Wilms’ Tumor in a 37-Year-Old

Wilms’ tumor is rare in adults. Though the approach to diagnosis and treatment of adult Wilms’ tumor (AWT) is closely modeled on recommendations for childhood Wilms’ tumor, views differ on how aggressive the treatment should be. We report a case of a 37-year-old with Stage III favorable histology AWT. A radical nephrectomy was performed and the patient was due for chemotherapy. Recent advances, controversies and current recommendations in the treatment of AWT are discussed

Obesity dysregulates the pulmonary antiviral immune response

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals

Obesity dysregulates the pulmonary antiviral immune response

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals

A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications

Obesity dysregulates the pulmonary antiviral immune response

Acknowledgements: M.A. was supported by a Wellcome Trust/Imperial College Clinical Research Training Fellowship. A.J. is supported by an MRC Clinician Scientist Fellowship (MR/Y000935/1). R.J.S. is a Wellcome Trust Senior Research Fellow in Basic Biomedical Sciences (209458/Z/17/Z). S.L.J. is a National Institute for Health Research (NIHR) Emeritus Senior Investigator and received support from the Asthma UK Clinical Chair (Grant CH11SJ), European Research Council Advanced Grants 233015 and 788575, Medical Research Council Centre Grant G1000758 and Asthma UK Centre Grant AUK-BC-2015-01. A.S. is supported by an MRC Clinician Scientist Fellowship (MR/V000098/1). We thank the staff in the Sir Alexander Fleming Building Flow Cytometry Facility for assistance with flow cytometry experiments. This research was supported by the NIHR Imperial Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals

Obesity dysregulates the pulmonary antiviral immune response.

Acknowledgements: M.A. was supported by a Wellcome Trust/Imperial College Clinical Research Training Fellowship. A.J. is supported by an MRC Clinician Scientist Fellowship (MR/Y000935/1). R.J.S. is a Wellcome Trust Senior Research Fellow in Basic Biomedical Sciences (209458/Z/17/Z). S.L.J. is a National Institute for Health Research (NIHR) Emeritus Senior Investigator and received support from the Asthma UK Clinical Chair (Grant CH11SJ), European Research Council Advanced Grants 233015 and 788575, Medical Research Council Centre Grant G1000758 and Asthma UK Centre Grant AUK-BC-2015-01. A.S. is supported by an MRC Clinician Scientist Fellowship (MR/V000098/1). We thank the staff in the Sir Alexander Fleming Building Flow Cytometry Facility for assistance with flow cytometry experiments. This research was supported by the NIHR Imperial Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals