Survival and Lung Function Changes in Hypersensitivity Pneumonitis According to Radiological Phenotypes Compared With Idiopathic Pulmonary Fibrosis.

INTRODUCTION: The main objective of this study was to estimate survival and changes in lung function in patients with chronic hypersensitivity pneumonitis (HP), both fibrotic (f-HP) and nonfibrotic (nf-HP), and to compare them with those in patients with idiopathic pulmonary fibrosis (IPF). METHODS: HP was diagnosed based on antigen exposure, HRCT (high-resolution CT scan), BAL (bronchoalveolar lavage), and histology. According to HRCT, HP was classified into fibrotic and non-fibrotic phenotypes. In most cases, IPF was diagnosed based on HRCT findings. RESULTS: We identified 84 patients: 46 with IPF, 18 with f-HP, and 20 with nf-HP. Five-year survival was 23.9% in IPF, 72% in f-HP, and 100% in nf-HP (p <0.0001). Honeycombing was associated with decreased survival in IPF (p <0.001) and in f-HP (p <0.0001). The mean loss of FVC (forced vital capacity) % pred. (percent predicted) was -18.3% in IPF (p =0.001), -4.8% in f-HP, and -6.0% in nf-HP. The mean change in DLCO (diffusion capacity for carbon monoxide) % pred. was -10.2% in IPF (p <0.002), -0.5% in f-HP, and +1.9% in nf-HP. The agreement between radiological phenotypes and histology in HP was 89.6%. CONCLUSIONS: We found shorter survival in IPF, followed by f-HP, and nf-HP. Over time, we did not find significant changes in FVC% pred. or DLCO% pred. in HP, while a significant decline in IPF was noted. In HP, we found strong agreement between radiological phenotypes and histology. Radiological signs suggestive of lung fibrosis in HP were reliable for the diagnosis of f-HP and seem to have intrinsic prognostic value.

[Human resources in the National Health System. Medical education. SESPAS Report 2024]. / Recursos humanos del Sistema Nacional de Salud. Formación. Informe SESPAS 2024.

The problems posed by medical education in Spain are diverse. This paper analyzes the system currently used to select candidates who will be admitted to a public faculty of medicine in Spain and some issues arising from the unprecedented increase in both public and private medical schools in our country. The importance of generic competencies in today's medicine and the need to return to a core design in specialist training are other aspects that are discussed. The degree of development of advanced accreditation diplomas and areas of specific competence is also subject to analysis. Finally, the authors emphasize the importance of continuous professional development and the idea of professional recertification as a system that guarantees patients the quality of the care they receive.

Prevalence of Oropharyngeal Dysphagia and Its Value as a Prognostic Factor in Community-Acquired Pneumonia: A Prospective Case-Control Study.

BACKGROUND: Although oropharyngeal dysphagia (OD) is a common finding in patients with community-acquired pneumonia (CAP), specific recommendations are not provided in the current clinical guidelines. OBJECTIVES: To estimate the prevalence of OD and its associated factors among patients hospitalized for CAP and to assess one-year outcomes according to the presence or absence of OD. METHODS: We studied 226 patients hospitalized for CAP and 226 patients hospitalized for respiratory conditions other than CAP. We screened the risk of OD using the Eating Assessment Tool-10 (EAT-10), followed by the volume-viscosity swallow test (V-VST). RESULTS: A total of 122 (53.9%) patients with CAP had confirmed OD compared with 44 (19.4%) patients without CAP. Patients with CAP and OD were older (p < 0.001; 1.02-1.07) and had less familial/institutional support (p = 0.036; 0.12-0.91) compared to patients with CAP and no OD. OD was more prevalent as the CURB-65 score increased (p < 0.001). Patients with OD spent more time in the hospital (14.5 vs. 11.0 days; p = 0.038) and required more visits to the emergency room (ER). Twenty (16.4%) patients with CAP and OD died after discharge vs. one (0.8%) patient with CAP and no OD (p < 0.001; CI = 2.24-42.60). CONCLUSIONS: The prevalence of OD in hospitalized patients with CAP is higher than in patients hospitalized for other respiratory diagnoses. Advanced age, lower familial/institutional support, and increased CAP severity are associated with OD. Patients with CAP and OD are more frequent ER visitors after discharge and have a higher mortality. In patients with CAP and OD, aspiration pneumonia is likely underestimated.

Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.

Autoantibodies against type I IFNs in patients with critical influenza pneumonia.

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.

Challenges in understanding host genetics and severity of community-acquired pneumonia.

This study found no association of the top two associated FER variants with severity of community-acquired pneumonia. Precise characterisation of phenotypes may be required in order to unravel the genetic mechanisms predisposing to poor outcome in sepsis. https://bit.ly/3jc9SmR.

Multi-drug resistant tuberculosis, ten years later. / Tuberculosis multirresistentediez años después.

Drug-resistant tuberculosis, especially those with resistance to rifampicin (RR-TB), has become one of the main obstacles to achieving the dream of eradicating tuberculosis. Furthermore, it is necessary to combine three or four different drugs in the attempt to cure TB, however, unfortunately, there are few available that can be considered genuinely effective. Fortunately, the notable worldwide increase in RR-TB in recent years has led to the investment of resources in the development of new drugs for TB, and other drugs investigated for other diseases have been successfully tested on TB. This has resulted in a clear change in the clinical management of these patients over the last 3-4 years, and it is now easier to design therapeutic regimens and achieve higher success rates. All these changes are updated in this review.

Should MASP-2 Deficiency Be Considered a Primary Immunodeficiency? Relevance of the Lectin Pathway.

Mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) is an indispensable enzyme for the activation of the lectin pathway of complement. Its deficiency is classified as a primary immunodeficiency associated to pyogenic bacterial infections, inflammatory lung disease, and autoimmunity. In Europeans, MASP-2 deficiency, due to homozygosity for c.359A > G (p.D120G), occurs in 7 to 14/10,000 individuals. We analyzed the presence of the p.D120G mutation in adults (increasing the sample size of our previous studies) and children. Different groups of patients (1495 adults hospitalized with community-acquired pneumonia, 186 adults with systemic lupus erythematosus, 103 pediatric patients with invasive pneumococcal disease) and control individuals (1119 healthy adult volunteers, 520 adult patients without history of relevant infectious diseases, and a pediatric control group of 311 individuals) were studied. Besides our previously reported MASP-2-deficient healthy adults, we found a new p.D120G homozygous individual from the pediatric control group. We also reviewed p.D120G homozygous individuals reported so far: a total of eleven patients with a highly heterogeneous range of disorders and nine healthy controls (including our four MASP-2-deficient individuals) have been identified by chance in association studies. Individuals with complete deficiencies of several pattern recognition molecules of the lectin pathway (MBL, collectin-10 and collectin-11, and ficolin-3) as well as of MASP-1 and MASP-3 have also been reviewed. Cumulative evidence suggests that MASP-2, and even other components of the LP, are largely redundant in human defenses and that individuals with MASP-2 deficiency do not seem to be particularly prone to infectious or autoimmune diseases.

Lethal Influenza in Two Related Adults with Inherited GATA2 Deficiency.

The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.

Saharan dust and the impact on adult and elderly allergic patients: the effect of threshold values in the northern sector of Gran Canaria, Spain.

Gran Canaria Island is frequently impacted by Saharan dust, a health hazard of particular concern to the island population and health agencies. Airborne mineral dust has the severest impact on the higher age groups of the population, and those with respiratory conditions; despite that, on average, the ambient particulate matter (PM) concentrations fall within international PM guidelines. During 2010 and 2011, an epidemiological survey, in parallel with an air quality study, was conducted at the Dr Negrín hospital in Gran Canaria. This included the quarterly monitoring of outpatients and recording of emergency patients with respiratory diseases, together with the measurement of aerosol, meteorological, and PM-related air quality levels. The finer more toxic particles were collected with PM2.5 (particulate matter with aerodynamic diameter less than 2.5 µm) aerosol samplers. The filter samples were gravimetrically and chemically analyzed for their elemental, water-soluble ions, carbon, and mineralogical contents. Individual particle morphology was measured by Scanning Electron Microscopy. Statistical analysis of the chemical and clinical data included the analysis of variance and calculation of Spearman correlation coefficients. No statistically significant relations were found between the allergic control group, the emergency room admissions, pulmonary conditions, medication, and elevated Saharan dust levels. However, changing environmental conditions, such as an increase in humidity or a reduction in ambient air temperature made a significant difference to the outcomes recorded on the health statements of the allergic and respiratory illness groups of the Gran Canary population.

Pneumonia presenting with organ dysfunctions: Causative microorganisms, host factors and outcome.

Community-acquired pneumonia (CAP) is a serious infection that may occasionally rapidly evolve provoking organ dysfunctions. We aimed to characterize CAP presenting with organ dysfunctions at the emergency room, with regard to host factors and causative microorganisms, and its impact on 30-day mortality. 460 of 4070 (11.3%) CAP patients had ≥2 dysfunctions at diagnosis, with a 30-day mortality of 12.4% vs. 3.4% in those with one or no dysfunctions. Among them, the most frequent causative microorganisms were Streptococcus pneumoniae, gram-negatives and polymicrobial etiology. Independent host risk factors for presenting with ≥2 dysfunctions were: liver (OR 2.97) and renal diseases (OR 3.91), neurological disorders (OR 1.86), and COPD (OR 1.30). Methicillin-resistant Staphylococcus aureus (OR 6.41) and bacteraemic episodes (OR 1.68) had the higher independent risk among microorganisms. The number of organ dysfunctions vs. none increased at 30-day mortality: three organs (OR 11.73), two organs (OR 4.29), and one organ (OR 2.42) whereas Enterobacteria (OR 3.73) were also independently related to mortality. The number of organ dysfunctions was the strongest 30-day mortality risk factor while Enterobacteriaceae was also associated with poorer outcome. The assessment of organ dysfunctions in CAP should be implemented for management, allocation and treatment decisions on initial evaluation.

Predictors of Severe Sepsis among Patients Hospitalized for Community-Acquired Pneumonia.

BACKGROUND: Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP). OBJECTIVE: To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP. RESULTS: We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07-1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50-2.04) and renal disease (OR, 1.57; 95% CI, 1.21-2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52-0.73). Bacteremia (OR, 1.37; 95% CI, 1.05-1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31-1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10-2.49) were associated with severe sepsis CAP. CONCLUSIONS: CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.

Sensitivity, Specificity, and Positivity Predictors of the Pneumococcal Urinary Antigen Test in Community-Acquired Pneumonia.

RATIONALE: Detection of the C-polysaccharide of Streptococcus pneumoniae in urine by an immune-chromatographic test is increasingly used to evaluate patients with community-acquired pneumonia. OBJECTIVES: We assessed the sensitivity and specificity of this test in the largest series of cases to date and used logistic regression models to determine predictors of positivity in patients hospitalized with community-acquired pneumonia. METHODS: We performed a multicenter, prospective, observational study of 4,374 patients hospitalized with community-acquired pneumonia. MEASUREMENTS AND MAIN RESULTS: The urinary antigen test was done in 3,874 cases. Pneumococcal infection was diagnosed in 916 cases (21%); 653 (71%) of these cases were diagnosed exclusively by the urinary antigen test. Sensitivity and specificity were 60 and 99.7%, respectively. Predictors of urinary antigen positivity were female sex; heart rate≥125 bpm, systolic blood pressure<90 mm Hg, and SaO2<90%; absence of antibiotic treatment; pleuritic chest pain; chills; pleural effusion; and blood urea nitrogen≥30 mg/dl. With at least six of all these predictors present, the probability of positivity was 52%. With only one factor present, the probability was only 12%. CONCLUSIONS: The urinary antigen test is a method with good sensitivity and excellent specificity in diagnosing pneumococcal pneumonia, and its use greatly increased the recognition of community-acquired pneumonia due to S. pneumoniae. With a specificity of 99.7%, this test could be used to direct simplified antibiotic therapy, thereby avoiding excess costs and risk for bacterial resistance that result from broad-spectrum antibiotics. We also identified predictors of positivity that could increase suspicion for pneumococcal infection or avoid the unnecessary use of this test.

Educational climate perception by preclinical and clinical medical students in five Spanish medical schools.

OBJECTIVE: The purpose of this study was to investigate student's perceptions of Educational Climate (EC) in Spanish medical schools, comparing various aspects of EC between the 2nd (preclinical) and the 4th (clinical) years to detect strengths and weaknesses in the on-going curricular reform. METHODS: This study utilized a cross-sectional design and employed the Spanish version of the "Dundee Ready Education Environment Measure" (DREEM). The survey involved 894 2nd year students and 619 4th year students from five Spanish medical schools. RESULTS: The global average score of 2nd year students from the five medical schools was found to be significantly higher (116.2±24.9, 58.2% of maximum score) than that observed in 4th year students (104.8±29.5, 52.4% of maximum score). When the results in each medical school were analysed separately, the scores obtained in the 2nd year were almost always significantly higher than in the 4th year for all medical schools, in both the global scales and the different subscales. CONCLUSIONS: The perception of the EC by 2nd and 4th year students from five Spanish medical schools is more positive than negative although it is significantly lower in the 4th year. In both years, although more evident in the 4th year, students point out the existence of several important "problematic educational areas" associated with the persistence of traditional curricula and teaching methodologies. Our findings of this study should lead medical schools to make a serious reflection and drive the implementation of the necessary changes required to improve teaching, especially during the clinical period.