Increased incidence of Mycoplasma pneumoniae infections and hospital admissions in the Netherlands, November to December 2023.

Mycoplasma pneumoniae is an important cause of pneumonia and extra-pulmonary manifestations. We observed a rise in admissions due to M. pneumoniae infections starting October 2023 in a regional hospital in the Netherlands and an increased incidence in national surveillance data. The incidence in the Netherlands has not been that high since 2011. The patients had a lower median age compared with 2019 and 2020 (28 vs 40 years). M. pneumoniae should be considered in patients with respiratory symptoms, especially children.

Exotic viral hepatitis: A review on epidemiology, pathogenesis, and treatment.

Certain "exotic" viruses are known to cause clinical diseases with potential liver involvement. These include viruses, beyond regular hepatotropic viruses (hepatitis A, -B(D), -C, -E, cytomegalovirus, Epstein-Barr virus), that can be found in (sub)tropical areas and can cause "exotic viral hepatitis". Transmission routes typically involve arthropods (Crimean Congo haemorrhagic fever, dengue, Rift Valley fever, yellow fever). However, some of these viruses are transmitted by the aerosolised excreta of rodents (Hantavirus, Lassa fever), or via direct contact or contact with bodily fluids (Ebola). Although some exotic viruses are associated with high fatality rates, such as Ebola for example, the clinical presentation of most exotic viruses can range from mild flu-like symptoms, in most cases, right through to being potentially fatal. A smaller percentage of people develop severe disease with haemorrhagic fever, possibly with (fulminant) hepatitis. Liver involvement is often caused by direct tropism for hepatocytes and Kupffer cells, resulting in virus-mediated and/or immune-mediated necrosis. In all exotic hepatitis viruses, PCR is the most sensitive diagnostic method. The determination of IgM/IgG antibodies is a reasonable alternative, but cross-reactivity can be a problem in the case of flaviviruses. Licenced vaccines are available for yellow fever and Ebola, and they are currently under development for dengue. Therapy for exotic viral hepatitis is predominantly supportive. To ensure that preventive measures can be introduced to control possible outbreaks, the timely detection of these viruses is very important.

Interferon-α2 Auto-antibodies in Convalescent Plasma Therapy for COVID-19.

PURPOSE: To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment. METHODS: Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus-based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion. RESULTS: IFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract. CONCLUSIONS: IFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.

Predictors of poor haematopoietic stem cell mobilisation in patients with haematological malignancies at a South African centre.

BACKGROUND: Autologous stem cell transplant (ASCT) is an established consolidation strategy in the treatment of haematological malignancies, however poor mobilisation (PM) can contribute to patient morbidity and high resource utilisation. Identifying the incidence, risk factors for PM and engraftment outcomes are important goals in our resource limited setting. METHODS: We retrospectively analyzed patients with haematological malignancies that consecutively underwent ASCT at Groote Schuur hospital, Cape Town, South Africa from January 2013 to January 2019. RESULTS: 146 patients - majority with multiple myeloma (MM)(41,8%), F:M= 1:2, underwent leukapheresis with median age of 32 years (range, 9 - 66 years). PM occurred in 25/146 (17%), mobilisation failure (MF) in 3/146 (2%) and super mobilisation (SMs) in 99/146 (68%), respectively. Risk factors for PM were: diagnosis of acute leukaemia (RR = 25, 95% CI 3.4 - 183, p = 0.002) and Hodgkin lymphoma (RR = 19, 95% CI 2.6 - 142, p = 0.004); low white cell count (WCC) at harvest (WCC < 9 × 109/L (RR=4.3, 95% CI 2.3 - 8.3, p < 0.0001) and two vs one line of prior therapy (RR = 3.1, 95% CI 1.45 - 6.7, p = 0.0037). Median days to neutrophil and platelet engraftment were 14 days (95% CI 14-15 days) and 16 days (95% CI 15-16 days) respectively. CONCLUSION: PM occurred in 17% of a contemporary South African ASCT cohort, albeit with a low MF rate (2%). There was surprisingly high rate (68%) of SMs, possibly reflective of superfluous mobilisation strategy in MM patients. We identified predictive factors for PM that will lead to enhanced cost-effective use of plerixafor.

Specific Disease Knowledge as Predictor of Susceptibility to Availability Bias in Diagnostic Reasoning: a Randomized Controlled Experiment.

BACKGROUND: Bias in reasoning rather than knowledge gaps has been identified as the origin of most diagnostic errors. However, the role of knowledge in counteracting bias is unclear. OBJECTIVE: To examine whether knowledge of discriminating features (findings that discriminate between look-alike diseases) predicts susceptibility to bias. DESIGN: Three-phase randomized experiment. Phase 1 (bias-inducing): Participants were exposed to a set of clinical cases (either hepatitis-IBD or AMI-encephalopathy). Phase 2 (diagnosis): All participants diagnosed the same cases; 4 resembled hepatitis-IBD, 4 AMI-encephalopathy (but all with different diagnoses). Availability bias was expected in the 4 cases similar to those encountered in phase 1. Phase 3 (knowledge evaluation): For each disease, participants decided (max. 2 s) which of 24 findings was associated with the disease. Accuracy of decisions on discriminating features, taken as a measure of knowledge, was expected to predict susceptibility to bias. PARTICIPANTS: Internal medicine residents at Erasmus MC, Netherlands. MAIN MEASURES: The frequency with which higher-knowledge and lower-knowledge physicians gave biased diagnoses based on phase 1 exposure (range 0-4). Time to diagnose was also measured. KEY RESULTS: Sixty-two physicians participated. Higher-knowledge physicians yielded to availability bias less often than lower-knowledge physicians (0.35 vs 0.97; p = 0.001; difference, 0.62 [95% CI, 0.28-0.95]). Whereas lower-knowledge physicians tended to make more of these errors on subjected-to-bias than on not-subjected-to-bias cases (p = 0.06; difference, 0.35 [CI, - 0.02-0.73]), higher-knowledge physicians resisted the bias (p = 0.28). Both groups spent more time to diagnose subjected-to-bias than not-subjected-to-bias cases (p = 0.04), without differences between groups. CONCLUSIONS: Knowledge of features that discriminate between look-alike diseases reduced susceptibility to bias in a simulated setting. Reflecting further may be required to overcome bias, but succeeding depends on having the appropriate knowledge. Future research should examine whether the findings apply to real practice and to more experienced physicians.

Empowering Dutch and Surinamese children to prevent viral infections: implications from an international education module.

Viral infections have a large share in human morbidity and mortality. Next to vaccinations and hygiene measures, health education plays a role in preventing infections. Social scientists argue that empowerment should be included in health education, as increasing knowledge is insufficient to achieve sustainable behaviour change. Within the international education module 'Viruskenner', primary school students learn how to prevent virus infections by identifying health risks and developing interventions. This qualitative formative study explored to what extent Viruskenner creates conditions in which empowerment processes can arise and take place in the Netherlands and Suriname. Indicators of empowerment, as defined in the literature and placed in the attitude, social influence, and self-efficacy model, were assessed during semi-structured interviews (n = 24) with students, parents, teachers and facilitators. We conclude that Viruskenner is successful in creating conditions for empowerment processes to arise and take place, specifically in attitude and self-efficacy. According to interviewees, the module raised students' motivation, skills and confidence to take action to improve health behaviour. Educators played a stimulating role in the participatory setting in both countries, while content relevance and community involvement differed between the Netherlands and Suriname. These outcomes could improve this module and possibly other health education programmes.

Circulating Extracellular Vesicle Tissue Factor Activity During Orthohantavirus Infection Is Associated With Intravascular Coagulation.

BACKGROUND: Puumala orthohantavirus (PUUV) causes hemorrhagic fever with renal syndrome (HFRS). Patients with HFRS have an activated coagulation system with increased risk of disseminated intravascular coagulation (DIC) and venous thromboembolism (VTE). The aim of the study was to determine whether circulating extracellular vesicle tissue factor (EVTF) activity levels associates with DIC and VTE (grouped as intravascular coagulation) in HFRS patients. METHODS: Longitudinal samples were collected from 88 HFRS patients. Patients were stratified into groups of those with intravascular coagulation (n = 27) and those who did not (n = 61). We measured levels of circulating EVTF activity, fibrinogen, activated partial prothrombin time, D-dimer, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), and platelets. RESULTS: Plasma EVTF activity was transiently increased during HFRS. Levels of EVTF activity were significantly associated with plasma tPA and PAI-1, suggesting that endothelial cells could be a potential source. Patients with intravascular coagulation had significantly higher peak EVTF activity levels compared with those who did not, even after adjustment for sex and age. The peak EVTF activity value predicting intravascular coagulation was 0.51 ng/L with 63% sensitivity and 61% specificity with area under the curve = 0.63 (95% confidence interval, 0.51-0.76) and P = .046. CONCLUSIONS: Plasma EVTF activity during HFRS is associated with intravascular coagulation.

Leukocyte toll-like receptor expression in pathergy positive and negative Behçet's disease patients.

OBJECTIVES: To investigate whether the auto-inflammatory nature and the pathergic reaction in Behçet's disease (BD) are driven by a disturbed toll-like receptor (TLR) response. METHODS: We compared both TLR expression by flow-cytometry and TLR response by stimulation assay in 18 BD patients (both pathergy positive and pathergy negative) with 15 healthy controls. RESULTS: Expression of TLR1 and 2 was significantly elevated in B-lymphocytes of BD patients compared with healthy controls. TLR1, 2 and 4 were significantly more highly expressed in both CD4+ and CD8+ T-lymphocytes of BD patients. Granulocytes of BD patients displayed significantly higher expression of TLR1, 2, 4 and 6. TLR2, 4 and 5 expression was significantly increased on classical monocytes of BD patients. Intermediate monocytes of BD patients showed an increase in expression of TLR2. Furthermore, TLR2 and 5 were significantly more highly expressed in non-classical monocytes of BD patients. In pathergy positive patients, TLR5 was even more highly expressed compared with pathergy negative patients on B- and T-lymphocytes and granulocytes. Furthermore, TLR2 and 5 showed an elevated TNF-α response to stimulation with their cognate ligands. CONCLUSION: Immune cells of BD patients overexpress TLR1, 2, 4, 5 and 6. Furthermore, after stimulation of TLR2 and 5, BD patients demonstrate a more potent TNF-α response. Although this is a small cohort, in the pathergy positive patients, TLR5 expression is even further augmented, suggesting that a microbial (flagellin) or damage (HMGB1) associated signal may trigger the exaggerated immune response that is characteristic for the pathergy phenomenon in BD. In conclusion, these results point to an exaggerated TLR response in the auto-inflammatory nature of BD.

Point-of-care thrombocyte function testing using multiple-electrode aggregometry in dengue patients: an explorative study.

BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.

Endemic and emerging acute virus infections in Indonesia: an overview of the past decade and implications for the future.

Being the largest archipelago country in the world, with a tropical climate and a unique flora and fauna, Indonesia habitats one of the most diverse biome in the world. These characteristics make Indonesia a popular travel destination, with tourism numbers increasing yearly. These characteristics also facilitate the transmission of zoonosis and provide ideal living and breading circumstances for arthropods, known vectors for viral diseases. A review of the past 10 years of literature, reports of the Ministry of Health, Republic of Indonesia and ProMED-mail shows a significant increase in dengue infection incidence. Furthermore, chikungunya, Japanese encephalitis and rabies are proven to be endemic in Indonesia. The combination of cohort studies, governmental data and ProMED-mail reveals an integrated overview for those working in travel medicine and public health, focusing on both endemic and emerging acute virus infections. This review summarizes the epidemiology of acute virus infections in Indonesia, including outbreak reports, as well as public health response measurements and their potential or efficacy. Knowledge about human behaviour, animal reservoirs, climate factors, environment and their role in emerging virus infection are discussed. We aim to support public health authorities and health care policy makers in a One Health approach.

Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions.

A major cause of respiratory failure during influenza A virus (IAV) infection is damage to the epithelial-endothelial barrier of the pulmonary alveolus. Damage to this barrier results in flooding of the alveolar lumen with proteinaceous oedema fluid, erythrocytes and inflammatory cells. To date, the exact roles of pulmonary epithelial and endothelial cells in this process remain unclear.Here, we used an in vitro co-culture model to understand how IAV damages the pulmonary epithelial-endothelial barrier. Human epithelial cells were seeded on the upper half of a transwell membrane while human endothelial cells were seeded on the lower half. These cells were then grown in co-culture and IAV was added to the upper chamber.We showed that the addition of IAV (H1N1 and H5N1 subtypes) resulted in significant barrier damage. Interestingly, we found that, while endothelial cells mounted a pro-inflammatory/pro-coagulant response to a viral infection in the adjacent epithelial cells, damage to the alveolar epithelial-endothelial barrier occurred independently of endothelial cells. Rather, barrier damage was associated with disruption of tight junctions amongst epithelial cells, and specifically with loss of tight junction protein claudin-4.Taken together, these data suggest that maintaining epithelial cell integrity is key in reducing pulmonary oedema during IAV infection.

Activation of coagulation and tissue fibrin deposition in experimental influenza in ferrets.

BACKGROUND: Epidemiological studies relate influenza infection with vascular diseases like myocardial infarction. The hypothesis that influenza infection has procoagulant effects on humans has been investigated by experimental animal models. However, these studies often made use of animal models only susceptible to adapted influenza viruses (mouse adapted influenza strains) or remained inconclusive. Therefore, we decided to study the influence of infection with human influenza virus isolates on coagulation in the well-established ferret influenza model. RESULTS: After infection with either a seasonal-, pandemic- or highly pathogenic avian influenza (HPAI-H5N1) virus strain infected animals showed alterations in hemostasis compared to the control animals. Specifically on day 4 post infection, a four second rise in both PT and aPTT was observed. D-dimer concentrations increased in all 3 influenza groups with the highest concentrations in the pandemic influenza group. Von Willebrand factor activity levels increased early in infection suggesting endothelial cell activation. Mean thrombin-antithrombin complex levels increased in both pandemic and HPAI-H5N1 virus infected ferrets. At tissue level, fibrin staining showed intracapillary fibrin deposition especially in HPAI-H5N1 virus infected ferrets. CONCLUSION: This study showed hemostatic alterations both at the circulatory and at the tissue level upon infection with different influenza viruses in an animal model closely mimicking human influenza virus infection. Alterations largely correlated with the severity of the respective influenza virus infections.

Controlled Mechanical Ventilation in Critically Ill Patients and the Potential Role of Venous Bagging in Acute Kidney Injury.

A very low incidence of acute kidney injury (AKI) has been observed in COVID-19 patients purposefully treated with early pressure support ventilation (PSV) compared to those receiving mainly controlled ventilation. The prevention of subdiaphragmatic venous congestion through limited fluid intake and the lowering of intrathoracic pressure is a possible and attractive explanation for this observed phenomenon. Both venous congestion, or "venous bagging", and a positive fluid balance correlate with the occurrence of AKI. The impact of PSV on venous return, in addition to the effects of limiting intravenous fluids, may, at least in part, explain this even more clearly when there is no primary kidney disease or the presence of nephrotoxins. Optimizing the patient-ventilator interaction in PSV is challenging, in part because of the need for the ongoing titration of sedatives and opioids. The known benefits include improved ventilation/perfusion matching and reduced ventilator time. Furthermore, conservative fluid management positively influences cognitive and psychiatric morbidities in ICU patients and survivors. Here, it is hypothesized that cranial lymphatic congestion in relation to a more positive intrathoracic pressure, i.e., in patients predominantly treated with controlled mechanical ventilation (CMV), is a contributing risk factor for ICU delirium. No studies have addressed the question of how PSV can limit AKI, nor are there studies providing high-level evidence relating controlled mechanical ventilation to AKI. For this perspective article, we discuss studies in the literature demonstrating the effects of venous congestion leading to AKI. We aim to shed light on early PSV as a preventive measure, especially for the development of AKI and ICU delirium and emphasize the need for further research in this domain.

Role of knowledge and reasoning processes as predictors of resident physicians' susceptibility to anchoring bias in diagnostic reasoning: a randomised controlled experiment.

BACKGROUND: Diagnostic errors have been attributed to reasoning flaws caused by cognitive biases. While experiments have shown bias to cause errors, physicians of similar expertise differed in susceptibility to bias. Resisting bias is often said to depend on engaging analytical reasoning, disregarding the influence of knowledge. We examined the role of knowledge and reasoning mode, indicated by diagnosis time and confidence, as predictors of susceptibility to anchoring bias. Anchoring bias occurs when physicians stick to an incorrect diagnosis triggered by early salient distracting features (SDF) despite subsequent conflicting information. METHODS: Sixty-eight internal medicine residents from two Dutch university hospitals participated in a two-phase experiment. Phase 1: assessment of knowledge of discriminating features (ie, clinical findings that discriminate between lookalike diseases) for six diseases. Phase 2 (1 week later): diagnosis of six cases of these diseases. Each case had two versions differing exclusively in the presence/absence of SDF. Each participant diagnosed three cases with SDF (SDF+) and three without (SDF-). Participants were randomly allocated to case versions. Based on phase 1 assessment, participants were split into higher knowledge or lower knowledge groups. MAIN OUTCOME MEASUREMENTS: frequency of diagnoses associated with SDF; time to diagnose; and confidence in diagnosis. RESULTS: While both knowledge groups performed similarly on SDF- cases, higher knowledge physicians succumbed to anchoring bias less frequently than their lower knowledge counterparts on SDF+ cases (p=0.02). Overall, physicians spent more time (p<0.001) and had lower confidence (p=0.02) on SDF+ than SDF- cases (p<0.001). However, when diagnosing SDF+ cases, the groups did not differ in time (p=0.88) nor in confidence (p=0.96). CONCLUSIONS: Physicians apparently adopted a more analytical reasoning approach when presented with distracting features, indicated by increased time and lower confidence, trying to combat bias. Yet, extended deliberation alone did not explain the observed performance differences between knowledge groups. Success in mitigating anchoring bias was primarily predicted by knowledge of discriminating features of diagnoses.

A Systematic Review of the Pulmonary Microbiome in Patients with Acute Exacerbation COPD Requiring ICU Admission.

Background: Chronic obstructive pulmonary disease (COPD) is a major health concern. Acute exacerbations (AECOPD) may require intensive care unit (ICU) admission and mechanical ventilation. Acute infections and chronic colonization of the respiratory system are known to precipitate AECOPD. Detailed knowledge of the respiratory microbiome could lead to effective treatment and prevention of exacerbations. Objective: The aim of this review is to summarize the available evidence on the respiratory microbiome of patients with a severe AECOPD requiring mechanical ventilation and intensive care admission. Methods: A systematic literature search was conducted to identify the published papers until January 2023. The collected data were then subjected to qualitative analysis. After the first analysis, a secondary focused review of the most recent publications studying the relationship between microbiome and mortality in AECOPD was performed. Results: Out of 120 screened articles six articles were included in this review. Potentially pathogenic microorganisms (PPMs) were identified in 30% to 72% of the patients with community-acquired bacteria, gram-negative enteric bacilli, Stenotrophomonas and Pseudomonas being the most frequently isolated. During hospitalization, 21% of patients experienced colonization by PPMs. Adequate antimicrobial therapy resulted in the eradication of 77% of the identified PPMs. However, 24% of the bacteria displayed multi-drug resistance leading to prolonged or failure of eradication. Conclusion: PPMs are prevalent in a significant proportion of patients experiencing an AECOPD. The most identified PPMs include community-acquired pathogens and gram-negative enteric bacilli. Notably, no differences in mortality or duration of ventilation were observed between patients with and without isolated PPMs. However, the included studies did not investigate the virome of the patients, which may influence the microbiome and the outcome of infection. Therefore, further research is essential to comprehensively investigate the complete microbial and viral composition of the lower respiratory system in COPD patients admitted to the ICU.

Rodent-borne hemorrhagic fevers: under-recognized, widely spread and preventable - epidemiology, diagnostics and treatment.

This review presents an overview of the most important rodent-borne hemorrhagic fever pathogens directly transmitted from rodents to humans, namely Leptospira and hantaviruses, together with the New- and Old-World arenaviruses. These zoonotic diseases frequently share clinical symptoms, transmission routes and other epidemiological features and often have an emerging pattern. Differential diagnostics could benefit from a syndrome-based approach grouping these pathogens. In this review extensive descriptions of the epidemiology, clinical symptoms, diagnostics and treatment are provided including a practical overview, listing clinical features, diagnostics and risk factors for each selected rodent-borne hemorrhagic fever pathogen.

Early Patient-Triggered Pressure Support Breathing in Mechanically Ventilated Patients with COVID-19 May Be Associated with Lower Rates of Acute Kidney Injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) in COVID-19 patients often necessitates mechanical ventilation. Although much has been written regarding intensive care admission and treatment for COVID-19, evidence on specific ventilation strategies for ARDS is limited. Support mode during invasive mechanical ventilation offers potential benefits such as conserving diaphragmatic motility, sidestepping the negative consequences of the longer usage of neuromuscular blockers, and limiting the occurrence of ventilator-induced lung injury (VILI). METHODS: In this retrospective cohort study of mechanically ventilated and confirmed non-hyperdynamic SARS-CoV-2 patients, we studied the relation between the occurrence of kidney injury and the decreased ratio of support to controlled ventilation. RESULTS: Total AKI incidence in this cohort was low (5/41). In total, 16 of 41 patients underwent patient-triggered pressure support breathing at least 80% of the time. In this group we observed a lower percentage of AKI (0/16 vs. 5/25), determined as a creatinine level above 177 µmol/L in the first 200 h. There was a negative correlation between time spent on support ventilation and peak creatinine levels (r = -0.35 (-0.6-0.1)). The group predominantly on control ventilation showed significantly higher disease severity scores. CONCLUSIONS: Early patient-triggered ventilation in patients with COVID-19 may be associated with lower rates of acute kidney injury.

Influenza: seasonality and travel-related considerations.

RATIONALE FOR REVIEW: This review aims to summarize the transmission patterns of influenza, its seasonality in different parts of the globe, air travel- and cruise ship-related influenza infections and interventions to reduce transmission. KEY FINDINGS: The seasonality of influenza varies globally, with peak periods occurring mainly between October and April in the northern hemisphere (NH) and between April and October in the southern hemisphere (SH) in temperate climate zones. However, influenza seasonality is significantly more variable in the tropics. Influenza is one of the most common travel-related, vaccine-preventable diseases and can be contracted during travel, such as during a cruise or through air travel. Additionally, travellers can come into contact with people from regions with ongoing influenza transmission. Current influenza immunization schedules in the NH and SH leave individuals susceptible during their respective spring and summer months if they travel to the other hemisphere during that time. CONCLUSIONS/RECOMMENDATIONS: The differences in influenza seasonality between hemispheres have substantial implications for the effectiveness of influenza vaccination of travellers. Health care providers should be aware of influenza activity when patients report travel plans, and they should provide alerts and advise on prevention, diagnostic and treatment options. To mitigate the risk of travel-related influenza, interventions include antivirals for self-treatment (in combination with the use of rapid self-tests), extending the shelf life of influenza vaccines to enable immunization during the summer months for international travellers and allowing access to the influenza vaccine used in the opposite hemisphere as a travel-related vaccine. With the currently available vaccines, the most important preventive measure involves optimizing the seasonal influenza vaccination. It is also imperative that influenza is recognized as a travel-related illness among both travellers and health care professionals.

Levels of Fibrinogen Variants Are Altered in Severe COVID-19.

Background Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk. Aim To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. Methods In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (α E ), and γ' fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Results Healthy controls and ward patients with COVID-19 ( n = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did ( n = 19) or did not develop thrombosis ( n = 18) and ICU patients with pneumococcal infection ( n = 6) had higher absolute levels of functional, total, intact, and α E fibrinogen than healthy controls ( n = 7). The relative α E fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ' fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Conclusion Our results show that severe COVID-19 is associated with increased levels of α E fibrinogen and decreased relative levels of γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.

Serum Markers Associated with Disease Severity in a Bosnian Hemorrhagic Fever with Renal Syndrome Cohort.

Puumala orthohantavirus (PUUV) is endemic in Europe and can cause hemorrhagic fever with renal syndrome (nephropathia epidemica). Disease features include fever, thrombocytopenia, and acute kidney injury (AKI). This retrospective cohort study of forty PUUV patients aims to characterize associations of serum immunological, hemostatic or kidney injury markers to disease severity. While interleukin-18 (IL-18) was significantly increased in severely thrombocytopenic patients (<100 × 109 platelets/L) compared to patients with higher platelet counts, RANTES was significantly decreased in these patients. These data suggest that patients with significant thrombocytopenia might have experienced pronounced Th1 immune responses. When kidney dysfunction was used as the primary disease outcome, recently identified AKI biomarkers (Cystatin C, insulin-like growth factor-binding protein 7, Nephrin, and trefoil factor 3) were significantly upregulated in patients with severe PUUV infection, defined as the estimated glomerular filtration rate (eGFR) below 30 m/min/1.73 m2. The increased expression of these markers specifically indicates pathology in glomeruli and proximal tubuli. Furthermore, E-selectin was significantly higher while interferon gamma-induced protein 10 (IP-10) was significantly lower in PUUV patients with more severe kidney dysfunction compared to patients with higher eGFR-values. Increased E-selectin illustrates the central role of endothelial cell activation, whereas decreased IP-10 could indicate a less important role of this cytokine in the pathogenesis of kidney dysfunction.