Virtual Reality Treatment Displaying the Missing Leg Improves Phantom Limb Pain: A Small Clinical Trial

Background Phantom limb pain (PLP) is a common and in some cases debilitating consequence of upper- or lower-limb amputation for which current treatments are inadequate. Objective This small clinical trial tested whether game-like interactions with immersive VR activities can reduce PLP in subjects with transtibial lower-limb amputation. Methods Seven participants attended 5–7 sessions in which they engaged in a visually immersive virtual reality experience that did not require leg movements (Cool! TM), followed by 10–12 sessions of targeted lower-limb VR treatment consisting of custom games requiring leg movement. In the latter condition, they controlled an avatar with 2 intact legs viewed in a head-mounted display (HTC Vive TM). A motion-tracking system mounted on the intact and residual limbs controlled the movements of both virtual extremities independently. Results All participants except one experienced a reduction of pain immediately after VR sessions, and their pre session pain levels also decreased over the course of the study. At a group level, PLP decreased by 28% after the treatment that did not include leg movements and 39.6% after the games requiring leg motions. Both treatments were successful in reducing PLP. Conclusions This VR intervention appears to be an efficacious treatment for PLP in subjects with lower-limb amputation.

Response to Combination of Pembrolizumab and Axitinib in Hereditary Leyomiomatosis and Renal Cell Cancer (HLRCC)

In current clinical guidelines, such as those provided by the National Comprehensive Cancer Network (NCCN), evidence for treatment is based on a small clinical trial that included patients with HLRCC. They support the use of the combination of erlotinib and bevacizumab as the first therapeutic option in this rare condition. In the present study, we report a rare case of this condition in an 18-year-old male with a family history of kidney cancer whom we successfully treated with surgery and a novel drug treatment modality based on the combination of an immune check-point inhibitor (ICPI) and a tyrosine-kinase inhibitor (TKI) with excellent and promising results.

Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development

Background Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac are effective for colorectal cancer prevention in humans and some animal models, but concerns over gastro-intestinal (GI) ulceration and bleeding limit their potential for chemopreventive use in broader populations. Recently, the combination of aspirin with a phospholipid, packaged as PL-ASA, was shown to reduce GI toxicity in a small clinical trial. However, these studies were done for relatively short periods of time. Since prolonged, regular use is needed for chemopreventive benefit, it is important to know whether GI safety is maintained over longer use periods and whether cancer prevention efficacy is preserved when an NSAID is combined with a phospholipid. Methods As a first step to answering these questions, we treated seven to eight-week-old, male and female C57B/6 Apcmin/+ mice with the NSAID sulindac, with and without phosphatidylcholine (PC) for 3-weeks. At the end of the treatment period, we evaluated polyp burden, gastric toxicity, urinary prostaglandins (as a marker of sulindac target engagement), and blood chemistries. Results Both sulindac and sulindac-PC treatments resulted in significantly reduced polyp burden, and decreased urinary prostaglandins, but sulindac-PC treatment also resulted in the reduction of gastric lesions compared to sulindac alone. Conclusions Together these data provide pre-clinical support for combining NSAIDs with a phospholipid, such as phosphatidylcholine to reduce GI toxicity while maintaining chemopreventive efficacy.

Whole body PD-1 and PD-L1 PET with 89Zr-nivolumab and 18F- BMS-986192 in pts with NSCLC.

e20047 Background: Tumor PD-L1 IHC relates moderately with treatment outcome following anti-PD-(L)1 monotherapy in pts with NSCLC. Aim: 1. To assess safety of the PET procedures. 2. To quantify PD-1 and PD-L1 expression in tumors with 89Zirconium-labeled nivolumab (89Zr-nivo) and 18F-labeled BMS-986192 (18F-PD-L1) PET. 3. To assess intra- and inter-patient tracer uptake differences in tumors. 4. To correlate PET results with IHC and treatment outcome. Methods: NSCLC pts eligible for treatment with nivolumab were included. Pts received a dynamic and static whole body 18F-PD-L1 and a static 89Zr-nivo PET scan. A baseline tumor biopsy was required and up to two additional biopsies were allowed in case PET showed heterogeneous tumor uptake. SUVpeak was calculated for all delineable tumor lesions and related to PD-(L)1 IHC (28.8 assay) and response after 6 wks of nivolumab treatment. Results: 7 pts (5 ≥1%, 2 ≥50% and 2 negative by PD-L1 IHC) were enrolled and 11 lesions analyzed. No toxicity related to radiotracer administration was identified. Tumor uptake of both tracers was visualized in all pts. There was substantial variability among pts for 18F-PD-L1 (mean SUV 5.4, range 2.2 - 14.4) and 89Zr-nivo (mean SUV 5.0, range 1.6 - 9.7). Intra-patient tracer uptake heterogeneity was also seen: mean 2.5-fold (±0.96) and 2.3-fold (±0.86) differences between lesions for 18F-PD-L1 and 89Zr-nivo SUV, respectively. For lesions with < 50% PD-L1 IHC mean 18F-PD-L1 SUV was 3.4 (±2.9) as compared to 7.1 (±6.0) for lesions with ≥50% PD-L1 IHC (p = 0.22). For lesions with low PD-1 expression mean 89Zr-nivo SUV was 6.9 (±2.7) as compared to 8.1 (±2.0) for lesions with high PD-1 expression (p = 0.44). Five pts were evaluable for response evaluation: 1 PR, 2 SD and 2 PD with 18F-PD-L1 SUV values (most PET avid lesion) of 14.4 (PR), 2.0 and 5.4 (SD) and 6.4 and 6.6 (PD). Conclusion: 1.PET-imaging with both tracers is safe and feasible, with good tumor-to-normal tissue contrast. 2. Tumor uptake demonstrated substantial heterogeneity among pts and among tumors within the same pts. 3. Although higher 18F-PD-L1 tumor uptake was seen in pts with ≥50% tumor PD-L1 IHC and the highest 18F-PD-L1 SUV was measured in the responding pt, the dataset is still very small. Clinical trial information: 2015-004760-11.

Pilot Phase IB Clinical Trial of an Alhydrogel-Adsorbed Recombinant Ricin Vaccine

ABSTRACTThere is no FDA-approved vaccine for the potent plant toxin ricin. We have developed a recombinant ricin vaccine, RiVax. Without adjuvant it is safe and immunogenic in mice, rabbits, and humans. Based on our studies in mice, we now report the results of a small clinical trial with Alhydrogel-adsorbed RiVax.

MURMURS AND NOISE CAUSED BY ARTERIAL NARROWING – THEORY AND CLINICAL PRACTICE

Arterial narrowing can cause an audible whirling in the blood flow. We propose diagnosing such narrowing by simply recording that sound and analyzing its spectrum. We show how the Navier-Stokes equation for flow through a narrowing can be turned into a Schrödinger type equation. The complex eigenvalues of the latter equation give the frequencies and decay rates of the vortices present in the whirling pattern. Our diagnosis is based on understanding the relation between features in the sound spectrum and the severity of the narrowing. Today the most commonly used method of diagnosis is duplex ultrasound. In a small clinical trial our method appears to be as good as duplex ultrasound.

Developing alternative devices to the long-term urinary catheter for draining urine from the bladder

The self-retaining urinary catheter is used for long-term drainage of urine from the bladder only as a last resort because of serious associated complications, yet it remains a routine method for managing older and disabled patients with loss of bladder control. Blockage of the catheter from calcified deposits within its lumen is a common occurrence, obstructing the passage of urine and causing an urgent, unpredictable problem for patients, carers and the nursing staff. The need for further research on the subject has been recognized for many years. The SuPort Project aimed to develop an alternative suprapubic urine collection system. This report outlines the approach adopted towards the design and selection of the novel device, the production problems that ensued and the small clinical trial of a modified prototype.