Janesh Pillay

• MD, PhD
• Intensivist at University of Groningen

Neutrophils are essential effector cells of the innate immune response and are indispensable for host defense. Apart from their antimicrobial functions, neutrophils inform and shape subsequent immunity. This immune modulatory functionality might however be considered limited because of their generally accepted short lifespan (< 1 day). In contrast...

Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models of cancer, infectious disease, bone marrow transp...

Neutrophils are classically considered as cells pivotal for the first line of defense against invading pathogens. In recent years, evidence has accumulated that they are also important in the orchestration of adaptive immunity. Neutrophils rapidly migrate in high numbers to sites of inflammation (e.g., infection, tissue damage, and cancer) and are...

Severe influenza virus infection can lead to life-threatening pathology through immune-mediated tissue damage. In various experimental models, this damage is dependent on T-cells. There is conflicting evidence regarding the role of neutrophils in influenza-mediated pathology. Neutrophils are often regarded as cells causing tissue damage, but in rec...

Key Points Neutrophil subsets circulating during acute inflammation are characterized by differential bacterial containment capacity. Adequate antimicrobial containment is associated with profound phagosomal acidification yet independent of reactive oxygen species.

Acute respiratory distress syndrome (ARDS) is pathologically characterized by diffuse alveolar damage (DAD) and is associated with high morbidity and mortality rates. Remodeling of the extracellular matrix (ECM), which is pivotal for tissue repair and organ recovery, may play a large role in persistent ARDS. This study investigated the compositiona...

Purpose Some ICU patients remain critically ill despite reversal of the original admission diagnosis, driven by a cascade of events resulting in new and persistent organ failure. Secondary infections and systemic inflammation are important components of this cascade and may be visualised using [ ¹⁸ F]FDG PET/CT. The aim of this dual centre retrospe...

Background Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the...

Mitochondrial oxygen tension (MitoPO2) is a promising novel non-invasive bedside marker of circulatory shock and is associated with organ failure. The measurement of mitoPO2 requires the topical application of 5-aminolevulinc acid (ALA) to induce sufficient concentrations of the fluorescent protein protoporphyrin-IX within (epi)dermal cells. Curren...

Background Acute respiratory distress syndrome (ARDS) is pathologically characterized by diffuse alveolar damage (DAD) and is associated with high morbidity and mortality rates. Remodeling of the extracellular matrix (ECM), which is pivotal for both tissue repair and organ recovery, may play a large role in persistent ARDS. This study investigated...

Whereas urinary creatinine excretion (UCE) is an established marker of muscle mass, both in critically ill and non-critically ill patients, analysis of urinary urea excretion (UUE) may allow estimation of proteolysis that is associated with critical illness. We evaluated the time courses of plasma urea and creatinine as well UUE and UCE in critical...

Rationale In acute respiratory distress syndrome (ARDS), optimal timing of transition from controlled to assisted ventilation and the ventilatory parameters which define this are unknown. Premature transition may impair recovery of an injured lung through patient self-inflicted lung injury. Objectives To investigate whether the airway occlusion pre...

Introduction Administration of oxygen therapy is common, yet there is a lack of knowledge on its ability to prevent cellular hypoxia as well as on its potential toxicity. Consequently, the optimal oxygenation targets in clinical practice remain unresolved. The novel PpIX technique measures the mitochondrial oxygen tension in the skin (mitoPO 2 ) wh...

Background: Sepsis is associated with high morbidity and mortality, primarily due to systemic inflammation-induced tissue damage, resulting organ failure, and impaired recovery. Regulated extracellular matrix (ECM) turnover is crucial for maintaining tissue homeostasis in health and in response to disease-related changes in the tissue microenvironm...

The introduction of new long axial field of view (LAFOV) scanners is a major milestone in positron emission tomography/computed tomography (PET/CT) imaging. With these new systems a revolutionary reduction in scan time can be achieved, concurrently lowering tracer dose. Therefore, PET/CT has come within reach for groups of patients in whom PET/CT p...

Background Whereas urinary creatinine excretion (UCE) is an established marker of muscle mass, both in critically ill and non-critically ill patients, analysis of urinary urea excretion (UUE) may allow estimation of proteolysis that is associated with critical illness. We evaluated the time courses of plasma urea and creatinine as well UUE and UCE...

Background: Since most endocrine glands express ACE-2 receptors and can be infected by SARS-CoV-2 virus, this retrospective multicentre observational study aims to assess the metabolic activity of thyroid and adrenal glands of COVID-19 patients by 18F-FDG PET/CT. Methods: We retrospectively evaluated the 18F-FDG PET/CT scans of COVID-19 patients ad...

Background High-flow nasal oxygen (HFNO) is increasingly used in patients with acute hypoxemic respiratory failure. It is uncertain whether a broadened Berlin definition of acute respiratory distress syndrome (ARDS), in which ARDS can be diagnosed in patients who are not receiving ventilation, results in similar groups of patients receiving HFNO as...

Background: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in sept...

Background: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as s...

18F-FDG-PET/CT imaging has become a key tool to evaluate infectious and inflammatory diseases. However, application of 18F-FDG-PET/CT in patients in the intensive care unit (ICU) is limited, which is remarkable since the development of critical illness is closely linked to infection and inflammation. This limited use is caused by perceived complexi...

BACKGROUND In hospitalized COVID-19 patients dosing and timing of corticosteroids varies widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In the most sick patients, high-dose corticosteroids are often administered as salvage late...

Circulatory shock is the inadequacy to supply mitochondria with enough oxygen to sustain aerobic energy metabolism. A novel non-invasive bedside measurement was recently introduced to monitor the mitochondrial oxygen tension in the skin (mitoPO2). As the most downstream marker of oxygen balance in the skin, mitoPO2 may provide additional informatio...

Purpose We report the findings of four critically ill patients who underwent an [ ¹⁸ F]FDG-PET/CT because of persistent inflammation during the late phase of their COVID-19. Methods Four mechanically ventilated patients with COVID-19 were retrospectively discussed in a research group to evaluate the added value of [ ¹⁸ F]FDG-PET/CT. Results Altho...

Background Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 p...

Environmental insults including respiratory infections, in combination with genetic predisposition, may lead to lung diseases such as chronic obstructive pulmonary disease, lung fibrosis, asthma, and acute respiratory distress syndrome. Common characteristics of these diseases are infiltration and activation of inflammatory cells and abnormal extra...

Background The SpO2/FiO2 is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO2/FiO2 for mortality in patients with ARDS due to COVID–19. Methods This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID–19....

Background 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an advanced imaging technique that can be used to examine the whole body for an infection focus in a single examination in patients with bloodstream infection (BSI) of unknown origin. However, literature on the use of this technique in in...

Background The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory fa...

Introduction Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-re...

COVID-19 might lead to multi-organ failure and, in some cases, to death. The COVID-19 severity is associated with a “cytokine storm.” Danger-associated molecular patterns (DAMPs) are proinflammatory molecules that can activate pattern recognition receptors, such as toll-like receptors (TLRs). DAMPs and TLRs have not received much attention in COVID...

Background: There is uncertainty about how much positive end-expiratory pressure (PEEP) should be used in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). Objective: To investigate whether a higher PEEP strategy is superior to a lower PEEP strategy regarding the number of ventilator-free days (...

Abstract Background The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury. Methods This study involved histopa...

Introduction Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers (ARBs) are cornerstone treatments in several cardiovascular disease entities (1). The RAAS is a central regulator of blood pressure, consisting of two counterregulatory pathwa...

Background Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak. Methods PRoVENT-COVID is a national, multicentre, retros...

Treatment with the CXCR4 antagonist, plerixafor (AMD3100), has been proposed for clinical use in patients with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome and in pulmonary fibrosis. However, there is controversy with respect to the impact of plerixafor on neutrophil dynamics in the lung, which may affect its safety p...

Neutrophil antibacterial capacity is measured in animal models and in vitro as an important indicator of neutrophil function. To be able to extrapolate their conclusions, in vitro experiments should mimic the in vivo situation. In vivo, antibacterial capacity depends on multiple steps of bacterial sensing, priming, chemotaxis, phagocytosis and intr...

Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious co...

Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are...

Inflammation in response to infection or trauma can lead to CARS, which is characterized by leukocyte dysfunction. In this study, we used a human model system for CARS to study the effect of GM-CSF and IFN-γ treatment on this immunoparalyzed state. Healthy human volunteers were treated with GM-CSF (4 μg/kg), IFN-γ (100 μg), or placebo in between tw...

Neutrophils are the most abundant white blood cells and are indispensable for host defense. Recently, they have also been implicated in immune regulation and suppression. The latter functions seem hard to reconcile with the widely held view that neutrophils are very short-lived, with a circulatory half-life of <7 h. To reopen the discussion on the...

Background: Severe trauma is characterized by a pronounced immunologic response with both proinflammatory and anti-inflammatory characteristics. The clinical course of trauma patients is often complicated by late-onset (>5 days) sepsis. However, the underlying mechanisms remain poorly defined. Here we studied the kinetics of systemic activation of...

Background Immobilized fibrinogen and fibrin facilitate leukocyte adhesion, as they are potent ligands for leukocyte MAC-1 (CD11b/CD18). However, fibrinogen in its soluble form also binds to MAC-1, albeit with low affinity. The level of soluble fibrinogen is increased during chronic and acute inflammation, but the function of this increase is unkno...

Neutrophils are essential effector cells in the host defense against invading pathogens. Recently, novel neutrophil functions have emerged in addition to their classical anti-microbial role. One of these functions is the suppression of T cell responses. In this respect, neutrophils share similarities with granulocytic myeloid-derived suppressor cel...

Decrease capture under flow and chemotaxis toward fMLF of human CD16bright/CD62Ldim suppressive neutrophils, compared to CD16bright/CD62Lbright and CD16dim/CD62Lbright neutrophils. Neutrophils are essential effector cells in host defense against invading pathogens. Regulation of adhesion, migration, and chemotactic processes is important in the hom...

Polymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to be tightly regulated. Previous studies have invest...

The investigation of the trauma-induced innate immune responses is hampered by the wide variability in patients, type of trauma, and environmental factors. To circumvent this heterogeneity, we examined whether the systemic innate immune response toward human experimental endotoxemia is similar to the response during systemic inflammatory response s...

We have read the comments raised by Tofts and colleagues and Li and colleagues with great interest.We share their surprise about our finding that—under normal homeostatic conditions—peripheral blood neutrophils have an average life span of 5.4 days, and we welcome their constructive replies to this important topic. Taken together, we think the issu...

Apart from their pivotal role in the host defense against pathogens, leukocytes are also essential for bone repair, as fracture healing is initiated and directed by a physiological inflammatory response. Leukocytes infiltrate the fracture hematoma and produce several growth and differentiation factors that regulate essential downstream processes of...

Besides its role in regulation of the complement and contact system, C1-esterase inhibitor has other immunomodulating effects that could prove beneficial in patients with acute inflammation such as during sepsis or after trauma. We examined the immunomodulating properties of C1-esterase inhibitor during human experimental endotoxemia, in which the...

Neutrophils play an important role in host defense. However, deregulation of neutrophils contributes to tissue damage in severe systemic inflammation. In contrast to complications mediated by an overactive neutrophil compartment, severe systemic inflammation is a risk factor for development of immune suppression and as a result, infectious complica...

Multiple organ failure is the main cause of late morbidity and mortality after severe injury. This disease state is driven by a dysfunctional immune system. Prediction of multiple organ failure on the basis of clinical parameters appears to be insufficient. A better understanding of immunological pathogenesis underlying multiple organ failure may l...

Secondary morbidity and mortality after trauma are mainly due to a dysfunctional immune system. Severe injury can trigger a systemic inflammatory response, which is characterised by pre-activation or priming of neutrophils in peripheral blood. Signals initiated as result of local tissue damage can further activate these neutrophils leading to post-...

To evaluate whether patients with hip fracture who undergo surgery within 24 hours--which has been propagated as an indicator of quality care--is associated with a reduced risk of mortality and complications, compared with later surgery. Retrospective status study based on a prospectively designed electronic medical record. Data were collected on p...

A 72-year-old woman had temporary microcalcifications in the nipple area at mammography, possibly caused by skin care products.