in lymphocyte counts, ferritin, C-reactive protein, D-dimer or sCD25, IL-1ß, IL-1Ra, IL-6, CXCL8, IL-17A, IL-18, IL-22, IFN-γ, TNF-α, and IL-10 cytokines levels. PCC patients showed significantly higher levels of complement factor C3 than fully recovered patients: median C3 128 mg/dL [p25-p75:107-135] vs 111 mg/dL [p25-p75: 100-125] (p =.005), respectively. In the flow cytometry assessment of peripheral blood lymphocyte subpopulations, PCC patients showed significantly increased CD8 populations compared to fully recovered patients: median CD8: 529 [p25-p75: 384-683] vs 370/mm3 [p25-p75:280-523], p =.007. When type 1, 2, 17/22, and 17.1 helper and follicular T lymphocyte subpopulations were analyzed, the frequency of Th1 was significantly higher in PCC patients compared to fully recovered patients (30% vs 38.5%, p =.028). CONCLUSION: Patients with a post-COVID-19 condition showed significantly increased immunological parameters of inflammation (complement factor C3 and CD8 and Th1 T lymphocyte populations) compared to fully recovered patients. These parameters could be used as biological markers of this condition.

Sclerosing mesenteritis due to Mycobacterium genavense infection: A case report.

RATIONALE: Since its first identification in the early 1990s, Mycobacterium genavense has been considered and opportunistic pathogen. It mainly causes gastrointestinal symptoms, but also disseminated infections in severely immunosuppressed patients. Sclerosing mesenteritis is a long-term complication with high morbidity and mortality. As it is a rare condition, there are no specific guidelines for its management. We report a challenging case of persistent M. genavense infection, and propose surgery as an alternative treatment strategy. PATIENT CONCERNS: A 38-year-old Caucasian man presented to the emergency room with fever, abdominal pain, and night sweats for 3 months. HIV screening revealed a previously unknown HIV-1 infection, with a CD4 cell count of 216 cell/µL and viral load of 361.000 copies/mL at diagnosis. A body CT-scan showed mild splenomegaly as well as mesenteric and retroperitoneal enlarged lymph nodes. Fine needle aspiration revealed the presence of acid-fast bacilli, but mycobacterial cultures were negative. In the second sample, 16S RNA sequencing yielded a diagnosis of M. genavense infection. Despite 2 years of corticosteroids and antimycobacterial treatment excluding rifampicin due to a severe cutaneous reaction, there was no clinical improvement and an increase in the mesenteric lymph node size was observed, with a sclerosing transformation of the mesentery. A surgical approach was proposed to release small bowel loops and to remove fibrin. A second surgery was required due to an acute peritonitis ought to yeyunal segmental isquemia and perforation. Finally, the patient evolved favorably, and antimycobacterial drugs were suspended without relapse. LESSONS: Despite a prolonged multidrug strategy, some patients develop persistent M. genavense infection. Once sclerosing mesenteritis is established, clinicians have few treatment options. Surgery should be considered in patients with sclerosing mesenteritis or bowel obstruction. The combination of medical and surgical treatment could be a potential cure for these patients.

Increased mRNA Levels of ADAM17, IFITM3, and IFNE in Peripheral Blood Cells Are Present in Patients with Obesity and May Predict Severe COVID-19 Evolution.

Gene expression patterns in blood cells from SARS-CoV-2 infected individuals with different clinical phenotypes and body mass index (BMI) could help to identify possible early prognosis factors for COVID-19. We recruited patients with COVID-19 admitted in Hospital Universitari Son Espases (HUSE) between March 2020 and November 2021, and control subjects. Peripheral blood cells (PBCs) and plasma samples were obtained on hospital admission. Gene expression of candidate transcriptomic biomarkers in PBCs were compared based on the patients' clinical status (mild, severe and critical) and BMI range (normal weight, overweight, and obesity). mRNA levels of ADAM17, IFITM3, IL6, CXCL10, CXCL11, IFNG and TYK2 were increased in PBCs of COVID-19 patients (n = 73) compared with controls (n = 47), independently of sex. Increased expression of IFNE was observed in the male patients only. PBC mRNA levels of ADAM17, IFITM3, CXCL11, and CCR2 were higher in those patients that experienced a more serious evolution during hospitalization. ADAM17, IFITM3, IL6 and IFNE were more highly expressed in PBCs of patients with obesity. Interestingly, the expression pattern of ADAM17, IFITM3 and IFNE in PBCs was related to both the severity of COVID-19 evolution and obesity status, especially in the male patients. In conclusion, gene expression in PBCs can be useful for the prognosis of COVID-19 evolution.

Hyperinflammatory State and Low T1 Adaptive Immune Response in Severe and Critical Acute COVID-19 Patients.

Background: A better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options. Objective: We aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19. Methods: 139 hospitalized patients with COVID-19-58 mild/moderate and 81 severe/critical-and 74 recovered patients were included in a prospective longitudinal study. Clinical data and blood samples were obtained on admission for laboratory markers, cytokines, and lymphocyte subsets study. In the recovered patients, lymphocyte subsets were analyzed 8-12 weeks after discharge. Results: A National Early Warning Score 2 >2 (OR:41.4; CI:10.38-167.0), ferritin >583 pg/mL (OR:16.3; CI: 3.88-69.9), neutrophil/lymphocyte ratio >3 (OR: 3.5; CI: 1.08-12.0), sIL-2rα (sCD25) >512 pg/mL (OR: 3.3; CI: 1.48-7.9), IL-1Ra >94 pg/mL (OR: 3.2; IC: 1.4-7.3), and IL-18 >125 pg/mL (OR: 2.4; CI: 1.1-5.0) were associated with severe/critical COVID-19 in the multivariate models used. Lower absolute values of CD3, CD4, CD8, and CD19 lymphocytes together with higher frequencies of NK cells, a CD4 and CD8 activated (CD38+HLA-DR+) memory T cell and effector memory CD45RA+ (EMRA) phenotype, and lower T regulatory cell frequencies were found in severe/critical patients relative to mild/moderate and recovered COVID-19 patients. A significant reduction in Th1, Tfh1, and Tc1 with higher Th2, Tfh2, Tc2, and plasma cell frequencies was found in the most severe cases. Conclusion: A characteristic hyperinflammatory state with significantly elevated neutrophil/lymphocyte ratio and ferritin, IL-1Ra, sIL-2rα, and IL-18 levels together with a "low T1 lymphocyte signature" was found in severe/critical COVID-19 patients.

Identification of Recent Tuberculosis Exposure Using QuantiFERON-TB Gold Plus, a Multicenter Study.

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2-TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8+ T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value >0.6 IU·ml-1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU·ml-1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of >0.6 IU·ml-1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml-1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml-1. QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.

Efficacy and Safety of Sarilumab in patients with COVID19 Pneumonia: A Randomized, Phase III Clinical Trial (SARTRE Study).

INTRODUCTION: SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS). METHODS: We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15. RESULTS: A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48-2.20). No relevant safety issues were identified. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.

Predictive Immunological, Virological, and Routine Laboratory Markers for Critical COVID-19 on Admission.

BACKGROUND: Early identification of COVID-19 patients at risk of critical illness is a challenging endeavor for clinicians. We aimed to establish immunological, virological, and routine laboratory markers, which, in combination with clinical information, may allow identifying such patients. METHODS: Blood tests to measure neutrophil/lymphocyte ratio (NLR) and levels of ferritin, CRP, D-dimer, complement components (C3 and C4), cytokines, and lymphocyte subsets, as well as SARS-Cov-2 RT-PCR tests, were performed in COVID-19-confirmed cases within 48 hours of admission. RT-PCR cycle threshold (Ct) values from oropharyngeal or nasopharyngeal swabs were determined on the day of admission. Symptom severity was categorized as mild (grade 1), severe (grade 2), or critical (grade 3). RESULTS: Of 120 patients who were included, 49 had mild, 32 severe, and 39 critical COVID-19. Levels of ferritin >370 ng/mL (OR 16.4, 95% CI 5.3-50.8), D-dimer >440 ng/mL (OR 5.45, 95% CI 2.36-12.61), CRP >7.65 mg/dL (OR 11.54, 95% CI 4.3-30.8), NLR >3.77 (OR 13.4, 95% CI 4.3-41.1), IL-6 >142.5 pg/mL (OR 8.76, 95% CI 3.56-21.54), IL-10 >10.8 pg/mL (OR 16.45, 95% CI 5.32-50.81), sIL-2rα (sCD25) >804.5 pg/mL (OR 14.06, 95% CI 4.56-43.28), IL-1Ra >88.4 pg/mL (OR 4.54, 95% CI 2.03-10.17), and IL-18 >144 pg/mL (OR 17.85, 95% CI 6.54-48.78) were associated with critical COVID-19 in the univariate age-adjusted analysis. This association was confirmed in the multivariate age-adjusted analysis only for ferritin, CRP, NLR, IL-10, sIL-2rα, and IL-18. T, B, and NK cells were significantly decreased in critical patients. SARS-CoV-2 was not detected in blood except in 3 patients who had indeterminate results. RT-PCR Ct values from oropharyngeal or nasopharyngeal swabs on admission were not related to symptom severity. CONCLUSION: Ferritin, D-dimer, CRP, NLR, cytokine (IL-18 and IL-10), and cytokine receptor (IL-6, IL1-Ra, and sCD25) test results combined with clinical data can contribute to the early identification of critical COVID-19 patients.

Use of Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry Analysis of Serum Peptidome to Classify and Predict Coronavirus Disease 2019 Severity.

BACKGROUND: Classification and early detection of severe coronavirus disease 2019 (COVID-19) patients is required to establish an effective treatment. We tested the utility of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to classify and predict the severity of COVID-19. METHODS: We used MALDI-TOF MS to analyze the serum peptidome from 72 patients with COVID-19 (training cohort), clinically classified as mild (28), severe (23), and critical (21), and 20 healthy controls. The resulting matrix of peak intensities was used for Machine Learning (ML) approaches to classify and predict COVID-19 severity of 22 independent patients (validation cohort). Finally, we analyzed all sera by liquid chromatography mass spectrometry (LC-MS/MS) to identify the most relevant proteins associated with disease severity. RESULTS: We found a clear variability of the serum peptidome profile depending on COVID-19 severity. Forty-two peaks exhibited a log fold change ≥1 and 17 were significantly different and at least 4-fold more intense in the set of critical patients than in the mild ones. The ML approach classified clinical stable patients according to their severity with 100% accuracy and correctly predicted the evolution of the nonstable patients in all cases. The LC-MS/MS identified 5 proteins that were significantly upregulated in the critical patients. They included the serum amyloid protein A2, which probably yielded the most intense peak detected by MALDI-TOF MS. CONCLUSIONS: We demonstrate the potential of the MALDI-TOF MS as a bench to bedside technology to aid clinicians in their decision making regarding patients with COVID-19.

Paper biosensors for detecting elevated IL-6 levels in blood and respiratory samples from COVID-19 patients.

Decentralizing COVID-19 care reduces contagions and affords a better use of hospital resources. We introduce biosensors aimed at detecting severe cases of COVID-19 in decentralized healthcare settings. They consist of a paper immunosensor interfaced with a smartphone. The immunosensors have been designed to generate intense colorimetric signals when the sample contains ultralow concentrations of IL-6, which has been proposed as a prognosis biomarker of COVID-19. This is achieved by combining a paper-based signal amplification mechanism with polymer-filled reservoirs for dispensing antibody-decorated nanoparticles and a bespoken app for color quantification. With this design we achieved a low limit of detection (LOD) of 10-3 pg mL-1 and semi-quantitative measurements in a wide dynamic range between 10-3 and 102 pg mL-1 in PBS. The assay time is under 10 min. The low LOD allowed us to dilute blood samples and detect IL-6 with an LOD of 1.3 pg mL-1 and a dynamic range up to 102 pg mL-1. Following this protocol, we were able to stratify COVID-19 patients according to different blood levels of IL-6. We also report on the detection of IL-6 in respiratory samples (bronchial aspirate, BAS) from COVID-19 patients. The test could be easily adapted to detect other cytokines such as TNF-α and IL-8 by changing the antibodies decorating the nanoparticles accordingly. The ability of detecting cytokines in blood and respiratory samples paves the way for monitoring local inflammation in the lungs as well as systemic inflammation levels in the body.

Facial Nerve Palsy as a Neurological Manifestation of COVID-19.

Facial nerve palsy is the most frequent acute mononeuropathy and it is often of viral etiology, although many other causes have been identified. It has recently been described as a potential manifestation of COVID-19. We report the case of a patient with recent history of diarrhea and malaise that was admitted to the hospital presenting right facial paresis with orbicular muscle involvement. Nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the real-time reverse transcription polymerase chain reaction and magnetic resonance imaging showed no structural changes. During the hospital stay, the patient showed clinical improvement, and no other symptoms were observed. This case presentation suggests a possible association between neuropathies and SARS-CoV-2 infection.

Efficacy and Freedom: Patient Experiences with the Transition from Daily Oral to Long-Acting Injectable Antiretroviral Therapy to Treat HIV in the Context of Phase 3 Trials.

Long-acting injectable antiretroviral therapy (LA ART) may be an alternative for people living with HIV (PLHIV) with adherence challenges or who prefer not to take pills. Using in-depth interviews, this study sought to understand the experiences of PLHIV (n = 53) participating in Phase 3 LA ART trials in the United States and Spain. The most salient consideration when contemplating LA ART was its clinical efficacy; many participants reported wanting to ensure that it worked as well as daily oral ART, including with less frequent dosing (every 8 versus 4 weeks). While injection side effects were often reported, most participants felt that regimen benefits outweighed such drawbacks. Participants described the main benefit of LA ART as the "freedom" it afforded both logistically and psychosocially, including through reduced HIV stigma. Findings highlight the importance of patient-provider communication related to weighing potential benefits and side effects and the continued need to address HIV stigma.

Polyserositis: a diagnostic challenge.

BACKGROUND: Polyserositis (PS) is the inflammation, with effusion, of different serous membranes. It has been associated with different aetiologies, but the aetiology of PS remains unknown in a high percentage of patients. AIMS: The general objective of this retrospective study was to analyse the aetiology of PS cases seen at Son Llàtzer Hospital in an 11-year period. Other objectives were to determine the epidemiological, clinical and analytical characteristics of these patients. METHODS: An observational, descriptive and retrospective study to analyse the aetiology of PS cases seen at Son Llàtzer Hospital. The inflammation of two or more serous membranes confirmed by an imaging test was required and at least one of the serous fluid should be an exudate. RESULTS: A total of 92 patients was included in the study. The most common diagnosis was neoplasm (nearly one-third of cases) followed by infectious and autoimmune diseases. PS aetiology was unknown in more than one-third. Pleura and pericardium were the most common sites of serosal involvement (83%). Antinuclear antibodies' positivity in serum and increased levels of adenosine deaminase in pleural effusion were significantly associated with a final diagnosis of autoimmune disease. Increased pleural lactate dehydrogenase levels were significantly associated with a final diagnosis of neoplasm. In 9 of 14 patients with a previous cancer, PS represented a recurrence of their cancer. Cases of unknown aetiology presented most frequently as pleural and pericardial involvement, and the majority resolved. In very few patients, an infectious aetiology could be proven. CONCLUSION: PS is a frequent clinical entity that is associated with different diseases and its diagnosis could be challenging, with a high rate of unknown aetiologies.

QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.

Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.

IGRA testing in patients with immune-mediated inflammatory diseases: which factors influence the results?

Diagnosis of latent tuberculosis infection in patients with immune-mediated inflammatory chronic diseases (IMIDs) can be challenged as diagnostic test reliability could be impaired by immunosuppression. We retrospectively analyzed the Quantiferon Gold-Test in-Tube (QFT-G-IT) results of all patients with IMIDs seen at the Department of Internal Medicine of Son Llàtzer Hospital, Palma de Mallorca (Spain), looking for the factors related to QFT-G-IT indeterminate results. During the study period (2008-2015), 520 patients met the inclusion criteria. Factors associated with indeterminate QFT-G-IT results in a univariate analysis were inflammatory bowel disease, disease activity, lymphopenia, and medium-to-high doses of corticosteroids. In a subsequent multivariate analysis, only lymphopenia (defined as < 1500 cells) was associated with indeterminate QFT-G-IT results. Lymphocyte count was the only factor independently associated with an increased number of indeterminate QFT-G-IT results in patients with different autoimmune diseases. Others factors such as the use of medium-to-high doses of corticosteroids should be considered before testing with QFT-G-IT.

Sumario ejecutivo de la guía de práctica clínica sobre el uso de las pruebas de liberación de interferón-gamma para el diagnóstico de infección tuberculosa / Executive Summary of the Guidelines for the Use of interferon-gamma Release Assays in the Diagnosis of Tuberculosis Infection

El uso de las pruebas de liberación de interferón-gamma para el diagnóstico de la infección tuberculosa está muy generalizado en España. Sin embargo, no se ha alcanzado un consenso respecto a su aplicación en situaciones clínicas específicas. Con el fin de redactar una guía de empleo en la práctica clínica, un grupo de expertos que incluyó a especialistas en enfermedades infecciosas, enfermedades respiratorias, microbiología, pediatría y medicina preventiva, junto con un experto en metodología, efectuaron una búsqueda sistemática en la literatura, sintetizaron los resultados, calificaron la calidad de las evidencias y formularon recomendaciones de acuerdo con la metodología Grading of Recommendations of Assessment Development and Evaluations. Este documento es una guía basada en la evidencia para el empleo de las pruebas de liberación de interferón-gamma en el diagnóstico de la infección tuberculosa en pacientes en riesgo de padecer tuberculosis o en los que se sospeche enfermedad activa. La guía será aplicable tanto en atención primaria y especializada como en salud pública

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guide-line for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the Grading of Recommendations of Assessment Development and Evaluations methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health