Usefulness of a predictive model to hospitalize patients with low-risk community-acquired pneumonia.

INTRODUCTION: A high proportion of patients with low-risk community-acquired pneumonia (CAP) (classes I-III of the Pneumonia Severity Index) are hospitalized. The purpose of this study was to determine whether validated severity scales are used in clinical practice to make admission decisions, identify the variables that influence this decision, and evaluate the potential predictive value of these variables. MATERIALS AND METHODS: A prospective, observational study of patients ≥ 18 years of age with a diagnosis of low-risk CAP hospitalized or referred from the Emergency Department to outpatient consultations. A multivariate logistic regression predictive model was built to predict the decision to hospitalize a patient. RESULTS: The study population was composed of 1,208 patients (806 inpatients and 402 outpatients). The severity of CAP was estimated in 250 patients (20.7%). The factors that determined hospitalization were "abnormal findings in complementary studies" (643/806: 79.8%; due to respiratory failure in 443 patients) and "signs of clinical deterioration" [64/806 (7.9%): hypotension (16/64, 25%); hemoptoic expectoration (12/64, 18.8%); tachypnea (10/64, 15.6%)]. In total, ambulatory management was not contraindicated in 24.7% of hospitalized patients (199). The predictive model built to decide about hospitalization had a good power of discrimination (AUC 0.876; 95%CI: 0.855-0.897). CONCLUSIONS: Scales are rarely used to estimate the severity of CAP at the emergency department. The decision to hospitalize or not a patient largely depends on the clinical experience of the physician. Our predictive model showed a good power to discriminate the patients who required hospitalization. Further studies are warranted to validate these results.

A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity.

Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were present in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Co-expression network analysis adds further support to these findings, by detecting modules specifically correlated with severity involved in the abovementioned biological routes; this analysis also provides new candidate genes that might be tested as biomarkers in future studies. We also found tissue specific severity-related signatures mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.

Characteristics of Patients with Lymphangioleiomyomatosis and Pleural Effusion: A Systematic Review.

The characteristics of patients with lymphangioleiomyomatosis (LAM) are poorly defined, as they may present with or without pleural effusion (PE). We performed a systematic review across four electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of LAM. Case descriptions and retrospective studies were included, unrestricted by year of publication. The review consisted of 94 studies (199 patients) spanning a period of nearly 55 years. The median age was 38 years (range: 1 month to 69 years), and 79.7% were between 21 and 50 years old. All cases had dyspnea, 95% had a cough, and 87.5% had chest pain. PE was exudative chylothorax, usually unilateral (76%) and right-sided, predominantly lymphocytic, and with proportionately higher levels of proteins than lactate dehydrogenase. Sirolimus was effective in all cases, completely in 87%, and partially in 13%, although the number of patients receiving sirolimus was small. The present study confirmed that LAM and PE mainly occur in women of childbearing age (third to fifth decade of life). PE was usually unilateral and presented as a lymphocyte-predominant chylous exudate. The most effective treatment for PE seems to be sirolimus, although studies with larger series are needed to confirm this.

[Diabetes and obstructive sleep apnoea: A case-control study]. / Diabetes y apnea obstructiva del sueño. Un estudio de casos y controles.

INTRODUCTION: Obstructive sleep apnoea (OSA) and diabetes mellitus (DM) are very prevalent diseases frequently associated. Their coexistence is independently associated with an increased prevalence of cardiovascular comorbidities. As this association is underdiagnosed, it is necessary to optimise clinical suspicion by studying independent predictors of DM or prediabetes (preDM) in patients with OSA. METHOD: A simple randomised case-control study, matched for sex, body mass index (BMI) and age, aimed to study the association of OSA with DM and preDM and to identify independent predictors for both diseases in people with OSA. RESULTS: We included 208 cases with OSA and 208 controls without OSA. In the former, 18.8% had DM compared to only 10.1% in the latter (P=.00). Prevalence of preDM was 41.8% vs. 10.6%, respectively (P=.00). One hundred and twenty-four cases (59.6%) reported excessive daytime sleepiness (EDS) (Epworth scale, 10.5±3.1) vs. 24.5% of the control group (Epworth scale, 6.6±2.9). Apnoea-hypopnoea index (AHI) and O2 desaturation indices (IDO, CT90 and CT80) were significantly higher in the case group. The risk of MD was related to age, nocturnal hypoxaemia and EDS. The risk of pre-MD was related to BMI and AHI. CONCLUSIONS: OSA is associated with DM and preDM. Age, nocturnal hypoxaemia and EDS are predictors of DM. BMI and AHI are predictors of pre-MD.

Use of Mycophenolate mofetil for the treatment of fibrotic hypersensitivity pneumonitis.

INTRODUCTION: The optimal treatment of fibrosing hypersensitivity pneumonitis (fHP) is not well understood. The aim of the study was to obtain information about the usefulness of mycophenolate mofetil (MMF) in its treatment. MATERIAL AND METHODS: Quasi-experimental analysis of patients diagnosed with fHP and treated with MMF for one year, in a single centre. From the start of treatment, data collection was prospective. RESULTS: Seventy-three patients were included and 58 completed the study. FVC% and DLCO% decreased until starting MMF (year -1 to year 0). After completion of treatment (year 1), FVC% stabilised (p=0.336) and DLCO% improved significantly (p=0.004) compared to year 0. Dyspnoea, number of patients without corticosteroids and mean corticosteroid dose also improved significantly (p<0.001 in all cases). Being male and having a history of tuberculosis were predictors of poor drug response [AUC = 0.89 (95%CI: 0.80-0.98)]. Forty-five adverse effects were observed in 34 patients (46.6%). In 4 cases (5.5%), the adverse effect was severe and required discontinuation of treatment. CONCLUSIONS: In patients with fHP, MMF improves lung function and dyspnoea and reduces both the number of patients requiring oral corticosteroids and their mean dose in those who completed 1 year of treatment. The model constructed predicts which patients will respond poorly to treatment, with good discriminative ability and only a small percentage of patients will not tolerate treatment. Further prospective, randomised clinical trials are needed to define the role of this treatment in fHP.

Hypersensitivity pneumonitis: application of a new diagnostic algorithm to a time series of the disease.

BACKGROUND: The diagnostic criteria for Hypersensitivity pneumonitis (HP) have changed over time. Our aim is to apply a recent diagnostic algorithm to a historical series of patients diagnosed with HP to assess its distribution according to current diagnostic criteria and the diagnostic confidence achieved. RESEARCH DESIGN AND METHODS: Application to each patient the algorithm criteria. The diagnosis was HP (≥90%), provisional high (70-89%) or low confidence (51-69%) or non-HP (unlikely) (≤50%); or HP, provisional or non-HP, if they had lung biopsy. RESULTS: 129 patients [mean age 64 ± 12 years; 79 (61.2%) women] were included of which 16 (12.4%) were diagnosed on the basis of high clinical suspicion. After applying the algorithm, 106 patients (82.2%) could be evaluated and 83 (78.3%) had a diagnosis of HP or high confidence. Lung biopsy was able to establish a diagnosis of certainty in another 21 patients and a provisional diagnosis in 9 more [total, 113 (87.6%)]. The 16 patients without strict diagnostic criteria for HP had a low confidence diagnosis. A total of 56 lung biopsies (64.4%) could have been avoided according to the new guidelines. CONCLUSIONS: The application of this algorithm achieves a high diagnostic yield in HP, significantly reducing the number of lung biopsies required.

[Relationship between obstructive sleep apnea and type 2 diabetes mellitus]. / Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2.

INTRODUCTION: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. METHODS: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. RESULTS: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5-13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. CONCLUSIONS: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk.

Effect of an intensive tobacco cessation program on the smoker narrative: A content analysis and grounded theory.

INTRODUCTION: The smoker's narrative during smoking quitting provides insight into aspects not fully explored in daily clinical practice. The aim of the study was to analyze the smoker narrative using two types of methodologies: content analysis and grounded theory, before and after smoking cessation intervention, provided to the smoker in a specialized Smoking Cessation Unit accredited by the Spanish Society of Pneumology and Thoracic Surgery. METHODS: A prospective observational study of current smokers included in a tobacco cessation program between 2017 and 2020 was conducted at the Smoking Cessation Unit of Santiago de Compostela Health Area, Spain. Routine clinical variables and patient narrative data were collected. A descriptive analysis of the sample, the content of the textual corpus, and a grounded theory were performed in semi-structured interviews at baseline and at follow-up at 6 months. RESULTS: A total of 116 patients were included (mean age 55.6 ± 10.6 years; 56.9% male; mean nicotine dependence score 5.7 ± 1.6). Quantitative analysis of the narrative shows that the most frequent phrases and words are associated with smoking, nicotine craving, and predisposition for smoking cessation. After the intervention, phrases related to the manifestation of abstinence, response to pharmacological treatment, and self-perception of smoking cessation were predominant. In the qualitative analysis, the most frequent categories in the smoker's textual corpus were dependence, motivation, and emotionality, which decreased after the intervention (11.4%, 21.4%, and 9.9%, respectively) accompanied by increased satisfaction (19.2%) and the manifestation of abstinence (21.5%). CONCLUSIONS: Motivation, nicotine dependence, and sensitivity to emotions are all closely intertwined in the current smoker narrative and can be modified as a consequence of treatment.

Analysis of the quality of e-Consultations in chronic obstructive pulmonary disease.

INTRODUCTION: The quality of e-Consultations in the COPD is unknown. The objectives of this study were (i) to evaluate the quality of referrals; (ii) to define the characteristics of patients referred from Primary Care (PC) to the Unit of Pulmonology; and (iii) to describe differences between accepted and rejected patients. METHODS: A retrospective, observational study of e-Consultations requested by PC for suspected COPD throughout 2022. To quantify the quality of the e-Consultations, an arbitrary scale of 12 variables (score 0-10) was created. RESULTS: In total, 384 e-Consultations were reviewed, of which 167 (43.5 %) resulted in a face-to-face visit, and 217 (56.5 %) were rejected. No differences were observed between the two types of patients, except for confirmations of diagnostic suspicion of COPD [significantly higher in accepted patients (p = 0.042)]; physical examination data of rejected patients (more data provided; p = 0.015); and lung function (significantly better in rejected patients). The mean quality of referrals was acceptable (5.6 ± 2.1 score): 121 (31.3 %) had insufficient quality; 118 (30.5 %) acceptable; 75 (19.4 %) good, and 30 (7.8 %) excellent. Quality was low in half of the variables analyzed (6/12); acceptable in 3, and good in another 3. The capacity of resolution of referrals was good (one e-Consultation) in 199 requests (66.1 %); deficient (two e-Consultations) in 72 (23.9 %), and poor (≥3 e-Consultations) in 30 (10 %). Overdiagnosis was 40.2 % (86/214 e-Consultations). The risk could be classified in 247 patients (64.3 %; 135 low-risk; 90 high-risk). CONCLUSIONS: When adequate information is provided, e-Consultations help identify different levels of severity. However, the quality and capacity of resolution of referrals were suboptimal, with a high percentage of overdiagnoses.

Non-specific pleuritis: long-term follow-up outcomes.

BACKGROUND: The definitive etiology of nonspecific pleuritis (NSP), the influence of the type of pleural biopsy on clinical results and the minimum duration of follow-up is controversial. RESEARCH DESIGN AND METHODS: A retrospective, observational study of patients ≥ 18 years with NSP confirmed by closed pleural biopsy (CPB), local anesthesia pleuroscopy (LAP), or video-assisted thoracic surgery (VATS). RESULTS: A total of 167 patients were included (mean follow-up, 14.4 months), of which 25 (15%) were diagnosed within one month; [15 (60%) malignant]. Of the remaining 142 pleural effusions (PEf), 69 (48.6%) were idiopathic; 49 (34.5%) not-malignant and 24 (16.9%) malignant (4 mesotheliomas and 20 metastasic). The diagnosis of NSP was established by CPB (7; median time to diagnosis, 9.4 months), LAT (5; 15.8 months), and VATS (8; 13.5 months) (p = 0.606). Sixty-eight patients (40.7%) died during follow-up (mean time, 12 months). CONCLUSIONS: In a substantial percentage of patients diagnosed with NSP, a definitive diagnosis will not be obtained, a relevant number of patients will develop a malignant PEf. The diagnostic procedure used for the diagnosis of NSP does not seem to influence delay in the diagnosis of malignant PEf. The data obtained suggest that follow-up should be maintained for at least 24 months.

Combining clinical and analytical parameters improves prediction of malignant pleural effusion.

PURPOSE: The usefulness of a panel of tumour markers and clinical-radiological criteria for diagnosing malignant pleural effusion (MPE) is not clearly stated. Our purpose was to assess the performance of those parameters in the diagnosis of MPE. METHODS: Consecutive patients with exudative PE were enrolled and divided into two groups: MPE and non-MPE. Logistic regression analysis was used to estimate the probability of MPE. Four prognostic models were considered: (1) clinical-radiological variables; (2) analytical variables; (3) combination of clinical and analytical variables; and (4) simpler model removing some analytical variables. Calibration and discrimination (receiver operating characteristics curves and AUC) were performed. RESULTS: A total of 491 pleural exudates were included: tuberculous (n = 72), malignant (n = 211), parapneumonic (n = 115), empyemas (n = 32), or miscellaneous (n = 61). The AUC obtained with Model 1 (absence of chest pain and fever and radiological images compatible with malignancy), Model 2 (CEA, NSE, CYFRA 21-1, and TPS), Model 3 (sum of the variables of models 1 and 2), and Model 4 (the variables of model 1 plus CEA) were 0.918, 0.832, 0.952 (all with a P < 0.05), and 0.939 (P < 0.01 compared to models 1 and 2), respectively. The correct classification rate for Models 1, 2, 3, and 4, was 87.2, 79.5, 88.4, and 87.6 %, respectively. CONCLUSIONS: All models analysed had a good diagnostic yield for MPE, being greater in those that combined radiological and analytical criteria. Although Model 3 obtained a higher yield, the simplest model (Model 4) is very attractive due to its simplicity of use in daily practice.

Characteristics of pleural effusion due to amyloidosis.

The characteristics of patients with pleural amyloidosis (PA) are poorly known. A systematic review was performed of studies reporting clinical findings, pleural fluid (PF) characteristics, and the most effective treatment of PA. Case descriptions and retrospective studies were included. The review included 95 studies with a total sample of 196 patients. The mean age was 63 years, male/female ratio was 1.6:1, and 91.9% of patients were >50 years. The most common symptom was dyspnea (88 patients). PF was generally serious (63%), predominantly lymphocytic, and with the biochemical characteristics of transudates (43.4%) or exudates (42.6%). Pleural effusion was generally bilateral (55%) and <1/3 of the hemithorax (50%), although in 21% pleural effusion (PE) exceeded 2/3. Pleural biopsy was performed in 67 patients (yield: 83.6%; 56/67) and was positive in 54% of exudates and 62.5% of unilateral effusions. Of the 251 treatments prescribed, only 31 were effective (12.4%). The combination of chemotherapy and corticosteroids was effective in 29.6% of cases, whereas talc pleurodesis was effective in 21.4% and indwelling pleural catheter in 75% of patients (only four patients). PA is more frequent in adults from 50 years of age. PF is usually bilateral, serous, and indistinctly a transudate or exudate. A pleural biopsy can aid in diagnosis if effusion is unilateral or an exudate. Treatments are rarely effective and there may be definitive therapeutic options for PE in these patients.

Development of prognostic models to estimate the probability of lung injury one year after COVID-19-related hospitalization-a prospective study.

Background: Long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection still under study. The objectives of this study were to identify persistent pulmonary lesions 1 year after coronavirus disease 2019 (COVID-19) hospitalization and assess whether it is possible to estimate the probability that a patient develops these complications in the future. Methods: A prospective study of ≥18 years old patients hospitalized for SARS-COV-2 infection who develop persistent respiratory symptoms, lung function abnormalities or have radiological findings 6-8 weeks after hospital discharge. Logistic regression models were used to identify prognostic factors associated with a higher risk of developing respiratory problems. Models performance was assessed in terms of calibration and discrimination. Results: A total of 233 patients [median age 66 years [interquartile range (IQR): 56, 74]; 138 (59.2%) male] were categorized into two groups based on whether they stayed in the critical care unit (79 cases) or not (154). At the end of follow-up, 179 patients (76.8%) developed persistent respiratory symptoms, and 22 patients (9.4%) showed radiological fibrotic lesions with pulmonary function abnormalities (post-COVID-19 fibrotic pulmonary lesions). Our prognostic models created to predict persistent respiratory symptoms [post-COVID-19 functional status at initial visit (the higher the score, the higher the risk), and history of bronchial asthma] and post-COVID-19 fibrotic pulmonary lesions [female; FVC% (the higher the FVC%, the lower the probability); and critical care unit stay] one year after infection showed good (AUC 0.857; 95% CI: 0.799-0.915) and excellent performance (AUC 0.901; 95% CI: 0.837-0.964), respectively. Conclusions: Constructed models show good performance in identifying patients at risk of developing lung injury one year after COVID-19-related hospitalization.

A pulmonary rehabilitation program reduces hospitalizations in chronic obstructive pulmonary disease patients: A cost-effectiveness study.

BACKGROUND: Although pulmonary rehabilitation (PR) is recommended in patients with chronic obstructive pulmonary disease (COPD), there is a scarcity of data demonstrating the cost-effectiveness and effectiveness of PR in reducing exacerbations. METHODS: A quasi-experimental study in 200 patients with COPD was conducted to determine the number of exacerbations 1 year before and after their participation in a PR program. Quality of life was measured using the COPD assessment test and EuroQol-5D. The costs of the program and exacerbations were assessed the year before and after participation in the PR program. The incremental cost-effectiveness ratio (ICER) was estimated in terms of quality-adjusted life years (QALYs). RESULTS: The number of admissions, length of hospital stay, and admissions to the emergency department decreased after participation in the PR program by 48.2%, 46.6%, and 42.5%, respectively (P < 0.001 for all). Results on quality of life tests improved significantly (P < 0.001 for the two tests). The cost of PR per patient and the cost of pre-PR and post-PR exacerbations were €1867.7 and €7895.2 and €4201.9, respectively. The PR resulted in a cost saving of €1826 (total, €365,200) per patient/year, and the gain in QALYs was+0.107. ICER was -€17,056. The total cost was <€20,000/QALY in 78% of patients. CONCLUSIONS: PR contributes to reducing the number of exacerbations in patients with COPD, thereby slowing clinical deterioration. In addition, it is cost-effective in terms of QALYs.

Pulmonary Manifestations of Primary Humoral Deficiencies.

Primary immunodeficiencies are a group of conditions characterized by developmental or functional alterations in the immune system caused by hereditary genetic defects. Primary immunodeficiencies may affect either the innate or the adaptive (humoral and cellular) immune system. Pulmonary complications in primary humoral deficiencies are frequent and varied and are associated with high morbidity and mortality rates. The types of complications include bronchiectasis secondary to recurrent respiratory infections and interstitial pulmonary involvement, which can be associated with autoimmune cytopenias, lymphoproliferation, and a range of immunological manifestations. Early detection is key to timely management. Immunoglobulin replacement therapy reduces the severity of disease, the frequency of exacerbations, and hospital admissions in some primary humoral deficiencies. Therefore, the presence of pulmonary disease with concomitant infectious and/or autoimmune complications should raise suspicion of primary humoral deficiencies and warrants a request for immunoglobulin determination in blood. Once diagnosis is confirmed; early immunoglobulin replacement therapy will improve the course of the disease. Further studies are needed to better understand the pathogenesis of pulmonary disease related to primary humoral deficiencies and favor the development of targeted therapies that improve the prognosis of patients.

Cost-Effectiveness of a New Outpatient Pulmonology Care Model Based on Physician-to-Physician Electronic Consultation.

Introduction: This study assesses the impact of an electronic physician-to-physician consultation program on the waiting list and the costs of a Pulmonology Unit. Materials and Methods: A prepost intervention study was conducted after a new ambulatory pulmonary care protocol was implemented and the capacity of the unit was adopted. In the new model, physicians at all levels of healthcare send electronic consultations to specialists. Results: In the preintervention year (2019), the Unit of Pulmonology attended 7,055 consultations (466 e-consultations and 6,589 first face-to-face visits), which decreased to 6,157 (3,934 e-consultations and 2,223 first face-to-face visits; 12.7% reduction) in the postintervention year (all were e-consultations). The mean wait time for the first appointment was 25.7 days in 2019 versus 3.2 days in 2021 (p < 0.001). In total, 43.5% of cases were solved via physician-to-physiciane-consultation. A total of 2,223 patients needed a face-to-face visit, with a mean wait time of 7.5 days. The mean of patients in the waiting listing decreased from 450.8 in 2019 to 44.8 in 2021 (90% reduction). The annual time devoted to e-consultations and first face-to-face visits following an e-consultation diminished significantly after the intervention (1,724 hours versus 2,312.8; 25.4% reduction). Each query solved via e-consultation represented a saving of €652.8, resulting in a total annual saving of €827,062. Conclusions: Physician-to-physiciane-consultations reduce waiting times, improve access of complex patients to specialty care, and ensure that cases are managed at the appropriate level. E-consultation reduces costs, which benefits both, society and the healthcare system.

Sarcoidosis. Disease progression based on radiological and functional course: Predictive factors.

BACKGROUND: Sarcoidosis is a multiorgan granulomatous disease with a variable course. OOBJECTIVES: The purpose of this study is to identify the patients that are more likely to experience disease progression. METHODS: A retrospective study in patients ≥18 years. Pulmonary function and radiological stage (Scadding criteria) were assessed at diagnosis, and at 1, 3 and 5 years. Sarcoidosis progression was established based on deterioration of radiological or pulmonary function (decrease ≥10% of FVC and/or ≥15% of diffusing capacity of the lung (DLCO). RESULTS: The sample included 277 caucasian patients [mean age, 50±13.6; 69.7% between 31-60 years; 56.3% men]. In total, 65% had stage II sarcoidosis, whereas only 8.3% had stage III/IV disease. Mean pulmonary function (FVC, FEV1, FEV1/FVC and DLCO) at diagnosis was 103±21.8, 96±22.2, 76.2±8 and 81.7±21.7, respectively. The percentage of patients with normal FVC and DLCO was 72.2% and 51.8%, respectively. Radiological stage did not change significantly during follow-up (5 years; p=0.080) and only progressed in 13 patients (5.7%). At 3 years, FVC improved, whereas DLCO exacerbated significantly (p<0.001 for the two). Disease progressed in 34.5% of the patients (57/165) whose pulmonary function and radiological stage were available (both baseline and at 3 years). Age was associated with disease progression [OR=1.04 (95%CI=1.01, 1.06)]. Risk increased by 4% for each year older a patient was at diagnosis. CONCLUSIONS: At 3 years, a third of patients experienced sarcoidosis progression. Age was the only factor associated with disease prognosis.

Characterisation of the blood RNA host response underpinning severity in COVID-19 patients.

Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. In this study, for the first time, we show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.

Impact of sleep apnoea-hypopnoea syndrome on diabetic neuropathy. A systematic review. / Impacto del síndrome de apnea-hipopnea del sueño en la neuropatía diabética. Revisión sistemática.

INTRODUCTION: Diabetes mellitus and sleep apnoea-hypopnoea syndrome appear to be related, but it is not well defined whether there is an increased risk of peripheral neuropathy in patients with both diseases. For this reason, we conducted a systematic review. METHODS: Bibliographic search in 3 electronic databases using a predefined strategy and the PRISMA methodology. Only original studies (any type of design) published from 2000 onwards in English, French, Portuguese or Spanish were included. A study quality scale was established. RESULTS: Twelve articles were selected, of which six studied type 2 diabetic patients. The overall prevalence of sleep apnoea-hypopnoea syndrome was 43.7% (1,559/3,564 patients). Diabetic neuropathy was more frequent in patients with sleep apnoea-hypopnoea syndrome in nine studies, although significantly only in four (60% vs 27%, P<.001; 64.5% vs 36%, P=.03; 37% vs 23.4%, P<.02; 66.6% vs 0%, P=.007). In one study, diabetic neuropathy was more frequent in patients without sleep apnoea-hypopnoea syndrome (although not statistically significant) and in 2 no comparison was made between patients with/without sleep apnoea/hypopnoea syndrome. CONCLUSIONS: The observed results suggest a relationship between diabetes mellitus and sleep apnoea-hypopnoea syndrome in the occurrence of diabetic neuropathy.

Evaluation of the impact of an integrated care pathway for pulmonary embolism: a quasi-experimental pre-post study.

BACKGROUND: An integrated care pathway (ICP) is intended to improve the management of prevalent resource-consuming, life-threatening diseases. The purpose of this study was to determine whether the quality of patient care improved with the establishment of a dedicated unit for pulmonary embolism (PE). METHODS: A quasi-experimental pre-post study (pre: years 2010-2013; post: 2015-2020; year 2014, "washing" period) of PE patients ≥18 years (January 2010-June 2020). The intervention involved the implementation of an ICP for PE. RESULTS: The sample was composed of 1,142 patients (510 pre-intervention and 612 post-intervention) without significant differences between the two populations. In the post-intervention period, significant reductions were observed in the median length of hospital stay (LOS) (8 vs. 6 days); time to start of oral anticoagulation therapy (4.5 vs. 3.5 days; P<0.001); and the percentage of patients with high-risk PE in whom recanalization was not contraindicated (66.7% vs. 96%; P=0.009). In-hospital and 30-day mortality decreased, although not significantly (4.5% vs. 2.8%; P=0.188; 6.1% vs. 5.2%; P=0.531, respectively). Multivariate logistic regression analysis showed that the median LOS intervention decreased significantly according to the service where patients were referred to, and with the use of the simplified PESI. During follow-up, lifelong anticoagulation was prescribed to a higher proportion of patients in the post-intervention period (30.7% vs. 69.3%; P<0.001). CONCLUSIONS: Although an ICP for PE does not reduce mortality significantly, it improves the quality of patient care.