SEAttle-based Research of Chinese Herbs for COVID-19 Study: A Whole Health Perspective on Chinese Herbal Medicine for Symptoms that may be Related to COVID-19.

INTRODUCTION: East Asian Medicine (EAM) is a Whole System medicine that includes Chinese herbal medicine (CHM). Chinese herbal medicine has been utilized to reduce symptom burden in infectious disease, with notable theoretical reformulations during pandemics of the 3rd, 13th, and 17th centuries. Today, Licensed Acupuncturists trained in CHM have utilized it to treat symptoms and sequelae of COVID-19. However, little is known about its use or efficacy by the public and health practitioners. Understanding and evaluating whole medicine systems of healthcare is inherently complex; there is international consensus for a descriptive, pragmatic approach. We are conducting a feasibility pilot study using a prospective, pragmatic, observational design using Whole Health and Whole Person perspectives. The complexity of COVID-19 reflects the impact on multiple homeoregulatory systems and provides a unique opportunity to assess the impact of interventions such as EAM on whole health. Observation of these EAM encounters will provide valuable qualitative and quantitative data on the interface of an extant Whole System medicine with a novel complex illness as a precursor to a randomized clinical trial. METHODS: This ongoing study observes a CHM clinic offering telehealth consultations to a diverse patient population since April, 2020. Patients who report symptoms potentially related to COVID-19 disease are consented for standardized collection and analysis of demographic and clinical data from each clinical encounter. RESULTS: To date, 61 patients engaged in 195 consultations (mean 3.3) with 49 reporting symptom resolution sufficient to complete treatment, and 4 withdrawals. Just over half (62%) were female, with an average age of 45.7 years. A wide variety of CHM formulas and EAM dietary and lifestyle modifications were provided. DISCUSSION: Adequate recruitment and retention suggest feasibility of the intervention and data collection. The rich dataset may facilitate the construction of Whole Health models of CHM's clinical impact, as well as integrative inquiry into CHM's effects on symptoms.

Dose-escalation study of vemurafenib with sorafenib or crizotinib in patients with BRAF-mutated advanced cancers.

BACKGROUND: BRAF inhibitors are effective in melanoma and other cancers with BRAF mutations; however, patients ultimately develop therapeutic resistance through the activation of alternative signaling pathways such as RAF/RAS or MET. The authors hypothesized that combining the BRAF inhibitor vemurafenib with either the multikinase inhibitor sorafenib or the MET inhibitor crizotinib could overcome therapeutic resistance. METHODS: Patients with advanced cancers and BRAF mutations were enrolled in a dose-escalation study (3 + 3 design) to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of vemurafenib with sorafenib (VS) or vemurafenib with crizotinib (VC). RESULTS: In total, 38 patients (VS, n = 24; VC, n = 14) were enrolled, and melanoma was the most represented tumor type (VS, 38%; VC, 64%). In the VS arm, vemurafenib 720 mg twice daily and sorafenib 400 mg am/200 mg pm were identified as the MTDs, DLTs included grade 3 rash (n = 2) and grade 3 hypertension, and partial responses were reported in 5 patients (21%), including 2 with ovarian cancer who had received previous treatment with BRAF, MEK, or ERK inhibitors. In the VC arm, vemurafenib 720 mg twice daily and crizotinib 250 mg daily were identified as the MTDs, DLTs included grade 3 rash (n = 2), and partial responses were reported in 4 patients (29%; melanoma, n = 3; lung adenocarcinoma, n = 1) who had received previous treatment with BRAF, MEK, and/or ERK inhibitors. Optional longitudinal collection of plasma to assess dynamic changes in circulating tumor DNA demonstrated the elimination of BRAF-mutant DNA from plasma during therapy (P = .005). CONCLUSIONS: Vemurafenib combined with sorafenib or crizotinib was well tolerated with encouraging activity, including among patients who previously received treatment with BRAF, MEK, or ERK inhibitors.

Stiffness Perception using Transcutaneous Electrical Stimulation during Active and Passive Prosthetic Control.

Haptic feedback allows an individual to identify various object properties. In this preliminary study, we determined the performance of stiffness recognition using transcutaneous nerve stimulation when a prosthetic hand was moved passively or was controlled actively by the subjects. Using a 2x8 electrode grid placed along the subject's upper arm, electrical stimulation was delivered to evoke somatotopic sensation along their index finger. Stimulation intensity, i.e. sensation strength, was modulated using the fingertip forces from a sensorized prosthetic hand. Object stiffness was encoded based on the rate of change of the evoked sensation as the prosthesis grasped one of three objects of different stiffness levels. During active control, sensation was modulated in real time as recorded forces were converted to stimulation amplitudes. During passive control, prerecorded force traces were randomly selected from a pool. Our results showed that the accuracy of object stiffness recognition was similar in both active and passive conditions. A slightly lower accuracy was observed during active control in one subject, which indicated that the sensorimotor integration processes could affect haptic perception for some users.

Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209).

PURPOSE: Limitations of the paclitaxel-doxorubicin-cisplatin (TAP) regimen in the treatment of endometrial cancer include tolerability and cumbersome scheduling. The Gynecologic Oncology Group studied carboplatin plus paclitaxel (TC) as a noninferior alternative to TAP. METHODS: GOG0209 was a phase III, randomized, noninferiority, open-label trial. Inclusion criteria were stage III, stage IV, and recurrent endometrial cancers; performance status 0-2; and adequate renal, hepatic, and marrow function. Prior radiotherapy and/or hormonal therapy were permitted, but chemotherapy, including radiosensitization, was not. Patients were treated with doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 (day 1), followed by paclitaxel 160 mg/m2 (day 2) with granulocyte colony-stimulating factor or paclitaxel 175 mg/m2 and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles. The primary endpoint was overall survival (OS; modified intention to treat). Progression-free survival (PFS), health-related quality of life (HRQoL), and toxicity were secondary endpoints. RESULTS: From 2003 to 2009, 1,381 women were enrolled. Noninferiority of TC to TAP was concluded for OS (median, 37 v 41 months, respectively; hazard ratio [HR], 1.002; 90% CI, 0.9 to 1.12), and PFS (median, 13 v 14 months; HR, 1.032; 90% CI, 0.93 to 1.15). Neutropenic fever was reported in 7% of patients receiving TAP and 6% of those receiving TC. Grade > 2 sensory neuropathy was recorded in 26% of patients receiving TAP and 20% receiving TC (P = .40). More grade ≥ 3 thrombocytopenia (23% v 12%), vomiting (7% v 4%), diarrhea (6% v 2%), and metabolic (14% v 8%) toxicities were reported with TAP. Neutropenia (52% v 80%) was more common with TC. Small HRQoL differences favored TC. CONCLUSION: With demonstrated noninferiority to TAP, TC is the global first-line standard for advanced endometrial cancer.

Reduction of metabolic cost during motor learning of arm reaching dynamics.

It is often assumed that the CNS controls movements in a manner that minimizes energetic cost. While empirical evidence for actual metabolic minimization exists in locomotion, actual metabolic cost has yet to be measured during motor learning and/or arm reaching. Here, we measured metabolic power consumption using expired gas analysis, as humans learned novel arm reaching dynamics. We hypothesized that (1) metabolic power would decrease with motor learning and (2) muscle activity and coactivation would parallel changes in metabolic power. Seated subjects made horizontal planar reaching movements toward a target using a robotic arm. The novel dynamics involved compensating for a viscous curl force field that perturbed reaching movements. Metabolic power was measured continuously throughout the protocol. Subjects decreased movement error and learned the novel dynamics. By the end of learning, net metabolic power decreased by ~20% (~0.1 W/kg) from initial learning. Muscle activity and coactivation also decreased with motor learning. Interestingly, distinct and significant reductions in metabolic power occurred even after muscle activity and coactivation had stabilized and movement changes were small. These results provide the first evidence of actual metabolic reduction during motor learning and for a reaching task. Further, they suggest that muscle activity may not explain changes in metabolic cost as completely as previously thought. Additional mechanisms such as more subtle features of arm muscle activity, changes in activity of other muscles, and/or more efficient neural processes may also underlie the reduction in metabolic cost during motor learning.