Management of Renal Failure and Ascites in Patients with Cirrhosis

Ascites and renal dysfunction in cirrhosis occur when the liver disease is decompensated and signify the presence of advanced liver failure. However, the precipitating causes should be looked for and treated. Although liver transplantation is the treatment of choice in patients with advanced liver failure, mild to moderate ascites can be treated effectively with medical management. Similarly, renal failure in cirrhotics is reversible if the precipitating causes can be treated effectively and by use of combination of vasoconstrictors and albumin. Transjugular intrahepatic portosystemic shunts also offer an effective therapy for refractory ascites and HRS. Such treatments may offer effective bridge to liver transplantation, by improving short and medium term survivals. Here, we shall discuss all the options available for the management of these complications of cirrhosis

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Autocrine Regulation of Pulmonary Inflammation by Effector T-Cell Derived IL-10 during Infection with Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

In vitro assessment of the effects of valvular stenosis on aorta hemodynamics and left ventricular function

Calcific aortic stenosis (CAS) is the most common valvular heart disease and is associated with aortopathy and ventricular dysfunction. Hemodynamic alterations due CAS could affect the aorta lining (endothelium), that is in direct contact with the blood, triggering adverse biological responses that may possibly cause aortic dilation and dissection. Also, CAS could impose excessive ventricular load leading to ventricular wall thickening, thus putting an individual at a higher risk of heart attack or stroke. These pathophysiological effects of CAS are highly dependent on the degree of calcification. However, the impact of CAS development on aorta flow and left ventricular workload remains largely unknown. Hence the objective of this study is to measure experimentally the effect of CAS on aorta hemodynamics using particle image velocimetry; and left ventricular function in terms of left ventricular work, at different stages of calcification. This study will provide insights on aorta flow abnormalities and left ventricular overload, due CAS, which can be linked to aortopathy and heart failure

Access to

Ascites and renal dysfunction in cirrhosis occur when the liver disease is decompensated and signify the presence of advanced liver failure. However, the precipitating causes should be looked for and treated. Although liver transplantation is the treatment of choice in patients with advanced liver failure, mild to moderate ascites can be treated effectively with medical management. Similarly, renal failure in cirrhotics is reversible if the precipitating causes can be treated effectively and by use of combination of vasoconstrictors and albumin. Transjugular intrahepatic portosystemic shunts also offer an effective therapy for refractory ascites and HRS. Such treatments may offer effective bridge to liver transplantation, by improving short and medium term survivals. Here, we shall discuss all the options available for the management of these complications of cirrhosis