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BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI.METHODS: A total of 2,571 participants were prospectively enrolled in the Influenza vaccination after myocardial infarction (IAMI) trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in eight countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2,467 participants with ST-segment elevation MI (STEMI, n = 1,348) or non-ST-segment elevation MI (NSTEMI, n = 1,119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification.RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P = .237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at one year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P = .028).CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.

ObjectivesThe steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.DesignCross-sectional study.Setting and participantsPlasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measuresReceipt of invasive mechanical ventilation (IMV) and in-hospital mortality.ResultsVitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (ConclusionsVitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes.

Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host–pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.

Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.

Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak. Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children. From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic. In particular, children present significantly less fever, cough and pneumonia compared to adults. However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1. No vertical transmission of SARS-CoV-2 has been described so far.

Item does not contain fulltext Influenza virus infection is now recognised as a risk factor for invasive pulmonary aspergillosis (IPA). Delays in diagnosis contribute to delayed commencement of antifungal therapy. In addition, the emergence of resistance to first-line triazole antifungal agents puts emphasis on early detection to prevent adverse outcomes. We present 2 allogeneic stem cell transplant patients who developed IPA due to triazole-resistant Aspergillus fumigatus following influenza infection. We underline the challenges faced in the management of these cases, the importance of early diagnosis and need for surveillance given the emergence of triazole resistance.

We report an otherwise healthy 10-year-old boy who was brought to the emergency department with altered mental status, vomiting, diarrhoea and fever (39.5°C), without signs of meningitis. The CT scan revealed bilateral hypodensities of the thalamus and cerebellum, with diffuse oedema and slight compression of the brainstem and a triventricular hydrocephalus. Lumbar puncture and blood examination revealed markedly elevated protein level of 2.4 g/L in cerebrospinal fluid and high serum aminotransferase, characteristic of acute necrotising encephalopathy (ANE). The PCR of the nasopharyngeal swab was influenza A positive. Because of signs of high intracranial pressure, mannitol was given, an external ventricular drain was placed and subsequently, a posterior fossa craniectomy was performed. Postoperatively, he showed signs of cerebellar mutism with emotional instability and diminished speech. Six months after presentation, he showed full recovery. This case illustrates ANE as a rare complication of influenza A infection.

Background: Guideline-concordant therapies have been proven to be associated with improved health and economic outcomes in the treatment of community-acquired pneumonia (CAP). However, actual use of CAP guidelines remains poor, but using tailored interventions looks promising. Based on local observations, we assessed the impact of low-intensity interventions to improve guideline use.Methods: Pre- and post-intervention study with segmented regression analysis in a large tertiary care centre [University Hospitals Leuven (UZL)] and a smaller secondary care control hospital [Ziekenhuis Oost-Limburg (ZOL)] from October 2007 through to June 2010 in Belgium.Results: A total of 477 patients were included in UZL, with 58.5% of the patients treated according to local guidelines. Guideline adherence remained stable, but a decrease (-28.6%; P=0.021) was observed during guideline re-introduction in October 2009. Further analysis showed a high correlation with the concurrent A/H1N1 influenza pandemic (r(point-biserial)=0.683; P=0.045) and with suspected influenza infection (odds ratio=2.70; P=0.038). In ZOL, 326 patients were enrolled, with 69.3% being treated concordantly. A similar, non-significant decrease in guideline adherence was observed after October 2009.Conclusions: Our interventions did not lead to a higher proportion of CAP patients receiving guideline-compliant therapy. Instead, a compliance decrease was observed, coinciding with the peak in the A/H1N1 pandemic in the population. Similar observations could be made in ZOL. The widespread attention for this pandemic may have altered the perception of needed antibiotic therapy for pulmonary infections, bypassing our interventions and decreasing actual guideline compliance. Increased vigilance and follow-up is needed when epidemics with similar impact occur in the future.

Pneumonia is one of the leading causes of death in the elderly. Streptococcus pneumoniae is the leading etiological agent, but the identification of a pathogen remains infrequent despite advances in microbiological methods. Antibiotic resistant organisms should be considered as potential causal agents in recently hospitalized patients and patients with recent antibiotic exposure and influenza during the flu season. The clinical diagnosis is difficult due to frequent atypical presentation. Prognostic scores are not always appropriate to predict the need for hospitalization in very old patients. Studies on the role of low-dose chest CT for the diagnosis, management and prevention should help improve the management of this disease in the future.

Objetivo: describir las características clínicas de los casos de gripe pandémica A (H1N1) 2009 diagnosticados por pediatras centinela del programa PIDIRAC (Programa de información diaria de las infecciones respiratorias agudas de Catalunya) en atención primaria (AP). Material y métodos: la muestra de estudio estaba formada por los casos visitados por cuatro de los pediatras centinela que participan en el programa PIDIRAC. Se recogieron de forma sistemática, para evitar sesgo de muestreo, muestras faríngeas y nasales de los casos sospechosos de gripe para su estudio virológico. Cada semana del periodo de estudio se seleccionaron los dos primeros pacientes que acudieron a la consulta y cumplían con los criterios de caso sospechoso, se recogieron sus datos demográficos y clínicos y se cursó el estudio viral. A los 55 niños con gripe pandémica A (H1N1) 2009 se les realizó un seguimiento telefónico para conocer la evolución del cuadro. Resultados: la mayor parte de los casos tenían una edad entre cinco y 14 años (89,1%; intervalo de confianza del 95% [IC 95%]: 77,8-95,9). Los síntomas más frecuentes fueron la fiebre (criterio de inclusión), que duró una media de 3,6 días (desviación estándar [DE]: 1,6) y la tos. Más de la mitad refirieron también odinofagia, rinitis o cefalea. En general, el cuadro clínico fue leve, aunque un niño fue ingresado durante 48 horas por presentar una neumonía. De los 13 niños que tenían antecedentes de asma, dos presentaron exacerbaciones leves. Ningún niño recibió tratamiento antiviral. Conclusión: a pesar de los temores iniciales, los casos de gripe pandémica A (H1N1) 2009 en los niños atendidos en nuestras consultas de AP han sido generalmente leves. Objective: to describe the clinical features of pandemic influenza cases diagnosed in primary health care by sentinel pediatricians who participate in the PIDIRAC surveillance scheme (Programa de información diaria de las infecciones respiratorias agudas de Catalunya). Methods: study sample included the cases of confirmed influenza A (H1N1) 2009 attended by sentinel pediatricians that collaborate with PIDIRAC. Pharyngeal and nasopharyngeal swabs for virologic analysis of suspected influenza cases were collected on a systematic basis in order to avoid bias. Every week during the study period the first two patients that consult and comply with the definition of suspicious case of influenza were recruited, if consent was obtained. Demographic characteristics and clinical features were recorded, and virologic studies were performed. The fifty-five children with confirmed pandemic influenza A (H1N1) 2009 were contacted by telephone in order to obtain information regarding their clinical status. Results: most of the cases were 5-14 years old children and adolescents (89.1%, 95% CI 77.8-95.9). The most frequent symptoms were fever (inclusion criteria), that lasted a mean of 3.6 days (SD = 1.6) and cough. More than 50% of patients also presented with sore throw, rhinitis or headache. In general, the disease was mild even though one child was hospitalised during 48 hours because he (or she) had a pneumonia. Of the thirteen patients who suffered from asthma only two had mild exacerbations. None of the patients needed antiviral treatment. Conclusions: despite initial fears, the cases of pandemic influenza A (H1N1) 2009 treated in our community health centres have been generally mild.

'Acute respiratory distress syndrome' (ARDS) developed as a serious complication of an infection with the influenza virus A (H1N1) ('swine flu') in 3 children: a 15-year-old girl, a 6-year-old boy and a 14-year-old girl. The latter two patients also suffered from septic shock. Intensive ICU treatment, including mechanical ventilation, did not lead to recovery. The first two patients eventually recovered following treatment with extracorporeal membrane oxygenation (ECMO), but the third patient's condition was too unstable for transfer to an ECMO centre. This patient died.

Dear Editor, After traumatic freshwater submersion, severe respiratory failure and destructive lung injury are dreaded complications [1]. If conventional treatment fails to provide adequate oxygenation, veno-venous extracorporeal membrane oxygenation (VV-ECMO) is the only remaining treatment modality [2]. Yet, in the presence of concomitant trauma, the need for anticoagulation in VV-ECMO poses a therapeutic dilemma [3]. Here, we report two trauma patients treated with mobile VV-ECMO after freshwater aspiration despite an increased trauma-related bleeding risk. A 33-year-old healthy male fell off a tilted wagon, lost consciousness, and suffered from freshwater submersion, resulting in brain and lung contusion, and an injury severity score (ISS) of 26. Despite lung-protective ventilation and prone position, respiratory failure progressed (Murray score 3.0 [4]) and VV-ECMO was initiated within 24 h after admission. The further clinical course was uneventful and no additional pulmonary complications occurred. Successful weaning from ECMO was accomplished on day 11, followed by intensive care unit (ICU) discharge on day 13. A 24-year-old healthy male experienced freshwater aspiration after a quad bike accident, resulting in bilateral brain contusion, lung contusion, rib fractures, bilateral pneumothoraces, and splenic rupture grade II/VI (ISS 29). On day 6, the respiratory condition deteriorated (Murray score 3.5 [4]), necessitating VV-ECMO. The subsequent clinical course was complicated by persistent pneumothoraces, multiple pulmonary abscesses, empyema, and parenchymal destruction (Fig. 1a–c), ultimately allowing successful weaning from VV-ECMO (day 54), mechanical ventilation (day 66) and ICU discharge (day 69). Fig. 1 Serial chest CT scans on day 34 (a), 46 (b), and 58 (c) of VV-ECMO support in the 24-year-old male showing gradual improvement of pulmonary injury. Mobile VV-ECMO equipment mounted on the transport trolley (d). Bi-caval dual lumen catheter (e) optimally ... In both patients, referral on mechanical ventilation from the primary hospital to a tertiary academic center was considered impossible because of respiratory instability. Therefore, our mobile team comprising two experienced senior intensivists, an ICU nurse, and a perfusionist initiated VV-ECMO off-center before transport (Prolonged Life Support, Maquet®, Fig. 1d). One intensivist introduced a 27-French bi-caval dual lumen catheter (Avalon Elite, Avalon Laboratories®, Fig. 1e) via the right internal jugular vein, resulting in a blood flow of 4 L/min. Optimal catheter positioning was guided echocardiographically by the second intensivist adhering to a protocolized combined transthoracic-transesophageal approach using our mobile equipment (Philips CX 50) (Fig. 1f) [5]. The use of a single insertion site minimized the risk of cannula displacement, introduction of site bleeding, and infection while facilitating patient handling. In both patients no VV-ECMO related complications occurred. Considering the bleeding risk due to concomitant multitrauma, therapeutic anticoagulation was undesirable [3]. Consequently, the first patient received a half-therapeutic dose of unfractionated heparin intravenously (5,000 IU bolus), the second acetylsalicylic acid (100 mg) orally (300 mg bolus). In the absence of hemorrhagic complications, both patients switched to a therapeutic dosage of unfractionated heparin 48 h after the start of VV-ECMO. Severe but potentially reversible pulmonary injury can successfully be treated with VV-ECMO in trauma-related freshwater submersion. The combined advantages of mobile, off-center VV-ECMO initiation using a bi-caval dual lumen catheter in trauma patients have, to the best of our knowledge, not been described before. As pointed out earlier, this approach should be considered as a valid therapeutic option in this category of patients despite the assumed increased bleeding risk associated with multitrauma.