Effect of SARS-CoV-2 infection on anti-HLA antibodies and de novo donor specific antibodies incidence in lung transplant recipients.

PURPOSE: There are no clear guidelines on how to handle immunosuppression in lung transplant recipients (LTRs) infected by SARS-CoV-2. Antimetabolite reduction with corticosteroid escalation is the most frequent strategy. The aim of this study was to determine the effect of this therapeutic approach on the incidence of de novo donor specific-antibodies (dnDSA). METHODS: We retrospectively analysed a cohort of 27 LTRs diagnosed with SARS-CoV-2 infection between September 2020 and April 2021 with available anti-HLA antibodies screening before and after infection. Managed as per the centre's SARS-CoV-2 protocol, the treatment modalities included specific virostatic treatment, convalescent plasma administration, reduction or discontinuation of mycophenolate and transient corticosteroid escalation initiated in the second week post-infection. RESULTS: All 27 patients received virostatics: 15 (55.6%) remdesivir and 12 (44.4%) favipiravir. In addition, 18 patients (66.7%) underwent convalescent plasma therapy. Of the 27 patients, 25 (92.6%) received mycophenolate as a part of their maintenance immunosuppressive regimen, which was temporarily reduced in 10 (37%) and discontinued in 15 LTRs (55.6%), the median resumption times for mycophenolate daily doses of at least 1000 mg being 13 days (IQR 11.0-63.5) and 59 days (IQR 26.0-130.0), respectively. Corticosteroids were escalated in 25 patients (92.6%), of whom 9 (33.3%) received IV methylprednisolone (median 80 mg/day; IQR 80-187.5) and 16 (59.3%) had oral prednisone adjusted (median 20 mg/day; IQR 16.3-38.8). The median time to revert to the corticosteroid dosage of ≤20 mg/day was 42 days (IQR 36.0-87.0). Notably, no dnDSA were detected in any LTR between 1 and 9 months from the onset of the SARS-CoV-2 infection. CONCLUSION: Our findings suggest that antimetabolite cessation with a transient corticosteroid escalation is a safe therapeutic strategy regarding anti-HLA dynamics in SARS-CoV-2 infected LTRs.

Worse Prognosis in the Symptomatic Patients With Lung Cancer - Czech Multicentric Study.

Background/Aim: This study aimed at contributing to a better diagnosis of lung cancer by analyzing the patient's symptoms and their linkage to other characteristics. Patients and Methods: We analyzed the data of 3,322 patients from LUCAS (LUngCAncerfocuS) National Registry of the Czech Republic. Overall survival was assessed using the Kaplan-Meier method. Results: The most common symptoms were cough (47.5%), dyspnea (45.6%), pain (27.3%), and weight loss (25.7%). Among all patients, 16% were asymptomatic. We demonstrated the negative prognostic significance of increasing number of lung cancer symptoms, that was significant after adjustment for age, TNM stages, and performance status, and morphological types of the cancer. Conclusion: Monitoring the severity and type of symptoms in patients with lung cancer can help in the diagnostics of the disease and the estimation of prognosis.

Disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic in March-October 2020: An exploratory analysis.

We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2 during the early phases of the pandemic in March-October 2020. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and multiple markers on daily resolution. Patients in the dataset were treated with hydroxychloroquine (N = 108), azithromycin (N = 72), favipiravir (N = 9), convalescent plasma (N = 7), dexamethasone (N = 4) and remdesivir (N = 3), often in combination. To explore association between treatments and patient outcomes we performed multiverse analysis, observing how the conclusions change between defensible choices of statistical model, predictors included in the model and other analytical degrees of freedom. Weak evidence to constrain the potential efficacy of azithromycin and favipiravir can be extracted from the data. Additionally, we performed external validation of several proposed prognostic models for Covid-19 severity showing that they mostly perform unsatisfactorily on our dataset.

Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils' but Impaired Monocytes' and Dendritic Cells' Responsiveness.

COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host-pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.

Complex Immunometabolic Profiling Reveals the Activation of Cellular Immunity and Biliary Lesions in Patients with Severe COVID-19.

This study aimed to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients that are associated with mild, moderate, severe, and fatal courses of the disease, and through a longitudinal follow-up, to understand the dynamics of the COVID-19 pathophysiology. All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. A severe course of COVID-19 was associated with an elevation of proinflammatory markers; an efflux of immature granulocytes into peripheral blood; the activation of CD8 T cells, which infiltrated the lungs; transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with a severe form of the disease. In contrast, patients with a fatal course of COVID-19 failed to upregulate markers of inflammation, showed discoordination of the immune response, and progressed toward acute kidney failure. COVID-19 is a disease with a multi-organ affinity that is characterized by the activation of innate and cellular adaptive immunity. Biliary lesions with an elevation of GGT and the organ infiltration of interleukin 6 (IL-6)-producing cells are the defining characteristics for patients with the fulminant disease.

Exacerbations of chronic obstructive pulmonary disease: An analysis of the care process in a regional hospital emergency department.

To describe the characteristics of patients visiting a Hospital Emergency Department (HED) due to chronic obstructive pulmonary disease (COPD) exacerbation (AECOPD) and to evaluate their management.A cross-sectional study of the first 219 patients with AECOPD visiting the HED of the University Hospital Arnau de Vilanova, Lleida, Spain, was performed from January to May 2016. The data collected included the following: main patient characteristics, diagnostic tests, applied treatments, response times, discharge destination, need for hospital admission, and re-admissions and deaths at 90 days. Comparisons were made according to sex and need for hospitalization.The patients consisted of 84% men, with a mean age (standard deviation [SD]) of 75.9 (11) years and a FEV1/FVC of 56 (13)%; 63% were ex-smokers. The median time (P25-P75) in the HED was 6 (4-10) hours, with shorter waiting times for severe patients. Additionally, 74% of patients required hospital admission. The percentages of re-admissions and mortality at 90 days were 25% and 14%, respectively. Among female patients, 63% never consumed tobacco, and the most frequent clinical phenotype was asthma combined with COPD; female patients visited the family doctor sooner after AECOPD than men (4 vs 7 days). Overall, the following areas of improvement were identified: use of sputum culture (performed in 3% of patients); documentation of variables; patient care times; and reduction in the time until first medical check-up.The overall quality of care provided to AECOPD patients was satisfactory and consistent with current clinical guidelines. Nevertheless, improving the quality of care at the HED requires establishing protocols that ensure that the necessary diagnostic tests are performed, optimize response times and guarantee that all relevant information is collected.

Respuesta: Exacerbación de la enfermedad pulmonar obstructiva crónica: ¿Se ha mejorado en la actitud terapéutica y en la decisión de ingreso? / Reply: Exacerbation of chronic obstructive pulmonary disease: is there an improvement of the therapeutic attitude and admission decision?

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Hospital de día de enfermedades respiratorias: impacto sobre la tasa de ingresos hospitalarios por exacerbaciones de la enfermedad pulmonar obstructiva crónica / Respiratory day hospital: Impact on the rate of hospital admissions due to chronic obstructive pulmonary disease exacerbations

Fundamento y objetivo: Las exacerbaciones de la enfermedad pulmonar obstructiva crónica (EA-EPOC) constituyen un factor determinante en el deterioro de los pacientes, con gran repercusión sobre el gasto sanitario. El objetivo de este estudio fue evaluar el impacto de la atención de las EA-EPOC en un hospital de día de enfermedades respiratorias (HDER) sobre la tasa de ingresos hospitalarios. Pacientes y método:Durante 14 meses se recogieron prospectivamente todos los episodios de EA-EPOC atendidos en el HDER y en el Servicio de Urgencias, excluyendo a los pacientes con otra causa de agudización o necesidad de ventilación mecánica invasiva.Resultados: Se incluyeron 226 episodios (173 pacientes, edad media [DE] de 72 [8] años). En el HDER se atendieron 121 (53,5%). El número de ingresos en el grupo del HDER fue claramente inferior (32,2 frente a 66,7%, p<0,001), incluso en pacientes con más ingresos el año previo. No hubo diferencias en la gravedad de la exacerbación ni en la tasa de reingresos ni de mortalidad en el seguimiento.Conclusiones: El manejo de las EA-EPOC en el HDER parece reducir el número de ingresos hospitalarios en comparación con un Servicio de Urgencias (AU)

Background and objective: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are considered to be the most important factor in determining the course of the disease, and have great impact on the health care system. We evaluated the effects of a Respiratory Day Hospital (RDH) on the rate of hospital admissions due to AE-COPD. Patients and methods:During 14 months, every case of AE-COPD seen at the RDH and emergency services was recruited prospectively. Patients were excluded when another known cause of exacerbation was present and/or when they required invasive mechanical ventilation. Results:226 episodes (173 patients) were included (72, SD 8years old). One hundred and twenty one cases received treatment at the RDH (53.5%). Admissions from the RDH group were noticeably lower (32.2 vs. 66.7%, p<0.001), even in patients with more admissions due to AE-COPD the year before the study. There were no differences either in terms of AE-COPD severity or in readmissions and mortality rates during the follow up.Conclusions: Management of AE-COPD in a RDH seems to be associated with a lower rate of hospital admissions in comparison with an emergency department (AU)

[Respiratory day hospital: Impact on the rate of hospital admissions due to chronic obstructive pulmonary disease exacerbations]. / Hospital de día de enfermedades respiratorias: impacto sobre la tasa de ingresos hospitalarios por exacerbaciones de la enfermedad pulmonar obstructiva crónica.

BACKGROUND AND OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are considered to be the most important factor in determining the course of the disease, and have great impact on the health care system. We evaluated the effects of a Respiratory Day Hospital (RDH) on the rate of hospital admissions due to AE-COPD. PATIENTS AND METHODS: During 14 months, every case of AE-COPD seen at the RDH and emergency services was recruited prospectively. Patients were excluded when another known cause of exacerbation was present and/or when they required invasive mechanical ventilation. RESULTS: 226 episodes (173 patients) were included (72, SD 8 years old). One hundred and twenty one cases received treatment at the RDH (53.5%). Admissions from the RDH group were noticeably lower (32.2 vs. 66.7%, p<0.001), even in patients with more admissions due to AE-COPD the year before the study. There were no differences either in terms of AE-COPD severity or in readmissions and mortality rates during the follow up. CONCLUSIONS: Management of AE-COPD in a RDH seems to be associated with a lower rate of hospital admissions in comparison with an emergency department.

Biot's breathing in a woman with fatal familial insomnia: is there a role for noninvasive ventilation?

We present the case of a 48-year-old woman suffering from fatal familial insomnia (FFI)--a rare prion disease--who developed Biot's breathing and secondary respiratory failure during the early stages of the illness. Once hypercapnia was detected a trial of nocturnal noninvasive ventilation (NIV) was offered with important improvement of arterial blood gases (ABG), and subjective good quality of sleep. To our knowledge, this is the first report in the medical literature of the use of NIV in the management approach of this devastating disease. Its impact on the prognosis and survival of these patients, however, is yet to be elucidated.