Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml⁻¹, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26–0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.

Lung adenocarcinoma (LUAD)-derived Wnts increase cancer cell proliferative/stemness potential, but whether they impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlates strongly with tolerogenic genes. In another LUAD cohort, Wnt1 inversely associates with T cell abundance. Altering Wnt1 expression profoundly affects growth of murine lung adenocarcinomas and this is dependent on conventional dendritic cells (cDCs) and T cells. Mechanistically, Wnt1 leads to transcriptional silencing of CC/CXC chemokines in cDCs, T cell exclusion and cross-tolerance. Wnt-target genes are up-regulated in human intratumoral cDCs and decrease upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-nanoparticles given as single therapy or part of combinatorial immunotherapies act at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 induces immunologically cold tumors through cDCs and highlight its immunotherapeutic targeting.

Purpose of review This review evaluates recent research findings and proposes an up-to-date diagnostic approach for patients with suspected chylothorax. Recent findings Typically, chylothorax is a milky exudate with high triglyceride content (>110 mg/dl). However, milky appearance is not always the case and triglyceride levels can be less than 110 mg/dl, especially in fasting or malnourished patients. Transudative chylothoraces have been reported when cirrhosis, nephrosis or heart failure co-exist. In addition, although the vast majority of the white blood cells in chyle are lymphocytes, chylothoraces can be neutrophilic, especially the postsurgical ones. Summary Chylothorax is the accumulation of chyle into the pleural cavity usually due to thoracic duct leak and should be suspected not only in patients with milky effusions but also in the presence of certain co-morbidities or history of chest/neck trauma. Fluid triglycerides more than 110 mg/dl or less than 50 mg/dl virtually establish or exclude the diagnosis, respectively; ambiguous cases with values 50–110 mg/dl require lipoprotein analysis for the demonstration of chylomicrons. In fasting or malnourished patients lipoprotein analysis is suggested even with triglycerides less than 50 mg/dl. Typical pleural fluid in chylothorax is a lymphocytic exudate with low lactate dehydrogenase; atypical fluid characteristics (i.e. transudative nature, neutrophil-predominance or high lactate dehydrogenase) may be a sign of additional causes of pleural fluid accumulation.

The term Pulmonary–renal syndrome refers to the combination of diffuse alveolar haemorrhage and rapidly progressive glomerulonephritis. A variety of mechanisms such as those involving antiglomerular basement membrane antibodies, antineutrophil cytoplasm antibodies or immunocomplexes and thrombotic microangiopathy are implicated in the pathogenesis of this syndrome. The underlying pulmonary pathology is small-vessel vasculitis involving arterioles, venules and, frequently, alveolar capillaries. The underlying renal pathology is a form of focal proliferative glomerulonephritis. Immunofluorescence helps to distinguish between antiglomerular basement membrane disease (linear deposition of IgG), lupus and postinfectious glomerulonephritis (granular deposition of immunoglobulin and complement) and necrotizing vasculitis (pauci-immune glomerulonephritis). Patients may present with severe respiratory and/or renal failure and require admission to the intensive care unit. Since the syndrome is characterized by a fulminant course if left untreated, early diagnosis, exclusion of infection, close monitoring of the patient and timely initiation of treatment are crucial for the patient's outcome. Treatment consists of corticosteroids in high doses, and cytotoxic agents coupled with plasma exchange in certain cases. Renal transplantation is the only alternative in end-stage renal disease. Newer immunomodulatory agents such as those causing TNF blockade, B-cell depletion and mycophenolate mofetil could be used in patients with refractory disease.

Colony-Stimulating Factor 1 (CSF1)/Colony-Stimulating Factor Receptor 1 (CSF1R) signaling orchestrates tumor-associated macrophage (TAM) recruitment and polarization towards a pro-tumor M2 phenotype, the dominant phenotype of TAMs infiltrating mesothelioma tumors. We hypothesized that CSF1/CSF1R inhibition would halt mesothelioma growth by targeting immunosuppressive M2 macrophages and unleashing efficient T cell responses. We also hypothesized that CSF1/CSF1R blockade would enhance the efficacy of a PDL1 inhibitor which directly activates CD8+ cells. We tested a clinically relevant CSF1R inhibitor (BLZ945) in mesothelioma treatment using syngeneic murine models. We evaluated the role of CSF1/CSF1R axis blockade in tumor-infiltrating immune subsets. We examined the effect of combined anti-CSF1R and anti-PDL1 treatment in mesothelioma progression. CSF1R inhibition impedes mesothelioma progression, abrogates infiltration of TAMs, facilitates an M1 anti-tumor phenotype and activates tumor dendritic and CD8+ T cells. CSF1R inhibition triggers a compensatory PD-1/PDL1 upregulation in tumor and immune cells. Combined CSF1R inhibitor with an anti-PDL1 agent was more effective in retarding mesothelioma growth compared to each monotherapy. In experimental mesotheliomas, CSF1R inhibition abrogates tumor progression by limiting suppressive myeloid populations and enhancing CD8+ cell activation and acts synergistically with anti-PDL1.

Evidence to date suggests that a significant proportion of COVID-19 patients experience adverse psychological outcomes and neuropsychiatric complications. The aim of this study was to evaluate the effect of SARS-CoV-2 infection and subsequent hospitalization on the mental health, sleep, and quality of life of COVID-19 survivors. Patients were assessed 1–2 months after hospital discharge using standardized screening tools for depression and anxiety (HADS), post-traumatic stress disorder (IES-R), insomnia (AIS), and quality of life (EQ-5D-5L). Sociodemographic factors, comorbidities, disease severity and type of hospitalization were also collected. Amongst the 143 patients included, mental health symptoms were common (depression—19%; anxiety—27%; traumatic stress—39%; insomnia—33%) and more frequently reported in female than in male patients. Age, smoking status, comorbidities and illness severity were not found to significantly correlate with the presence of mood, sleep, or stress disorders. Finally, quality of life was worse for patients requiring ICU (p = 0.0057) or a longer hospital stay (p < 0.001) but was unaffected by factors such as sex and other measured outcomes. These findings highlight the need for appropriate intervention to properly manage the immediate and enduring mental health complications of COVID-19.