Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.

Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

The use of multi-site photoplethysmography (PPG) as a screening tool for coronary arterial disease and atherosclerosis.

Objective. We present the design and validation of a non-invasive smart-phone based screening tool for atherosclerosis and coronary arterial disease (CAD), which is the leading cause of mortality worldwide.Approach. We designed a three-channel photoplethysmography (PPG) device that connects to a smart phone application for measuring pulse transit time (PTT) and pulse wave velocity (PWV) using PPG probes that are simultaneously clipped onto to the ear, index finger, and big toe, respectively. Validation was performed through a clinical study with 100 participants (age 20 to 77) at a research hospital in Nagpur, India. Study subjects were stratified by age and divided into three groups corresponding to the disease severity: CAD, hypertensive ('Pre-CAD'), and Healthy.Main results. PWV measurements derived from the Ear-Toe probe measurements yielded the best performance, with median PWV values increasing monotonically as a function of disease severity and age, as follows: 14.2 m s-1for the older-patient CAD group, 12.2 m s-1for the younger-patient CAD group, 11.6 m s-1for the older-patient Pre-CAD group, 10.2 m s-1for the younger-patient Pre-CAD group, 9.7 m s-1for the older healthy controls, and 8.4 m s-1for the younger healthy controls. Using just two simple features, the PTT and patient height, we demonstrate a machine learning prediction model for CAD with a median accuracy of 0.83 (AUC).Significance. This work demonstrates the ability to predict atherosclerosis and CAD using a single simple physiological measurement with a multi-site PPG tool that is electrically powered by a mobile phone and does not require any electrocardiogram reference. Furthermore, this method only requires a single anthropometric measurement, which is the patient's height.

Low-Cost Mobile Device for Screening of Atherosclerosis and Coronary Arterial Disease.

In the context of global health, telemedicine, and low-resource settings, we present a non-invasive smart-phone based device that can be used to screen for atherosclerosis,which is the leading factor for ischemic heart attacks and strokes. Using acustom Android mobile application, our device computes Pulse Wave Velocity(PWV) using the pulse signals from photo-plethysmographic (PPG) probes, which are simultaneously clipped onto the ear, index finger, and big toe of a human subject. Unlike other designs which require the use of an ECG reference, our mobile device uses only PPG signals and is entirely powered by the mobile phone via the USB port. Using the ear signal as a reference, we derived PWV values from two locations: the right index finger, and the right big toe.We present data from a recent clinical study with 78 participants (age 26 to 74) who were divided into three groups: Coronary Arterial Disease ("CAD"), hypertensive group ("PreCAD"), and Healthy controls. The CAD group was clinically diagnosed and confirmed with a CT-scan and calcium scoring. PWV values derived from the finger was found to have too much variance to be clinically useful. However, PWV values derived from the toe location showed significant differences between the groups, even after accounting for age. Measured PWV values were: 10.07 (8.51-12.01) for the older CAD group, 9.39 (7.44-9.75) for the younger CAD group, 8.26 (7.26-9.22) for the older Pre-CAD group, 10.57 m/s (8.5-11.2) for the younger Pre-CAD group, 7.13 m/s (5.97-7.69) for older healthy controls, and 6.71 m/s (4.86-7.26) for the younger healthy control subjects. These results demonstrate good potential value of this mobile PWV device as a simple low-cost screening tool for atherosclerosis and coronary arterial disease.

Integrin-targeted cancer immunotherapy elicits protective adaptive immune responses.

Certain RGD-binding integrins are required for cell adhesion, migration, and proliferation and are overexpressed in most tumors, making them attractive therapeutic targets. However, multiple integrin antagonist drug candidates have failed to show efficacy in cancer clinical trials. In this work, we instead exploit these integrins as a target for antibody Fc effector functions in the context of cancer immunotherapy. By combining administration of an engineered mouse serum albumin/IL-2 fusion with an Fc fusion to an integrin-binding peptide (2.5F-Fc), significant survival improvements are achieved in three syngeneic mouse tumor models, including complete responses with protective immunity. Functional integrin antagonism does not contribute significantly to efficacy; rather, this therapy recruits both an innate and adaptive immune response, as deficiencies in either arm result in reduced tumor control. Administration of this integrin-targeted immunotherapy together with an anti-PD-1 antibody further improves responses and predominantly results in cures. Overall, this well-tolerated therapy achieves tumor specificity by redirecting inflammation to a functional target fundamental to tumorigenic processes but expressed at significantly lower levels in healthy tissues, and it shows promise for translation.