The hypoxia-age-shock index at triage to predict the outcomes of Covid-19 patients.

STUDY OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has caused a severe burden on medical professionals, as the rapid disposition of patients is important. Therefore, we aimed to develop a new clinical assessment tool based on the shock index (SI) and age-shock index (ASI). We proposed the hypoxia-age-shock index (HASI) and determined the usability of triage for COVID-19 infected patients in the first scene. METHODS: The predictive power for three indexes on mortality, intensive care unit (ICU) admission, and endotracheal intubation rate was evaluated using the receiver operating curve (ROC). We used DeLong's method for comparing the ROCs. RESULTS: The area under the curve (AUC) for ROC on mortality for SI, ASI, and HASI were 0.546, 0.771, and 0.773, respectively. The AUC on ICU admission mortality for SI, ASI, and HASI were 0.581, 0.700, and 0.743, respectively. The AUC for intubation for SI, ASI, and HASI were 0.592, 0.708, and 0.757, respectively. The AUC differences between HASI and SI showed statistically significant (P = 0.001) results on mortality, ICU admission, and intubation. Additionally, statistically significant results were found for the AUC difference between the HASI and ASI on ICU admission and intubation (P = 0.001 and P = 0.004, respectively). CONCLUSION: HASI can provide a better prediction compared to ASI on ICU admission and endotracheal intubation. HASI was more sensitive in mortality, ICU admission, and intubation prediction than the ASI.

GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) has shown activity in treating relapsed or refractory multiple myeloma; however, relapse is still common, and new targets are needed. We aimed to assess the activity and safety profile of G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma. METHODS: POLARIS was a first-in-human, single-centre, single-arm, phase 1 trial of GPRC5D-targeted CAR T cells (OriCAR-017) done at the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. Eligible patients were adults aged 18-75 years with a diagnosis of relapsed or refractory multiple myeloma and an ECOG performance status of 0-2, had GPRC5D expression in bone marrow plasma cells greater than 20% or were positive for GPRC5D by immunohistochemistry, and had received at least three previous lines of treatment including proteasome inhibitors, immunomodulatory drugs, and chemotherapy. Patients were consecutively assigned to receive a single dose of intravenous OriCAR-017 at 1 × 106 CAR T cells per kg, 3 × 106 CAR T cells per kg, or 6 × 106 CAR T cells per kg in the dose-escalation phase. In the expansion phase, patients received the recommended phase 2 dose. Recruitment to the expansion phase terminated early due to the COVID-19 pandemic on May 1, 2022. The primary endpoints were safety, the maximum tolerated dose and the recommended phase 2 dose. Safety and activity analyses included all patients who received OriCAR-017. This trial is registered with ClinicalTrials.gov, NCT05016778. This trial has been completed and is entering long-term follow-up. FINDINGS: Between June 9, 2021, and Feb 28, 2022, we recruited 13 patients for inclusion into the study. One patient was excluded because of GPRC5D negativity and two patients discontinued after apheresis because of rapid progression. Nine patients were assigned to the dose escalation phase (three received 1 × 106 CAR T cells per kg, three received 3 × 106 CAR T cells per kg, and three received 6 × 106 CAR T cells per kg). The maximum tolerated dose was not identified, because no dose-limiting toxic effects were observed. On the basis of safety and preliminary activity, the recommended phase 2 dose was set at 3 × 106 CAR T cells per kg, which was received by one additional patient in the dose expansion phase. Five patients (50%) were female, five (50%) were male, and all were Chinese. Five patients (50%) were previously treated with BCMA-targeted CAR T-cell therapy. Median follow-up was 238 days (IQR 182-307). There were no serious adverse events and no treatment-related deaths. The most common grade 3 or worse adverse events were haematological, including neutropenia (ten [100%] of ten patients), thrombocytopenia (nine [90%]), leukopenia (nine [90%]), and anaemia (seven [70%]). All patients had cytokine release syndrome (nine [90%] grade 1 and one [10%] grade 2). No neurological toxic effects were reported. Ten (100%) of ten patients had an overall response, of whom six (60%) had a stringent complete response and four (40%) had very good partial response. Two patients discontinued due to disease progression (one GPRC5D-positive patient in the middle-dose group and one GPRC5D-negative patient in the low-dose group). INTERPRETATION: The results of this study suggest that GPRC5D is an active target for immunotherapy in multiple myeloma. GPRC5D-targeted CAR T-cell therapy is a promising treatment modality for patients with relapsed or refractory multiple myeloma and deserves further testing. FUNDING: OriCell Therapeutics.

Diffused bladder wall calcification in a survivor with severe coronavirus disease 2019: A case report.

RATIONALE: Bladder calcification is a rare presentation that was first interpreted to be related to a urea-splitting bacterial infection. Aside from infection, other hypotheses such as schistosomiasis, tuberculosis, cancer, and cytokine-induced inflammatory processes have also been reported. Severe coronavirus disease 2019 (COVID-19) is known for its provoking cytokine storm and uninhibited systematic inflammation, and calcification over the coronary artery or lung has been reported as a long-term complication. PATIENT CONCERNS: We presented a 68 years old man who had persistent lower urinary tract symptoms after recovery from severe COVID-19. No urea-splitting bacteria were identified from urine culture. DIAGNOSIS: Cystoscopy examination revealed diffuse bladder mucosal and submucosa calcification. INTERVENTIONS: Transurethral removal of the mucosal calcification with lithotripsy. OUTCOMES: The patient's lower urinary tract symptoms improved, and stone analysis showed 98% calcium phosphate and 2% calcium oxalate. No newly formed calcifications were found at serial follow-up. CONCLUSION: Diffuse bladder calcification may be a urinary tract sequela of COVID-19 infection. Patients with de novo lower urinary tract symptoms after severe COVID-19 should be further investigated.

CONFIDENCE LEVEL OF A MOTION FEEDBACK SYSTEM FOR ANALYZING EXERCISE TRAINING EFFICACY: APPLICATIONS, BASIS, AND COMMUNICATIONS

The increase in aged population is a global trend. Inculcating healthy behaviors such as regular exercises in the elderly has a significant impact on the financial and medical burden globally. Moreover, air pollution and the outbreak of the coronavirus disease 19 (COVID-19) pose a serious threat to public health. In order to improve the health conditions of the population, this study developed a motion feedback system named MoveV that can be used for several indoor training exercises. This system provides instant motion feedback by synchronizing exercise training videos on the website using a motion analysis algorithm that is applicable on smartphones, and a cloud database platform is used to record health behaviors. Feature extraction is performed based on force intensity, motion velocity, and exercise direction. The resultant accuracy of the motion feedback system was tested by a motion science expert and presented as the confidence level. For perfect movement, a confidence level of up to 90.5% was achieved, indicating that the MoveV system was able to record users’ exercise frequency and distinguish whether the user was performing well in the exercise movements. The proposed system is convenient and does not incur additional expenditure by purchasing any new device. Furthermore, it provides visual and voice feedback, companionship, and exercise motivation to the users, all of which are important factors when using online exercise platforms.

CAR T-cell treatment during the COVID-19 pandemic: Management strategies and challenges.

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly across the world. Currently, the COVID-19 pandemic is affecting the continuity of essential routine healthcare services and procedures, including chimeric antigen receptor T-cell (CAR-T) therapy, a life-saving option for patients with relapsed/refractory (R/R) hematologic malignancies. Due to the rapid disease progression of hematological malignancies, there is an urgent need to manufacture and utilize CAR T-cells. However, CAR-T treatment has become extraordinarily challenging during this COVID-19 pandemic. Thus, many medical and technical factors must now be taken into consideration before, during, and after CAR-T therapy. The purpose of this review is to provide brief suggestions for rational decision-making strategies in evaluating and selecting CAR T-cell treatment and appropriate CAR T-cell products, and protective strategies for medical staff and patients to prevent infection in the midst of the current COVID-19 pandemic.