Characteristics of Traditional Chinese Medicine Syndromes and Treatments of COVID-19 Patients from Two Hospitals Based on "Treatment of Disease in Accordance with Three Conditions".

Objective: To explore the guidance value of "treatment of disease in accordance with three conditions" theory in the prevention and treatment of corona virus disease 2019 (COVID-19) based on the differences of syndromes and traditional Chinese medicine (TCM) treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. Method(s): Demographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system (HIS) of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. Result(s): A total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai, dominated by young and middle-aged males, had clinical symptoms of fever, abnormal sweating, and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat, with manifest cold, dampness, and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness, accompanied by draining depressed heat. The core Chinese medicines used are Poria, Armeniacae Semen Amarum, Gypsum Fibrosum, Citri Reticulatae Pericarpium, and Pogostemonis Herba. By contrast, the 105 patients in Ruili, dominated by young females, had atypical clinical symptoms, and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach, with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen, resolving dampness, and dispersing Qi with light drugs. The core Chinese medicines used are Poria, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Coicis Semen, Platycodonis Radix, Lonicerae Japonicae Flos, and Pogostemonis Herba. Conclusion(s): The differences in clinical characteristics, TCM syndromes, and medication of COVID-19 patients from the two places may result from different regions, population characteristics, and the time point of the COVID-19 outbreak. The "treatment of disease in accordance with three conditions" theory can help to understand the internal correlation and guide the treatments.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Preparation of green-solvent-based polyamide nanofiber membrane and its air filtration performance

Objective The epidemic of COVID-19 and its variants is endangering human health. Wearing protective masks can effectively reduce the infection risk by resisting the inhalation of the polluted air containing the coronavirus. Electrospun polyamide nanofibers can be used as the core layer of protective masks and have lately received growing attention because of their high filtration performance and robust mechanical properties. However, existing electrospun polyamide nanofiber filters are usually prepared from toxic solvents which could cause severe environmental pollution and endanger workers' health, hence, their practical application should be restricted. Therefore, it is imperative to seek and develop green-solvent-based polyamide nanofiber filters. Method Innovative polyamide nanofiber filters were developed by direct electrospinning technique based on green solvents (Fig. 1). Ethanol as the solvent and water as the nonsolvent were adopted to prepare the green-solvent-based polyamide (GSPA) nanofibers by designing spinning solutions with different ethanol/water mass ratios (i.e., 10: 0, 9: 1, 8: 2, 7: 3, and 6: 4) . During electrospinning process, the working voltage, tip-to-collector distance, and solution extrusion speed were set as 30 kV, 15 cm and 1 mL/h, respectively. The nanofibers prepared with the different ethanol/water ratios were denoted as GSPA - 0, GSPA - 1, GSPA - 2, GSPA-3, and GSPA-4, respectively. Results It was found that water content had a great influence on the morphological structures of polyamide nanofibers (Fig. 2) - After introducing a small amount of water, the obtained GSPA - 1 nanofibers featuring thinner diameter of 332 nm were compared to the GSPA-0 nanofibers (499 nm). The enhanced conductivity (10. 5 μS/cm) of waterborne spinning solutions (Fig. 3) stimulated more charges on spinning jets and led to larger electrostatic force, thus greatly elongating the jets and thinning the fiber diameter. However, with the further increment of water concentrations from 20% to 40%, the obtained fibers exhibited an increased average diameter ranging from 443 to 1 553 nm, which was mainly attributed to the larger viscosity of spinning solutions. Although water cannot dissolve polyamide, homogenous waterborne polyamide/ethanol solutions can still be obtained with different ethanol/water mass ratios within a broad area in the stable region (Fig. 3) - The average pore size of GSPA -1 membranes decreased by 55% compared with that of GSPA-0 membranes, contributing to high filtration efficiency. Moreover, with different concentrations (10%, 20%, 30%) of water, the fluffy structure of GSPA nanofibers were achieved with a high porosity (> 80%), which would offer more passageways to transmit air rapidly. As the water concentration increased, the breaking strength of membranes increased at first and then decreased (Fig. 5), and the GSPA- 1 membranes exhibited the highest breaking strength of 5. 6 MPa, which was believed to be related to the enhanced entanglements and contacts among the adjacent fibers because of the small fiber diameter. The GSPA -1 membranes displayed the highest filtration efficiency (99. 02%) for the most penetration particles (PM0.3) by virtue of the small fiber diameter but suffered from poor permeability with a pressure drop of 158 Pa. Moreover, the GSPA- 1 membranes possessed the highest quality factor of 0. 029 3 Pa, suggesting the optimal filtration performance among different GSPA membranes. A high PM0.3 removal efficiency (>95%) was achieved for GSPA-1 filters under various airflow velocities ranging from 10 to 90 L/min (Fig. 7). Compared with conventional melt-blown fibers, the GSPA nanofibers featured a smaller diameter and higher Knudsen number (Fig. 8), and PM0.3 were captured mainly on the surfaces of green polyamide nanofibers (Fig. 9), demonstrating the higher adsorption ability benefiting from the larger specific surface area. Conclusion A cleaner production of polyamide nanofibers for air filtration was proposed by direct electrospinning based on green and sustaina le binary solvents of water and ethanol. For the first time, the structure including fiber diameter, porosity, and pore size of electrospun polyamide nanofibers were precisely tailored by manipulating water concentration in spinning solutions. The prepared environmentally friendly polyamide nanofiber filters feature the interconnected porous structure with the nanoscale ID building blocks (332 nm), mean pore size (0.7 μm), and porosity (84%), thus achieving efficient PM0.3 capture performance with the filtration efficiency of 99. 02% and pressure drop of 158 Pa, which could be comparable to previous toxic-solvent-processed nanofibers. Moreover, the GSPA nanofibers exhibit robust mechanical properties with an impressive breaking strength (5 . 6 MPa) and elongation (163. 9%), contributing to withstanding the external forces and deformation in the practical assembly and usage of resultant filters. It is envisaged that the green-solvent-based polyamide nanofibers could be used as promising candidates for next-generation air filters, and the proposed waterborne spinning strategy can provide valuable insights for cleaner production of advanced polyamide textiles. © 2023 China Textile Engineering Society. All rights reserved.

V-tube: The first prototype of pneumatic actuated soft nasal swab for COVID-19 screening

Swab and tube are widely used in respiratory specimen collections for current COVID-19 screening. This paper proposes the design of a novel pneumatic actuated soft nasal swab, named V-tube. The V-tube consists of three main parts: an outer tube, a cap integrated with broth container and an active film (AF) that can be squeezed out of the tube under positive air pressure to collect nasal mucus cells. The working process and material selection of this swab is studied via Finite Element Analysis (FEA). It is expected to integrate the V-tube with a dual arm mobile collaborative robot (MCR) to accomplish nucleic acid sampling instead of medical staff. Therefore, a robot-applicable pneumatic system is designed to supply appropriate force to drive the V-tube. The potential manufacturing and control issues of the V-tube are discussed for further studies. © 2022 IEEE.

Prevalence and Associated Factors of Very Early Cognitive Impairment in COVID-19 Convalescents：a Study Using Data from a Questionnaire Survey

【】 Background COVID-19 may impair the central nervous system，but the prevalence and related factors of very early cognitive impairment in discharged COVID-19 convalescents are still unclear. Objective To assess the prevalence of very early cognitive impairment in discharged COVID-19 convalescents，and to identify its influencing factors. Methods This study included 574 COVID-19 convalescents from August 28 to September 30，2020，including individuals who were discharged from designated hospitals for treating COVID-19 in Wuhan from December 2019 to April 2020 randomly selected from the hospital information system，and those with informed consent recruited through news media. According to the Eight-item Informant Interview to Differentiate Aging and Dementia（AD8）score，the subjects were divided into a very early cognitive impairment group（AD8 ≥ 2）and a non-very early cognitive impairment group（AD8<2）. A questionnaire survey was conducted with the subjects by four investigators at Hubei Provincial Hospital of Traditional Chinese ＆amp;Western Medicine，using the General Information Questionnaire to collect demographic information and past disease history of the patients（including gender，age，underlying disease，classification of COVID-19 on admission，interval between discharge and the current survey，and various symptoms present at the time of follow-up），using the Generalized Anxiety Disorder-7（GAD-7），the PTSD Check List–Civilian Version（PCL-C），and the Short Form 36 Health Survey Questionnaire（SF-36）to assess patients' anxiety，post-traumatic stress disorder，and quality of life，respectively. Three hundred and eleven cases finally completed the cognitive function screening. Multiple Logistic regression was used to evaluate the effects of gender，age，underlying disease and admission classification of COVID-19 on very early cognitive impairment. A restricted cubic spline model was used to assess the quantitative relationship between anxiety level and very early cognitive impairment. Results 311（54.18%）who effectively responded to the survey was finally enrolled，including 170（54.7%）with very early cognitive impairment and 141（45.3%）without. 230 （23.9%）had residual symptoms after discharge. Comparisons of gender，age，insomnia，fatigue，chest tightness，shortness of breath，loss of appetite，generalized anxiety disorder，PTSD positive，and the score of each SF-36 entry among COVID-19 convalescents with and without very early cognitive impairment were statistically significant（P<0.05）. Multivariate Logistic regression analysis suggested that females〔OR（95%CI）=2.658（1.528，4.625）〕，advanced age〔OR（95%CI）=3.736（1.083，12.890）〕，and having generalised anxiety disorder〔OR（95%CI）=5.081（1.229，21.008）〕were influential factors in increasing very early cognitive impairment（P<0.05）. Restricted cubic spline models indicated a linear quantitative relationship between anxiety level and very early cognitive impairment，with higher levels of anxiety associated with a greater likelihood of very early cognitive impairment（P for non-linear test =0.132）. Conclusion The incidence of very early cognitive impairment is high in COVID-19 convalescents，and it may be higher in those who are older，female，or have generalized anxiety symptoms. Timely interventions for psychiatric problems and alleviation of anxiety symptoms in COVID-19 convalescents，especially in older women，may help to improve their cognitive function and Alzheimer's disease. © 2023 Chinese General Practice. All rights reserved.

Application of XOLAIR® (Omalizumab) in adolescent refractory chest tightness variant asthma.

BACKGROUND: Asthma can manifest in a variety of clinical phenotypes like cough variant asthma, chest tightness variant asthma (CTVA), and masked asthma. Patients with CTVA usually have a singular or primary complaint of chest tightness, which is often overlooked or misdiagnosed due to the lack of characteristic asthma symptoms. We hereby report a case of CTVA managed by omalizumab. CASE REPORT: A 15-year-old female patient reported to us with repeated coughing persisting for 3 weeks. Initial treatment with standard asthma drugs had minimal effect. Later during the disease, chest tightness became the primary symptom, and she was managed with steroids, ß2 receptor agonists, and leukotriene receptor agonists but without complete relief. Based on clinical signs and symptoms, the response to baseline drugs, and results of bronchial provocation test, the diagnosis was revised to CTVA, and the patient was started on Omalizumab in addition to baseline drugs, which significantly improved her condition. CONCLUSIONS: CTVA is difficult to diagnose due to its insidious symptoms and poor characteristics. Improper treatment can lead to uncontrolled disease, negative psychological issues, and reduced quality of life. Comprehensive assessment of children's airway inflammation level, lung function, bronchial provocation test, and responsiveness to drug therapy should be performed for accurate diagnosis. Omalizumab in combination with standard drugs can significantly improve the outcomes of CTVA.

Characteristics of Traditional Chinese Medicine Syndromes and Treatments of COVID-19 Patients from Two Hospitals Based on “Treatment of Disease in Accordance with Three Conditions”

Objective: To explore the guidance value of “treatment of disease in accordance with three conditions” theory in the prevention and treatment of corona virus disease 2019 (COVID-19) based on the differences of syndromes and traditional Chinese medicine (TCM) treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. Method: Demographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system (HIS) of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. Result: A total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai, dominated by young and middle-aged males, had clinical symptoms of fever, abnormal sweating, and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat, with manifest cold, dampness, and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness, accompanied by draining depressed heat. The core Chinese medicines used are Poria, Armeniacae Semen Amarum, Gypsum Fibrosum, Citri Reticulatae Pericarpium, and Pogostemonis Herba. By contrast, the 105 patients in Ruili, dominated by young females, had atypical clinical symptoms, and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach, with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen, resolving dampness, and dispersing Qi with light drugs. The core Chinese medicines used are Poria, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Coicis Semen, Platycodonis Radix, Lonicerae Japonicae Flos, and Pogostemonis Herba. Conclusion: The differences in clinical characteristics, TCM syndromes, and medication of COVID-19 patients from the two places may result from different regions, population characteristics, and the time point of the COVID-19 outbreak. The “treatment of disease in accordance with three conditions” theory can help to understand the internal correlation and guide the treatments. © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Autoclavable, Breathable, and Waterproof Membranes Tailored by Ternary Nanofibers for Reusable Medical Protective Applications

The COVID-19 created severe shortages of prevention materials and supplies, and the reuse of medical protective clothing is ongoing worldwide. However, it has remained a significant challenge to realize the reusability of the current medical protective clothing. We reported a scalable strategy to create autoclavable ternary electrospun nanofibrous membranes (TENMs) by introducing the elastomer polyurethane (PU) and low-surface-energy fluorinated polyurethane (FPU) into poly(ether sulfone) (PES) fibers via electrospinning. The advantage of this design was that we could balance the waterproof-breathable function and the thermostable performance of the membrane by controlling the PES/PU/FPU mass ratio. The resulting TENMs showed excellent performances of a high moisture transmission rate of 8.3 kg m-2 day-1, a high hydrostatic pressure of 82.56 kPa, a high bacteria retention rate of 99.99%, a high aerosol retention rate of 99.99%, and autoclave sterilization-invariant to 10 cycles. The successful preparation of the material can lead to the reuse of medical protective clothing in the foreseeable future. © 2021 American Chemical Society.

Clinical characteristics of coronavirus disease 2019 infected with Delta variant in Guangzhou:A real-world study

Objective To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment. Methods A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University. Results The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant (P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥ 39 °C);other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥ 39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases (P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases (OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively. © 2021 Chinese Medical Association. All rights reserved.

Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Efficacy and Safety Results of the Phase 3 Candor Study

Introduction: The randomized, open-label, multicenter, phase 3 CANDOR study compared carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in patients with multiple myeloma who have relapsed after 1-3 prior lines of therapy (ClinicalTrials.gov, NCT03158688). In the previously reported primary analysis (Dimopoulos et al, Lancet 2020), a significant progression-free survival (PFS) benefit was demonstrated in patients treated with KdD vs patients treated with Kd (hazard ratio [HR], 0.63 [95% CI, 0.46-0.85];two-sided P=0.0027). However, after a median follow-up of 16.9 months, median PFS was not reached in the KdD arm. Here, we report updated efficacy and safety outcomes from the CANDOR study. Methods: Adult patients with relapsed or refractory multiple myeloma (RRMM) received 28-day cycles of KdD or Kd (randomized 2:1). In the primary analysis, PFS was the primary endpoint and overall survival (OS) a key secondary endpoint. In this prespecified interim OS analysis, statistical testing was based on the actual number of OS events observed by the data cutoff (approximately 36 months after enrollment of the first patient);PFS was summarized descriptively. Disease progression was determined locally by investigators in an unblinded manner and centrally by the sponsor using a validated computer algorithm (Onyx Response Computer Algorithm [ORCA]) in a blinded manner. PFS and OS were compared between the KdD and Kd arms using a stratified log-rank test, and HRs were estimated by a stratified Cox proportional-hazards model. Results: Patients were randomized to KdD (n = 312) and Kd (n = 154). Of all randomized patients, median age was approximately 64 years;42% received previous lenalidomide, and 33% were lenalidomide refractory;90% received previous bortezomib, and 29% were bortezomib refractory. At the data cutoff date of June 15, 2020, 199 (63.8%) patients in the KdD arm and 88 (57.1%) in the Kd arm remained on study. Among patients treated with KdD and Kd, 140 (44.9%) and 85 (55.2%) had PFS events, respectively;median follow-up was 27.8 months (KdD) and 27.0 months (Kd). Median PFS by ORCA was 28.6 months for the KdD arm versus 15.2 months for the Kd arm (HR, 0.59 [95% CI, 0.45-0.78];Figure). OS data were not mature and will be updated at a future prespecified analysis. Median treatment duration was 79.3 weeks with KdD versus 40.3 weeks with Kd. Grade ≥3 adverse events (AEs) occurred in 87.0% and 75.8% of patients in the KdD and Kd arms, respectively, and fatal AEs occurred in 8.8% and 4.6%;one fatal AE in the KdD arm (due to arrhythmia) and one fatal AE in the Kd arm (due to COVID-19 pneumonia) had occurred since the primary analysis. Carfilzomib treatment discontinuation rates due to AEs were 26.0% with KdD and 22.2% with Kd. Exposure-adjusted AE rates per 100 patient years were: 171.2 and 151.9 for grade ≥3 AEs and 6.9 and 5.6 for fatal AEs in the KdD and Kd arms, respectively. Updated data by key subgroups will be presented. Conclusion: With approximately 11 months of additional follow-up, a 13.4-month improvement in median PFS was observed in patients treated with KdD (28.6 months) versus patients treated with Kd (15.2 months;HR, 0.59 [95% CI, 0.45-0.78]). Safety was consistent with previously reported results. KdD continues to show a favorable benefit-risk profile and represents an efficacious treatment option for patients with RRMM. [Formula presented] Disclosures: Dimopoulos: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;Celgene: Consultancy, Ho oraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau. Quach: GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy;Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees;Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding;GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria. Mateos: EDOMundipharma: Consultancy;Adaptive: Consultancy;Pharmamar: Consultancy;GlaxoSmithKline: Consultancy;AbbVie: Consultancy;Takeda: Consultancy;Amgen: Consultancy;Celgene: Consultancy;Janssen: Consultancy. Landgren: Pfizer: Consultancy, Honoraria;Merck: Other;Cellectis: Consultancy, Honoraria;Juno: Consultancy, Honoraria;Glenmark: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria;Binding Site: Consultancy, Honoraria;Celgene: Consultancy, Honoraria, Research Funding;Pfizer: Consultancy, Honoraria;Karyopharma: Research Funding;Merck: Other;Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Glenmark: Consultancy, Honoraria, Research Funding;Juno: Consultancy, Honoraria;Seattle Genetics: Research Funding;Cellectis: Consultancy, Honoraria;Seattle Genetics: Research Funding;Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding;BMS: Consultancy, Honoraria;Adaptive: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Binding Site: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Karyopharma: Research Funding. Leleu: Incyte: Honoraria;Merck: Honoraria;Novartis: Honoraria;Amgen: Honoraria;GSK: Honoraria;Sanofi: Honoraria;BMS-celgene: Honoraria;Janssen: Honoraria;Oncopeptide: Honoraria;AbbVie: Honoraria;Carsgen: Honoraria;Karyopharm: Honoraria. Siegel: Janssen: Consultancy, Honoraria, Speakers Bureau;Merck: Consultancy, Honoraria, Speakers Bureau;Amgen: Consultancy, Honoraria, Speakers Bureau;Celulatiry: Consultancy;Karyopharma: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Speakers Bureau;BMS: Consultancy, Honoraria, Speakers Bureau. Weisel: Takeda: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Karyopharm: Consultancy, Honoraria;Adaptive: Consultancy, Honoraria;Bristol-Myers Squibb: Consultancy, Honoraria;GlaxoSmithKline: Honoraria;Sanofi: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria;Roche: Consultancy, Honoraria. Gavriatopoulou: Takeda: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Genesis Pharma: Consultancy, Honoraria;Karyopharm: Consultancy, Honoraria;Amgen: Consultancy, Honoraria. Oriol: Janssen: Consultancy;Celgene: Consultancy, Speakers Bureau;Amgen: Consultancy, Speakers Bureau. Rabin: Janssen, BMS/Celgene, Takeda, Karyopharm, Amgen: Consultancy;Janssen, BMS/Celgene, Takeda: Other: Travel;Jansse, BMS/Celgene, Takeda: Speakers Bureau. Nooka: GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding;Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding;Spectrum Pharmaceuticals: Consultancy;Celgene: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;Oncopeptides: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria;Adaptive Technologies: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Research Funding. Ding: Amgen: Current Employment. Zahlten-Kumeli: Amgen: Current Employment, Current equity holder in publicly-traded compan . Usmani: Celgene: Other;GSK: Consultancy, Research Funding;Pharmacyclics: Research Funding;Array Biopharma: Research Funding;Seattle Genetics: Consultancy, Research Funding;Merck: Consultancy, Research Funding;Incyte: Research Funding;SkylineDX: Consultancy, Research Funding;Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy;BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding.