Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

An in-silico analysis reveals further evidence of an aggressive subset of lung carcinoids sharing molecular features of high-grade neuroendocrine neoplasms.

Little is known as to whether there may be any pathogenetic link between pulmonary carcinoids and neuroendocrine carcinomas (NECs). A gene signature we previously found to cluster pulmonary carcinoids, large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), and which encompassed MEN1, MYC, MYCL1, RICTOR, RB1, SDHA, SRC and TP53 mutations or copy number variations (CNVs), was used to reclassify an independent cohort of 54 neuroendocrine neoplasms (NENs) [31 typical carcinoids (TC), 11 atypical carcinoids (AC) and 12 SCLC], by means of transcriptome and mutation data. Unsupervised clustering analysis identified two histology-independent clusters, namely CL1 and CL2, where 17/42 (40.5%) carcinoids and all the SCLC samples fell into the latter. CL2 carcinoids affected survival adversely, were enriched in T to G transversions or T > C/C > T transitions in the context of specific mutational signatures, presented with at least 1.5-fold change (FC) increase of gene mutations including TSC2, SMARCA2, SMARCA4, ERBB4 and PTPRZ1, differed for gene expression and showed epigenetic changes in charge of MYC and MTORC1 pathways, cellular senescence, inflammation, high-plasticity cell state and immune system exhaustion. Similar results were also found in two other independent validation sets comprising 101 lung NENs (24 carcinoids, 21 SCLC and 56 LCNEC) and 30 carcinoids, respectively. We herein confirmed an unexpected sharing of molecular traits along the spectrum of lung NENs, with a subset of genomically distinct aggressive carcinoids sharing molecular features of high-grade neuroendocrine neoplasms.

Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is an ultra-rare, slowly progressive neoplastic cystic disease, belonging to the group of PEComas. It can occur sporadically or associated to tuberous sclerosis complex disease and affects mainly women in child-birth age. Dyspnoea is the most frequent symptom referred to the time of diagnosis, however spontaneous pneumothorax may be a typical presentation associated to extrathoracic manifestations, such as renal angiomyolipomas. In the last decade, important advances in understanding molecular mechanisms underlying the LAM pathogenesis have been reached. It has allowed to obtain improvements in the research of novel biomarkers, treatment and a better management of the disease.

Post-recovery impact of the second and third SARS-CoV-2 infection waves on healthcare resource utilization in Lombardy, Italy.

The administrative claims database of the Italian region Lombardy, the first in Europe to be hit by the SARS-CoV-2 pandemic, was employed to evaluate the impact on healthcare resource utilization following recovery from the second (mainly alpha-related variant) and third (delta-related) infection waves. 317,164 individuals recovered from the infection and became negative after the second wave, 271,180 after the third. Of them, 1571 (0.5%) and 1575 (0.6%) died in the first 6 post-negativization months. In the remaining cases (315,593 after the second wave and 269,605 after the third), hospitalizations, attendances to emergency rooms and outpatient visits were compared with those recorded in the same pre-pandemic time periods in 2019. Dispensation of drugs as well as of imaging, and functional and biochemical diagnostic tests were also compared as additional proxies of the healthcare impact of the SARS-CoV-2 infection waves. Following both waves, hospitalizations, attendances at emergency rooms, and outpatient visits were similar in number and rates to the pre-pandemic periods. However, there was an increased dispensation a number of drugs and diagnostic tests, particularly those addressing the cardiorespiratory and blood systems. In a large region such as Lombardy taken as a relevant model because early and severely hit by the SARS-CoV-2 pandemic, the post-COVID burden on healthcare facilities was mildly relevant in cases who recovered from the second and third infection waves regarding such pivotal events as deaths, hospitalizations, and need for emergency room and outpatient visits, but was high regarding the dispensation of some drug classes and types of diagnostic tests.

Presumed Takotsubo syndrome is associated with high in-hospital mortality in very elderly frail females: a case series.

Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach.

What to expect from the ERS International Congress 2023.

This article provides an overview of the reasons to attend the 2023 ERS Congress, including a summary of the ECM session and the NEXT programme. https://bit.ly/46ghP4g.

Ejection fraction at hospital admission stratifies mortality risk in HFmrEF patients aged ≥ 70 years: a retrospective analysis from a tertiary university institution.

BACKGROUND: During the last few years, increasing focus has been placed on heart failure with mildly reduced ejection fraction (HFmrEF), an intermediate phenotype from preserved to reduced ejection fraction (EF). However, clinical features and outcome of HFmrEF in elderly patients aged ≥ 70 yrs have been poorly investigated. METHODS: The present study retrospectively included all consecutive patients aged ≥ 70 yrs discharged from our Institution with a first diagnosis of HFmrEF, between January 2020 and November 2020. All patients underwent transthoracic echocardiography. The primary outcome was all-cause mortality, while the secondary one was the composite of all-cause mortality + rehospitalization for all causes over a mid-term follow-up. RESULTS: The study included 107 HFmrEF patients (84.3 ± 7.4 yrs, 61.7% females). Patients were classified as "old" (70-84 yrs, n = 55) and "oldest-old" (≥ 85 yrs, n = 52) and separately analyzed. As compared to the "oldest-old" patients, the "old" ones were more commonly males (58.2% vs 17.3%, p < 0.001), with history of coronary artery disease (CAD) (54.5% vs 15.4%, p < 0.001) and significantly lower EF (43.5 ± 2.7% vs 47.3 ± 3.6%, p < 0.001) at hospital admission. Mean follow-up was 1.8 ± 1.1 yrs. During follow-up, 29 patients died and 45 were re-hospitalized. Male sex (HR 6.71, 95% CI 1.59-28.4), history of CAD (HR 5.37, 95% CI 2.04-14.1) and EF (HR 0.48, 95% CI 0.34-0.68) were independently associated with all-cause mortality in the whole study population. EF also predicted the composite of all-cause mortality + rehospitalization for all causes. EF < 45% was the best cut-off value to predict both outcomes. CONCLUSIONS: EF at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFmrEF patients over a mid-term follow-up.

Two years of SARS-CoV-2 pandemic and COVID-19 in Lombardy, Italy.

Lombardy, the largest and most densely populated Italian region, was severely hit in February 2020 by the first pandemic wave of SARS-CoV-2 and associated COVID-19. Since then, additional infection waves spread in the region. The aim of this study was to compare the first with the subsequent waves using the administrative database of the Lombardy Welfare directorate. In the time frames of the four 2020-2022 waves, the absolute number of infected cases, sites of management and crude mortality rate associated with SARS-CoV-2 positivity were extracted from the database. Infected cases progressively increased in the region by approximately 5-fold in the second versus the first wave, 4-fold in the third and 20-fold during the most recent wave mainly associated with the omicron variant. The crude death decreased from 18.7% in the first to 2% in the second and third wave to reach a 0.3% nadir at the time of the fourth wave. This study confirms that in Lombardy outcomes of public health and health-care relevance such as deaths and number of hospitalizations declined dramatically across the four virus waves and reached very low values in 2022 when, at variance with the first three SARS-CoV-2 waves, the majority of infected cases had been previously vaccinated.

Comparison of clinical scoring to predict mortality risk in mild-to-moderate idiopathic pulmonary fibrosis.

BACKGROUND: During the last decade, a number of clinical scores, such as Gender-Age-Physiology (GAP) Index, TORVAN Score and Charlson Comorbidity Index (CCI), have been separately used to measure comorbidity burden in idiopathic pulmonary fibrosis (IPF). However, no previous study compared the prognostic value of these scores to assess mortality risk stratification in IPF patients with mild-to-moderate disease. METHODS: All consecutive patients with mild-to-moderate IPF who underwent high-resolution computed tomography, spirometry, transthoracic echocardiography and carotid ultrasonography at our Institution, between January 2016 and December 2018, were retrospectively analyzed. GAP Index, TORVAN Score and CCI were calculated in all patients. Primary endpoint was all-cause mortality, whereas secondary endpoint was the composite of all-cause mortality and rehospitalizations for all-causes, over medium-term follow-up. RESULTS: Seventy IPF patients (70.2±7.4 yrs, 74.3% males) were examined. At baseline, GAP Index, TORVAN Score and CCI were 3.4±1.1, 14.7±4.1 and 5.3±2.4, respectively. A strong correlation between coronary artery calcification (CAC) and common carotid artery (CCA) intima-media thickness (IMT) (r=0.88), CCI and CAC (r=0.80), CCI and CCA-IMT (r=0.81), was demonstrated in the study group. Follow-up period was 3.5±1.2 years. During follow-up, 19 patients died and 32 rehospitalizations were detected. CCI (HR 2.39, 95% CI: 1.31-4.35) and heart rate (HR 1.10, 95% CI: 1.04-1.17) were independently associated with primary endpoint. CCI (HR 1.54, 95% CI: 1.15-2.06) predicted secondary endpoint, also. A CCI ≥6 was the optimal cut-off for predicting both outcomes. CONCLUSIONS: Due to the increased atherosclerotic and comorbidity burden, IPF patients with CCI ≥6 at an early-stage disease have poor outcome over medium-term follow-up.

Post-COVID condition: dispensation of drugs and diagnostic tests as proxies of healthcare impact.

With the goal to increase knowledge on the healthcare impact of the post-COVID-19 condition we exploited the administrative claims database of Lombardy, the largest Italian region and the first after China to be heavily hit by the SARS-CoV-2 pandemic in February-May 2020. We chose to employ the dispensation of drugs and diagnostic tests as proxies of the impact of the post-COVID condition in 46,574 cases who recovered from COVID-19 and were negative at PCR testing within June 20, 2020. Data were obtained throughout the 18-month post-negativization period until December 2021 and results on the use of drugs and diagnostic tests were compared with those accrued in the same cases during the pre-COVID period in July-December 2019. After an increase in the first semester after SARS-CoV-2 negativization (July-December 2020), trends in the dispensation of drugs according to the broad ATC classes and of diagnostic tests decreased or remained substantially stable. However, dispensation of drugs for acid related disorders (A02), diabetes (A10), heparins (B01AB), direct oral anticoagulants (B01AP), antipsychotics (N05A), antidepressants (N06A) and for obstructive airways diseases (R03) was still higher than in the pre-COVID period. These findings, based upon drug and diagnostic test dispensation as proxies of the healthcare impact of the post-COVID condition, show that in a substantial proportion of recovered cases the post-COVID condition is active and clinically relevant 18 months after the acute disease. The findings also provide indirect evidence of the body organs and systems more compromised in the post-COVID period.

Prognostic role of CHA2DS2-VASc score for mortality risk assessment in non-advanced idiopathic pulmonary fibrosis: a preliminary observation.

During the last decade, the CHA2DS2-VASc score has been used for stratifying the mortality risk in both atrial fibrillation (AF) and non-AF patients. However, no previous study considered this score as a prognostic indicator in non-AF patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). All consecutive non-AF patients with mild-to-moderate IPF, diagnosed between January 2016 and December 2018 at our Institution, entered this study. All patients underwent physical examination, blood tests, spirometry, high-resolution computed tomography and transthoracic echocardiography. CHA2DS2-VASc score, Gender-Age-Physiology (GAP) index and Charlson Comorbidity Index (CCI) were determined in all patients. Primary endpoint was all-cause mortality, while the secondary endpoint was the composite of all-cause mortality and rehospitalizations for all causes over mid-term follow-up. 103 consecutive IPF patients (70.7 ± 7.3 yrs, 79.6% males) were retrospectively analyzed. At the basal evaluation, CHA2DS2-VASc score, GAP index and CCI were 3.7 ± 1.6, 3.6 ± 1.2 and 5.5 ± 2.3, respectively. Mean follow-up was 3.5 ± 1.3 yrs. During the follow-up period, 29 patients died and 43 were re-hospitalized (44.2% due to cardiopulmonary causes). On multivariate Cox regression analysis, CHA2DS2-VASc score (HR 2.15, 95% CI 1.59-2.91) and left ventricular ejection fraction (LVEF) (HR 0.91, 95% CI 0.86-0.97) were independently associated with all-cause mortality in IPF patients. CHA2DS2-VASc score (HR 1.66, 95% CI 1.39-1.99) and LVEF (HR 0.94, 95% CI 0.90-0.98) also predicted the secondary endpoint in the same study group. CHA2DS2-VASc score > 4 was the optimal cut-off for predicting both outcomes. At mid-term follow-up, a CHA2DS2-VASc score > 4 predicts an increased risk of all-cause mortality and rehospitalizations for all causes in non-AF patients with mild-to-moderate IPF.

Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period.

Purpose: To investigate the clinical predictors of in-hospital mortality in hospitalized patients with Coronavirus disease 2019 (COVID-19) infection during the Omicron period. Methods: All consecutive hospitalized laboratory-confirmed COVID-19 patients between January and May 2022 were retrospectively analyzed. All patients underwent accurate physical, laboratory, radiographic and echocardiographic examination. Primary endpoint was in-hospital mortality. Results: 74 consecutive COVID-19 patients (80.0 ± 12.6 yrs, 45.9% males) were included. Patients who died during hospitalization (27%) and those who were discharged alive (73%) were separately analyzed. Compared to patients discharged alive, those who died were significantly older, with higher comorbidity burden and greater prevalence of laboratory, radiographic and echographic signs of pulmonary and systemic congestion. Charlson comorbidity index (CCI) (OR 1.76, 95%CI 1.07-2.92), neutrophil-to-lymphocyte ratio (NLR) (OR 1.24, 95%CI 1.10-1.39) and absence of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) therapy (OR 0.01, 95%CI 0.00-0.22) independently predicted the primary endpoint. CCI ≥7 and NLR ≥9 were the best cut-off values for predicting mortality. The mortality risk for patients with CCI ≥7, NLR ≥9 and not in ACEI/ARBs therapy was high (86%); for patients with CCI <7, NLR ≥9, with (16.6%) or without (25%) ACEI/ARBs therapy was intermediate; for patients with CCI <7, NLR <9 and in ACEI/ARBs therapy was of 0%. Conclusions: High comorbidity burden, high levels of NLR and the undertreatment with ACEI/ARBs were the main prognostic indicators of in-hospital mortality. The risk stratification of COVID-19 patients at hospital admission would help the clinicians to take care of the high-risk patients and reduce the mortality.

Sarcopenia in idiopathic pulmonary fibrosis: a prospective study exploring prevalence, associated factors and diagnostic approach.

BACKGROUND: Sarcopenia gained importance in the evaluation of patients with chronic respiratory diseases, including idiopathic pulmonary fibrosis (IPF), since it may impact negatively on clinical outcomes. AIM: Aim of this study is to evaluate the prevalence and factors associated with sarcopenia, defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) 2019 definition, and to evaluate the prevalence of the single criteria that define the EWGSOP2 definition (muscle strength, muscle quantity and physical performance), in a cohort of consecutive patients with IPF prospectively followed up in 9 hospitals in Northern Italy between December 2018 and May 2021. METHODS: Enrolled patients underwent an extensive pulmonary and nutritional assessment, including bioelectrical impedance analysis, dynamometry and 4-m gait speed test, both at IPF diagnosis and at 6-month follow-up. RESULTS: Out of the 83 patients (81% males, mean age 72.5 years) with IPF at disease diagnosis enrolled in the study, 19 (22.9%) showed sarcopenia, including 2 (2.4%) with severe sarcopenia, 5 (6.0%) with confirmed sarcopenia and 12 (14.5%) with probable sarcopenia. Sarcopenia was associated with a significantly higher severity of the disease and sedentary lifestyle, while no differences were observed in regards to body mass index, history of weight loss and comorbidities between patients with and without sarcopenia. Out of the 64 patients without sarcopenia at baseline, 16 cases showed alteration of muscle quantity and/or physical performance. In the 51 patients with complete data at 6-month follow-up, there were no cases of severe sarcopenia, 1 case (2.0%) showed confirmed sarcopenia, while the prevalence of probable sarcopenia was 19.6% (10 cases). No differences in regards to antifibrotic treatment received and onset of gastrointestinal side effects were observed between patients with and without sarcopenia at follow-up. CONCLUSIONS: The prevalence of sarcopenia in patients with IPF both at diagnosis and at 6-month follow-up was low but not negligible and was associated with higher severity of the disease and sedentary lifestyle. In IPF patients, a comprehensive diagnostic work-up including all the criteria defining the EWGSOP2 definition might be more useful than a series testing for prompt recognition of nutritional and physical performance abnormalities.