ABSTRACT
Case Report: It is well documented that Coronavirus Disease 19 (COVID-19) patients who suffer cardiac injury have a higher mortality rate, however the exact mechanism of cardiac injury and potential complications are still unknown. Takotsubo Cardiomyopathy (TCM), which was first described in 1990 in Japan, is characterized by a transient systolic and diastolic left ventricular dysfunction with a range of wall motion abnormalities predominantly affecting women often following an emotional or physical trigger. Though TCM is seen less commonly as a cardiac complication of COVID-19, with increasing rates of cardiovascular events due to COVID-19, TCM should be taken into consideration as a potential diagnosis for a COVID-19 positive patient. Case Description: The case of a 75-year old female with a history significant for hypertension, type 2 diabetes mellitus, hyperlipidemia, and gastroesophageal reflux disease presented to the Emergency Department after a ground level fall and subsequent left hip pain. Upon primary survey, EKG showed persistent sinus tachycardia in the 130-150s, with intermittent borderline dynamic changes and a troponin that was mildly elevated at 0.10, and an initial false negative COVID-19 test. Preoperative echocardiogram showed normal left ventricle size, no regional wall abnormalities, and a left ventricular ejection fraction (LVEF) of 60-65%. In post-operative care, EKG illustrated dynamic changes in the form of ST elevation in the lateral precordial leads, as well as an increase in the cardiac troponins, from 0.07 to 3.51. A subsequent echocardiogram illustrated a drop in her ejection fraction from 60-65% to 30-35%, with evidence of left ventricular systolic dysfunction that was not noted on previous echocardiograms. Following the Mayo clinic diagnostic criteria, this patient met the diagnostic criteria for TCM, as evident by new electrocardiograph findings, non-obstructive cardiac catherization findings, echocardiogram findings illustrating transient left ventricular systolic dysfunction, modest elevations in cardiac troponins as well as the patient being a post-menopausal female. Subsequent echocardiogram on 2 week follow up showed a rebound in her ejection fraction to 50-55%. Discussion(s): Possible outcomes of TCM include cardiogenic shock, respiratory failure, and death. It is imperative that clinicians consider TCM as a possible diagnosis when treating COVID-19 patients that may be exhibiting cardiac complications. Frequent ECG monitoring and a vigilant differential should include TCM in patients presenting with COVID-19.
ABSTRACT
Background: Given the paucity of data on safety and effectiveness of mRNA COVID-19 booster vaccinations in lower income settings with high HIV prevalence, we evaluated a heterologous mRNA-1273 (Moderna) boost after priming with 1 or 2 doses of Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine among health care workers (HCWs) in South Africa. Method(s): SHERPA is an open-label, phase 3 mRNA-1273 booster study, nested in the Sisonke Phase 3b implementation trial, that vaccinated ~500000 HCWs with 1 or 2 doses of Ad26.COV2.S from Feb and Dec 2021. Sisonke participants were offered mRNA-1273 boosters between 23 May and 12 Nov 2022 (median 17 and 8 months after 1 and 2 Ad26.COV2.S, respectively), with data cut-off on 12 Dec 2022. Reactogenicity and adverse events (AEs) were self-reported via an online data entry link shared by SMS with participants 1, 7 and 28 days after boosting. Using national databases analyses are underway to compare effectiveness against COVID-19 infections and severe disease with Sisonke participants who did not receive the booster. Result(s): 12188 HCWs (79.5% female, 28.6% with self-reported previous COVID-19 diagnosis) received a mRNA-1273 booster, of whom 44.6% and 55.4% had received 1 and 2 prior Ad26.COV2.S vaccines in Sisonke, respectively. 3056 (25.2%) reported being HIV positive, more among those receiving only 1 previous Ad26.COV2.S (26.8% vs 23.9%), and 1.4% reported not being on antiretroviral therapy. 17.0% of participants reported hypertension and 6.4% diabetes mellitus. 262 participants (2.1% of women, 2.5% of men) reported 234 reactogenicity events and 95 AEs post-vaccination, with more reported by those with prior COVID-19 infection (3.5% vs 1.6%), HIV negative status (2.5% vs 1.2%) and those who received 2 prior doses of Ad26.COV2.S (2.4% vs 1.8%) (Table). Among 159 (1.3%) reporting injection site reactions the commonest were pain (59.7%), swelling (42.1%) and induration (20.1%). Of 177 (1.5%) systemic reactogenicity events (all grade 1 or 2 severity), the commonest were myalgia (69.5%), headache (67.8%) and fever (37.9%). 14 participants had AEs of special interest or serious AEs, of which 4 (all AESIs of ageusia or anosmia) were deemed related to the booster. 13 COVID-19 infections occurred a median of 125 days post booster vaccination (IQR 90-154) after 3477 person-years of follow up. Conclusion(s): A mRNA-1273 booster administered after 1 or 2 doses of Ad26. COV2.S was well tolerated regardless of HIV status, other chronic conditions or prior COVID-19 infection.
ABSTRACT
Calcium levels in the Coronary Artery are an indicative marker of the presence and extent of atherosclerosis. This serves as an additional prognostic indicator in addition to traditional risk factors. Moreover, the coronary calcium test is associated with a descriptor known as the calcium score or calcium score (Cs), which is primarily useful for stratifying the risk of asymptomatic patients, while for patients with acute or chronic chest pain, coronary axial computed tomography is generally required. A retrospective analysis of data was conducted in the radiology department of King Salman Specialist Hospital in Hail City, the kingdom of Saudi Arabia, between January and May 2022. A total of 40 patients were randomly selected, 25 males and 15 females. The study included all patients with or suspected of having a calcium deposit who underwent a CT scan using the Siemens SOMATOM definition MDC scan. Patients underwent a scan with the preparations and laboratory tests required for their coronary artery calcium scores. In this study, males were more likely to be affected by calcium deposits (64%), whereas females were 36%. Approximately 50 percent of the study populations were found to be normal (no identifiable calcium deposits) and 37.5% to have moderate calcium deposits. There is a significant association between CACS and moderate CVD risks based on age and gender in this study. Better control of cardiovascular system (CVS) risks is recommended in all primary care centers in the Kingdom of Saudi Arabia (KSA).Copyright © 2022 International Journal of Pharmaceutical Research and Allied Sciences. All rights reserved.
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Background: Telemedicine based on wearable intelligent health devices becomes increasingly promissing for the elderly due to the accelerated aging population. Especially during COVID-19 pandemic, more elderly coronary heart disease patients with chronic comorbidities are in less secondary prevention management at home. Objective(s): To explore the prevention effect on main cardiovascular risk factors and repeated hospitalization in elderly comorbidities patients by telemedicine intervention based on multi-parameter wearable monitoring devices. Method(s): Total of 337 patients with comorbidities of coronary heart disease, hypertension and diabetes, with age more than 65 years old were recruited in the study from October 2019 to January 2021. They were randomly divided into control group and telemedcine intervention group. The latter used remote multi-parameter wearable devices to measure blood pressure, glycemic and electrocardiograph at home every day. A real-time monitoring platform would alarm any abnormal data to the doctors. Both doctors and patients can read the measurement results on a real-time mobile phone APP and interact with each other remotely twice a week routinely. A medical team remotely indicated the medications, while offering guidance on lifestyle. In contrast, the control group adopted traditional outpatient medical strategy to manage diseases. Result(s): A total of 306 patients were enrolled in the follow-up experiment finally: 153 in the intervention group and 153 in the control group. Patient characteristics at baseline were balanced between two groups. After 12 months, compared with the control group, the intervention group saw the following metrics significantly reduced: Systolic blood pressure (SBP) (131.66+/-9.43 vs 137.20+/-12.02 mmHg, P=0.000), total cholesterol (TC) (3.65+/-0.79 vs 4.08+/-0.82 mmol/L, P=0.001), low density lipoprotein cholesterol (LDL-C) (2.06+/-0.53 vs 2.38+/-0.61 mmol/L, P=0.002), and fasting blood glucose (FBG) (6.26+/-0.75 vs 6.81+/-0.97 mmol/L, P=0.000), while the following metrics went up significantly: Blood pressure control rate (77.3% vs 59.1%, P=0.039), blood lipid control rate(39.4% vs 21.2%, P=0.037), glycemic control rate (71.2% vs 51.5%, P=0.031), and medication adherence score (7.10+/-0.77 vs 6.80+/-0.73, P=0.020). Linear regression model analysis indicates that when interaction frequency >=1.53, 2.47 and 1.15 times/week, the SBP, LDL-C and FBG levels would be controlled, respectively. Cox survival analysis finds that the hospitalization rate of intervention group is significantly lower than that of the control group (24.18% vs 35.29%, P=0.031). Conclusion(s): The telemedicine interactive intervention based on multiparameter wearable devices provides effectively improvement of cardiovascular risk controlling, medication adherence, while reducing the hospitalization rate of patients. A frequency of doctor-patient interactions more than 2 times/week is beneficial for disease management the elderly at home. (Figure Presented) .
ABSTRACT
Introduction: Kidney transplant recipients (KTRs) are at risk for substantial morbidity and mortality during COVID-19 infection. Vaccination for this group of patients is reccommended. However, immunogenicity and safety data after COVID-19 vaccination among KTRs remains limited. Method(s): We conducted an observational prospective trial involving KTRs at Chiang Mai University hospital, Chiang Mai, Thailand. The participants were received homologous ChAdOx1 nCoV-19 (AZ-AZ), or the heterologous prime-boost of CoronaVac,followed by AZ (SV-AZ). The immunogenicity was assessed by measuring antibodies against the S1 receptor-binding domain (anti-RBD), and SARS-CoV-2 surrogate virus neutralization test (sVNT) at specific timepoints. The primary outcome was the seroconversion rate of sVNT at day 28 after complete vaccination. The secondary outcomes were the seroconversion rate of sVNT at day 28 after the first dose of vaccination, the level of sVNT and anti-RBD at specific timepoints, and the adverse events of each vaccine regimen. Result(s): A total of 18 KTRs were recruited. Among those, 13 (72.2%), and 5 (27.8%) patients were received AZ-AZ, and SV-AZ regimen, respectively. The seroconversion rate of sVNT at day 28 after the second dose were 23.1%, and 20.0% for AZ-AZ, and SV-AZ, respectively (P>0.99). The level of sVNT and the level of anti-RBD at day 28 after the first and at day 28 after the second dose were not different between groups (Figure 1). There were no serious adverse events reported in any vaccine groups. However, AZ-AZ showed sign of tubular dysfunction demonstrated by increasing of fractional excretion of magnesium after complete course of vaccination which correlated to the trend of urine albumin and urine protein creatinine ratio (r=0.720, P=0.013;and r=0.726, P=0.011, respectively). [Formula presented] [Formula presented] Figure 1 Percentage of neutralization inhibition (a) and level of anti-RBD antibody (b) at each visit of homologous ChAdOx1 nCoV-19 (AZ-AZ), and heterologous prime-boost of CoronaVac, followed by AZ (SV-AZ) regimen Conclusion(s): Immunogenicity after COVID-19 vaccination with either homologous or heterologous prime-boost regimen among KTRs was compromised. Homologous replication-defective viral vectors vaccine regimen seemed to affect renal tubular function, and further follow-up should be warranted. No conflict of interestCopyright © 2023
ABSTRACT
Background: In the year earlier part of 2020, many scientists urged to discover novel drugs against for the treatments of COVID-19. Coronavirus Disease 2019 (COVID-19), a life-threatening viral disease, was discovered first in China and quickly spread throughout the world. Objective(s): In the present article, some novel chalcone substituted 9-anilinoacridines (1a-z) were developed by in silico studies for their COVID19 inhibitory activity. Molecular docking studies of the ligands 1a-z were performed against COVID19 (PDB id-5R82) targeting the coronavirus using Schrodinger suite 2019-4. Method(s): The molecular docking studies were performed by the Glide module and the binding energy of ligands was calculated using the PRIME MM-GB/SA module of Schrodinger suite 2019-4. Result(s): From the results, many compounds are significantly active against COVID19 with a Glide score of more than-5.6 when compared to the currently used drug for the treatment of COVID19, Hy-droxychloroquine (-5.47). The docking results of the compounds exhibited similar mode of interactions with COVID19 and the residues, THR25, THR26, LEU27, SER46, MET49, HIE41, GLN189, ARG188, ASP187, VAL186, HIE164, ASN142, and GLY143 play a crucial role in binding with ligands. MM-GBSA binding calculations of the most potent inhibitors are more stably favourable. Conclusion(s): From the results of in-silico studies, it provides strong evidence for the consideration of valuable ligands in chalcone substituted 9-anilinoacridines as potential COVID19 inhibitors and the compounds, 1x,a,r,s with significant Glide scores may produce significant COVID19 activity for further development, which may prove their therapeutic potential.Copyright © 2020 Bentham Science Publishers.
ABSTRACT
Introduction/Background: Chronic pain is persistent pain lasting more than three months, impacting many aspects of a person's life. 20- 30% of UK adolescents experience chronic pain (although studies vary greatly). The previous pathway through our service was unclear, which meant young people were not accessing all available resources or being seen promptly. We aimed to create a model that optimised available resources, including local networks and ensured equitable access to our service across the region. We wanted to target critical barriers such as mental health, school attendance and sleep, and delivering asset-based care. Description/Method: We followed the plan, do, study, act PDSA cycle for this quality improvement project (QIP). The initial evaluation involved multidisciplinary team (MDT) meetings, site visits, and the MDT experience using other models of care. Patient cases were reviewed for weaknesses in existing models. Discussions highlighted the need to match resources to needs instead of a onesize- fits-all approach. Changes include creating our own model for Chronic Pain, introducing a specialist physiotherapy Triage Clinic to the pathway, converting our Pain Education Workshop (PEW) to virtual and utilising local resources by expanding our network. PEW seeks to empower patients and families to understand their pain. It is also offered to local healthcare professionals to increase confidence in supporting patients. We adapted the Thrive Mental Health Model to create a Triaged Model for Chronic Pain. We needed to streamline the service, as some patients became lost within the original pathway, not attending PEW and being on long waiting lists. We needed to manage difficulties faced with an increased patient cohort and case complexity, including mental health. Feedback demonstrated some patients found it difficult coming to MDT appointments without knowing who would be present. Triage Clinic helped to mitigate this. Young people with a lower level of need can be assessed virtually, have symptoms validated, receive advice and be discharged to appropriate care. Those with pain not managed by this reassurance are assessed within our service including, One-Stop-Shop, Adolescent Clinic for Rheumatology patients and Biomechanical clinic. Those requiring more support are referred to the MDT for intervention and education for serial day-case rehabilitation or more intensive intervention (PRIME). Ongoing challenges, such as severe mental health difficulties, mean some may not be ready to access support. We liaise with local services such as CAMHS, and patients may be reintroduced to the team later if appropriate. Discussion/Results: Our model showed improved outcomes compared to our previous service. We looked at data from 2018-2019 and 2021, removing the years involving the initial waves of the pandemic as the service adapted to the changes this brought. The physiotherapy Triage Clinic utilised our new Triage Model for the service. Following this we can discharge a portion of our patients to other services, some remain under the physiotherapy team, and the majority are seen in the Chronic Pain MDT clinic. It has been an opportunity, on initial consultation, to engage YP and their families and validate their pain. 22% of our patients had full school attendance on their initial review by our team. The average was a 59% attendance. There was an increase in 83% of those with initially reduced attendance following intervention with the chronic pain team. On average, attendance went from 44% to 71%. We saw a rise in the number of local services involved with young people under our care. Other services involved safeguarding teams, allied healthcare professionals and CAMHS teams. In 2018 on average, 1.4 services were involved;this increased to 1.8 in 2019 and 2.4 in 2021. This may be due to increased complexity of the cases we see or due to more local support requirements. Our plans following the MDT clinic increasingly show more specific goals and activities of daily living targets year on year, from 53% in 2018 to 0% having this as part of their plan in 2021. There have been regional development over the past three years of the service. We now have over 100 staff, including 43 local physiotherapists working collaboratively with our team in supporting the young people and their parents in our care. The Evelina team aims to lead regional meetings and communities of practice. Key learning points/Conclusion: With the limited available resources, our team is continuing to work towards managing a complex cohort of patients successfully. We were shortlisted for a British Society of Rheumatology Award for Best Practice following the changes made within our department. This QIP and our new model can be adapted to many other specialities and teams. Changes we have made are especially relevant following the impacts of the Covid-19 pandemic and continued pressure with reduced resources and increased demand. The virtual PEW allows for increased access for young people that previously struggled to attend face-to-face workshops in a timely fashion. The young people and their families benefit from improving their understanding of their pain and learning new strategies to manage it. Some patients find the virtual setting more practical as they miss less school and do not have to pay for costly transport to attend. Others miss the face-to-face interaction with peers who have similar difficulties. Both individual peer support and expert patients are areas we would like to explore as a service allowing the ripple effect of our model to continue. While improving the efficiency of some aspects of our service, we know that a further challenge is managing other 'bottle necks' created. From this conference, we hope our new model will be critically appraised and answer questions from our peers in other services. We look forward to learning from the experience of our colleagues who also work with this often complex cohort of patients.
ABSTRACT
Introduction/Background: Chronic pain is persistent pain lasting more than three months, impacting many aspects of a person's life. 20- 30% of UK adolescents experience chronic pain (although studies vary greatly). The previous pathway through our service was unclear, which meant young people were not accessing all available resources or being seen promptly. We aimed to create a model that optimised available resources, including local networks and ensured equitable access to our service across the region. We wanted to target critical barriers such as mental health, school attendance and sleep, and delivering asset-based care. Description/Method: We followed the plan, do, study, act PDSA cycle for this quality improvement project (QIP). The initial evaluation involved multidisciplinary team (MDT) meetings, site visits, and the MDT experience using other models of care. Patient cases were reviewed for weaknesses in existing models. Discussions highlighted the need to match resources to needs instead of a onesize- fits-all approach. Changes include creating our own model for Chronic Pain, introducing a specialist physiotherapy Triage Clinic to the pathway, converting our Pain Education Workshop (PEW) to virtual and utilising local resources by expanding our network. PEW seeks to empower patients and families to understand their pain. It is also offered to local healthcare professionals to increase confidence in supporting patients. We adapted the Thrive Mental Health Model to create a Triaged Model for Chronic Pain. We needed to streamline the service, as some patients became lost within the original pathway, not attending PEW and being on long waiting lists. We needed to manage difficulties faced with an increased patient cohort and case complexity, including mental health. Feedback demonstrated some patients found it difficult coming to MDT appointments without knowing who would be present. Triage Clinic helped to mitigate this. Young people with a lower level of need can be assessed virtually, have symptoms validated, receive advice and be discharged to appropriate care. Those with pain not managed by this reassurance are assessed within our service including, One-Stop-Shop, Adolescent Clinic for Rheumatology patients and Biomechanical clinic. Those requiring more support are referred to the MDT for intervention and education for serial day-case rehabilitation or more intensive intervention (PRIME). Ongoing challenges, such as severe mental health difficulties, mean some may not be ready to access support. We liaise with local services such as CAMHS, and patients may be reintroduced to the team later if appropriate. Discussion/Results: Our model showed improved outcomes compared to our previous service. We looked at data from 2018-2019 and 2021, removing the years involving the initial waves of the pandemic as the service adapted to the changes this brought. The physiotherapy Triage Clinic utilised our new Triage Model for the service. Following this we can discharge a portion of our patients to other services, some remain under the physiotherapy team, and the majority are seen in the Chronic Pain MDT clinic. It has been an opportunity, on initial consultation, to engage YP and their families and validate their pain. 22% of our patients had full school attendance on their initial review by our team. The average was a 59% attendance. There was an increase in 83% of those with initially reduced attendance following intervention with the chronic pain team. On average, attendance went from 44% to 71%. We saw a rise in the number of local services involved with young people under our care. Other services involved safeguarding teams, allied healthcare professionals and CAMHS teams. In 2018 on average, 1.4 services were involved;this increased to 1.8 in 2019 and 2.4 in 2021. This may be due to increased complexity of the cases we see or due to more local support requirements. Our plans following the MDT clinic increasingly show more specific goals and activities of daily living targets year on year, from 53% in 2018 to % having this as part of their plan in 2021. There have been regional development over the past three years of the service. We now have over 100 staff, including 43 local physiotherapists working collaboratively with our team in supporting the young people and their parents in our care. The Evelina team aims to lead regional meetings and communities of practice. Key learning points/Conclusion: With the limited available resources, our team is continuing to work towards managing a complex cohort of patients successfully. We were shortlisted for a British Society of Rheumatology Award for Best Practice following the changes made within our department. This QIP and our new model can be adapted to many other specialities and teams. Changes we have made are especially relevant following the impacts of the Covid-19 pandemic and continued pressure with reduced resources and increased demand. The virtual PEW allows for increased access for young people that previously struggled to attend face-to-face workshops in a timely fashion. The young people and their families benefit from improving their understanding of their pain and learning new strategies to manage it. Some patients find the virtual setting more practical as they miss less school and do not have to pay for costly transport to attend. Others miss the face-to-face interaction with peers who have similar difficulties. Both individual peer support and expert patients are areas we would like to explore as a service allowing the ripple effect of our model to continue. While improving the efficiency of some aspects of our service, we know that a further challenge is managing other 'bottle necks' created. From this conference, we hope our new model will be critically appraised and answer questions from our peers in other services. We look forward to learning from the experience of our colleagues who also work with this often complex cohort of patients.
ABSTRACT
In this paper, a preliminary implementation of a system monitoring the fetus's heart rate (FHR) has been designed and implemented as a mobile wearable measuring system with remote sensing specifically developed on Node MCU ESP8266 (ESP). In particular, the proposed system uses sensors for heart rate, humidity, temperature, and a transceiver module. The transceiver module is capable of efficient data transmission to a remote server station using an IEEE 802.11 b/g/n protocol - based on the wireless network. A major benefit is that the patient's data is monitored at distance using an IoT device. Hence, it complies with the health safety distance measures required due to various situations, including that of the COVID-19 pandemic. The proposed implementation has been proven to be efficient in terms of hardware simplicity and cost-effectiveness and is accompanied by preliminary accurate measurements of the FHR. © 2022 IEEE.
ABSTRACT
Background: In the Phase 3 POSEIDON study, 1L T+D+CT demonstrated statistically significant improvements in PFS and OS (OS HR 0.77;95% CI 0.65-0.92;p=0.0030;mFU 34.9 mo in censored pts) vs CT alone in pts with mNSCLC. D+CT showed a statistically significant improvement in PFS and a positive trend for OS improvement vs CT that did not reach significance (OS HR 0.86;95% CI 0.72-1.02;p=0.0758). Here we report an updated exploratory analysis of OS, and histology and mutational status subgroups, after a mFU of ~4 y. Method(s): Pts with EGFR/ALK wild-type mNSCLC were randomised 1:1:1 to 1L D (until progression) +/- limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles);or CT (up to 6 cycles). Alpha-controlled endpoints were PFS and OS for D+CT vs CT and T+D+CT vs CT. Pt tumours were molecularly characterised via sequencing of tissue and/or ctDNA samples. Result(s): At an updated data cutoff (DCO) of 11 Mar 2022 (mFU 46.5 mo in censored pts), T+D+CT continued to show OS benefit vs CT (HR 0.75;95% CI 0.63-0.88) with an estimated 25.0% of pts alive at 3 y vs 13.6% (Table). D+CT continued to numerically improve OS vs CT (HR 0.84;95% CI 0.71-0.99;3 y OS 20.7%). Consistent with results at the earlier DCO, OS benefit appeared more pronounced with T+D+CT vs CT in pts with non-squamous (than squamous;data will be presented) histology. A trend for OS benefit with T+D+CT vs CT continued to be observed in non-squamous subgroups with mutations (m) in STK11 (Table), KEAP1 or KRAS (data will be presented). No new safety signals were identified based on collection of serious AEs during long-term FU. [Formula presented] Conclusion(s): The results of this exploratory analysis from POSEIDON, after mFU of ~4 y, demonstrate the durable long-term OS benefit of adding a limited course of T to D and 4 cycles of CT. These data support the use of this regimen as a 1L treatment option for pts with mNSCLC, including harder-to-treat mutational subgroups such as STK11m, KEAP1m or KRASm. Clinical trial identification: NCT03164616 (release date: 23 May 2017). Editorial acknowledgement: Medical writing support for the development of this , under the direction of the authors, was provided by James Holland, PhD, of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca PLC. Funding(s): AstraZeneca. Disclosure: B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc;Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp., J INTS BIO;Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp, J INTS BIO;Financial Interests, Personal, Royalties: Champions Oncology;Financial Interests, Personal, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp;Financial Interests, Personal, Advisory Role, Consulting: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines;Financial Interests, Personal, Other: DAAN Biotherapeutics. J.A. Alatorre Alexander: Financial Interests, Personal, Speaker's Bureau: BMS, Roche, AstraZeneca, MSD, Boehringer Ingelheim, Takeda, Eli Lilly, Janssen;Financial Interests, Personal, Advisory Board: BMS, Roche, AstraZeneca, MSD, Boehringer Ingelheim, Takeda, Eli Lilly, Janssen. S. Lucien Geater: Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Institutional, Principal Investigator: AstraZeneca, Roche, Novartis, Boehringer Ingelheim;Financial Interests, Personal, Advisory Role: Pfizer. K. Sang-We: Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim;Financial I terests, Personal, Research Grant: Yuhan;Non-Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Boehringer Ingelheim, Norvatis, Lilly, Takeda, Therapex, and Yuhan. M. Hussein: Financial Interests, Personal, Advisory Board: AbbVie, Aptitude Health, AstraZeneca, Biopahrama, BMS, Exelixis, Mirati Therapeutics, Cardinal Health, Coherus Biosciences, Athenex, Karyopharm Therapeutics, IntegraConnect, Oncocyte. C.T. Yang: Financial Interests, Personal, Principal Investigator: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Merck, Amgen, Johnson & Johnson, AbbVie, Hanso Pharma, Roche, Ono, BMS, Chugai. L.H. Araujo: Financial Interests, Personal, Invited Speaker: MSD, Roche, Pfizer, AstraZeneca, Takeda, Lillly, Janssen, Amgen, Novartis, BMS, Sanofi;Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, AstraZeneca, Sanofi. H. Saito: Financial Interests, Personal, Speaker's Bureau: AstraZeneca, ONO Pharmaceutical;Financial Interests, Personal, Principal Investigator: AstraZeneca, Chugai Pharmaceutical ONO Pharmaceutical, Bristol Myers Squibb. N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Hoffmann-La Roche, Janssen, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Other: Symphogen: Data Safety Monitoring Board. Z. Lai, H. Mann, X. Shi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca;Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure;Financial Interests, Institutional, In ited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati;Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier;Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca;Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca;Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS;Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS;Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene;Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK;Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD;Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati;Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar;Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics;Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01;chair ALEX;steering committee BFAST;steering committee BEAT-Meso;steering committee ImPower-030, IMforte: Roche/Genentech;Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos;Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO;Non-Financial Interests, Personal, Officer, Council Me ber & Scientific Committee Chair: ETOP/IBCSG Partners;Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK;Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities;Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Bejart Lausanne Foundation;Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK;Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR;Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO;Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK;Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO;Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. E.B. Garon: Financial Interests, Personal, Advisory Board: ABL Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, Eisai, Eli Lilly, EMD Serono, Gilead, GSK, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, Xilio Therapeutics;Financial Interests, Personal, Research Grant: ABL Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, EMD Serono, Genentech, Iovance Biotherapeutics, Eli Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, Novartis. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, BI, BMS, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communication, Janssen Pharmaceutica NV, Jiahui Holdings Co. Limi, Novartis, OrigiMed Co. Ltd., P. Permanyer SL, PeerVoice, Physicians' Education Resource, Pfizer, PrIME Oncology, Research to Practice, RochePharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd., T;Financial Interests, Personal, Advisory Board: AbbVie Inc., ACEA Pharma, Amgen, AstraZeneca, Berry Oncology, Blueprint Medicines Corporation, Boehringer Ingelheim Pharmaceuticals Inc., Bristol Myers Squibb Company, C4 Therapeutics, Inc, Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lily, Loxo-Oncology Inc., Lunit, Inc., Mer k Serono, Merck Sharp & Dohme, Mirati Therapeutics, Inc., MiRXES Group, Novartis, OrigiMed, Pfizer, Puma Biotechnolo;Financial Interests, Personal, Member of the Board of Directors: AstraZeneca PLC, HutchMed;Financial Interests, Personal, Full or part-time Employment: The Chinese University of Hong Kong (Full-Time);Financial Interests, Personal, Stocks/Shares: Aurora Tele-Oncology Ltd., HutchMed, Act Genomics-Sanomics Group, Loxo-oncology, Virtus Medical Group and Lunit USA, Inc;Non-Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery;Financial Interests, Personal, Leadership Role: Lunit USA, Inc., ACT Genomics-Sanomics Group, Aurora;Financial Interests, Personal, Other, Independent contractor: AbbVie Inc., ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, Berry Oncology, BI, Blueprint Medicines Corporation, BMS, C4 Therapeutics, Inc, CStone Pharmaceuticals, Curio Science, Daiichi Sa, Loxo-Oncology, Merck Serono, MSD, Mirati Therapeutics Inc., MoreHealth, Novartis, OrigiMed, Pfizer, Puma Biotechnology Inc., Qiming Development (HK) Ltd., Roche Pharmaceuticals, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Takeda Pharmaceuticals HK Ltd., Vert, Guardant Health, Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lilly, Lunit USA, Inc., Loxo-Oncology, Lucence Health Inc., Medscape LLC/ WebMD, Merck Serono, MSD, Mirati Therapeutics Inc., MiRXES, MoreHea. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie;Acerta;Adaptimmune;Amgen;Apexigen;Arcus B osciences;Array BioPharma;Artios Pharma;AstraZeneca;Atreca, BeiGene;BerGenBio;BioAtla;Boehringer Ingelheim, Calithera Biosciences;Checkpoint Therapeutics;Corvus Pharmaceuticals;Curis;CytomX, Daiichi Sanyo;Dracen Pharmaceuticals;Dynavax, Eli Lilly, Elicio Therapeutics, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan Kettering, Merck, Merus, Mirati Therapeutics, NeoImmuneTech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Pharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics;Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Eli Lilly, EMD Serono, G1 Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, IDEAYA Biosciences, iTeos, Janssen, Merck, Mirati Therapeutics, Novartis, Oncorus, Regeneron Pharmaceuticals, Revolution Medicines, Ribon Therapeutics, Sanofi, Turning Point Therapeutics, WindMIL. All other authors have declared no conflicts of interest. Copyright © 2022
ABSTRACT
Background: For rheumatoid arthritis (RA) patients, hydroxychloroquine (HCQ) is a staple treatment. Concerns about its cardiovascular safety have been raised after reports of its use and fatal arrhythmias in individuals with coronavirus illness 19. Aims and objectives: To examine the relationship between HCQ use and corrected QT (QTc) length in RA patients. Material(s) and Method(s): Hundred subjects (age >= 18 years) were studied after dividing them in to Cases (n=50;patients with RA taking HCQ) and Control (n=50;patients without RA not taking HCQ) at the Department of General Medicine of a tertiary care center in Madhya Pradesh. Patient characteristics and laboratory measures, including rheumatoid factor hemoglobin, white blood cells count, platelets, erythrocyte sedimentation rate (ESR), random blood sugar, urea, Creatinine, SGOT, SGPT, serum electrolytes, calcium, and magnesium level, were assessed. QTc length was obtained with the help of 12-lead ECG. Result(s): Incidence of QTc prolongation in patients with RA was 11%. Odds for prolonged QTc interval for patients with age >50 years was 3.500 (95% CI = 0.865-14.155), serum calcium <8 was 2.400 (95% CI = 0.540-10.666), and ESR >20 was 0.756 (95% CI = 0.640-0.892). A significant positive correlation was obtained between prolonged QTc with age (r=0.283;p=0.046). Conclusion(s): There is a significant increase in risk of QTc prolongation with the use of HCQ in patients with RA. Copyright © 2022, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.
ABSTRACT
Introduction: Limited data exist on the immunogenicity of SARS-CoV-2 vaccination in liver transplant (LT) recipients. Homologous vaccination protocol demonstrated suboptimal responses in this population. Several studies showed that heterologous prime-boost approach yielded a better seroconversion rate in healthy individuals. We, therefore, aimed to explore the immunogenicity and safety of heterologous prime-boost immunization with ChAdOx1 nCoV-19 AstraZeneca (AZ) and BNT162b2 Pfizer-BioNTech (BNT) among LT patients. Method: LT recipients receiving SARS-CoV-2 vaccine at King Chulalongkorn Memorial Hospital between April and November 2021 were consecutively enrolled. Patients received either heterologous prime-boost protocol (AZ/BNT) or homologous regimen (AZ/AZ) depending on national policies. Blood samples were collected before vaccine administration and 4 weeks after the second dose. SARS-CoV-2 spike receptor-binding-domain (RBD) IgG was measured using electrochemiluminescence immunoassay (Roche). A titer $100 U/mL was considered as a protective antibody. The neutralizing antibody was detected by enzymelinked immunosorbent assay-based surrogate virus neutralization test (sVNT) (GenScript) with positive cut-off of ≥30% inhibition. Adverse events (AEs) within 7 days following vaccination were recorded by questionnaires. Results: Eighty-nine LT recipients were enrolled. Of these, 64 (71.9%) and 25 (28.1%) patients received AZ/BNT and AZ/AZ, respectively. Majority was male (68.5%) with mean age of 58.3±14.5 years. Median time since transplant was 5.7 years (IQR 2.8-11.8). No patient had a previous diagnosis of SARSCoV- 2 infection. Comparable seroconversion rate of anti-RBD antibody and sVNT after vaccination were observed in both AZ/BNT and AZ/AZ groups (70.3% vs 64.0%, p=0.62 and 77.8% vs 59.1%, p=0.10, respectively). However, median IgG titer was significantly higher in AZ/BNT group compared to AZ/AZ group (842.9 U/mL vs 152.2 U/mL, p=0.011). Patients receiving AZ/BNT also had significantly higher sVNT levels than those receiving AZ/BNT (91.2% vs 35.8%, p=0.003) (Figure 1). In multivariate analysis, use of prednisolone (OR 6.3, 95%CI 1.1-35.4, p=0.036) and LT duration <5 years (OR 3.2, 95%CI 1.1-9.1, p= 0.029) were associated with lack of protective serological response. AZ/BNT regimen trended to have higher reported AEs than AZ/AZ (Figure 2). No graft rejection or serious AEs were found. Conclusion: Heterologous prime-boost regimen with adenoviral vectored and mRNA SARS-CoV-2 vaccine yielded greater humoral response than homologous protocol and was well-tolerated in LT recipients. T-cell response, which might play additional role in protection, and immune durability of this mix-and-match strategy are eagerly awaited. (Figure Presented)
ABSTRACT
Background: Asymptomatic patients with atrial fibrillation (AF) pose challenges to diagnosis. Early diagnosis can reduce morbidity and mortality. Systematic screening in primary care may result in early intervention. Objectives: We sought to examine the implementation outcomes of a systematic, team-based quality improvement education (QIE) intervention for AF screening in primary care during the COVID-19 pandemic. Methods: QIE intervention was implemented in academic-based (n=4) and community-based (n=2) practices to address COVID-19 challenges. Surveys administered by site identified existing approaches and provider teams developed screening protocol based on targeted education, deploying a mobile ECG device (Kardiamobile™). Patient charts were reviewed (Dec 2020-May 2021) to determine eligibility, i.e., patients aged 65-74 (with prior stroke/TIA or two other risk factors) or aged ≥75 (with one other risk factor) without prior AF. Patient EHR data were examined for demographic/clinical data and screening outcome. Provider interviews (n=12) and validation from representative patients (n=2) accounted for sustainability of outcomes. Results: A total of 1,221 patients were evaluated for AF risk, with 408 eligible for screening. Of these, 277 (68%) were female and CHA2DS2-VASc varied-score=3 (45%);score=4 (24%);score=5+ (31%). Patients (n=7;2%) who screened positive for AF were referred or started on anticoagulation, like other primary care studies. Figure 1 shows how systematic screening was re-imagined and implemented Satisfaction and engagement increased among providers and patients-attributed, in part, to benefits of team-based planning and targeted education. Conclusion: An AF screening program was adapted to improve patient care despite COVID-19 related challenges. A QIE toolkit was launched to assist primary care practices with implementing streamlined, sustainable, and patient-engaging strategies to reduce stroke.
ABSTRACT
Background: Currently available COVID-19 vaccination regimens in the US deliver either a homologous spike (S) mRNA prime-boost or a prime-only S DNA adenovirus-vectored antigen to elicit humoral and cell-mediated responses to confer protection against SAR-CoV-2 infection. Alternatively, heterologous vaccination using two different platforms has the potential to enhance and expand immune protection. Addition of a second SARS-CoV-2 antigen, the nucleocapsid (N) protein that is less subject to mutation and elicits vigorous T-cell responses, may also be advantageous. We report immunological responses to homologous and heterologous prime-boost vaccination regimens with a human DNA adenovirus serotype 5 S plus N (AdS+N) and/or a self-amplifying S-only mRNA vaccine (AAAH) delivered with a nanostructured lipid carrier (NLC). Methods: CD-1 mice received homologous or heterologous prime-boost combinations of AdS+N and AAAH. Priming doses were administered on Day 0, booster doses were delivered on Day 21, and mice were euthanized for blood and organ collection on Day 35. Serum was analyzed for anti-S (both wild type and variant) and anti-N IgG subtypes by ELISA. Spleen-resident CD4+ and CD8+ T cells were tested for IFN-γ, TNF-α, and IL-2 production in response to S-WT, S Delta variant and N protein overlapping peptides by intracellular cytokine staining (ICS). Splenocyte cytokine secretion upon stimulation with S-WT/N peptides was also assessed by IFN-γ and IL-4 ELISpot. Serum neutralization of the original Wuhan strain, Delta, and B.1.351 variants was assessed by a pseudovirus neutralization assay. Results: The highest humoral and T-cell responses were seen with the heterologous AAAH prime-AdS+N boost regimen, with a significant increase in T-cell responses relative to homologous vaccination. S protein-binding IgG was similar between wild type and Delta variant S proteins, with a strong/clear Th1/Th2 bias, and T cells responded to S wild type and S Delta peptides with similar levels of cytokine expression. Sera from AAAH prime-AdS+N boost mice showed the ability to neutralize Wuhan D614G, Delta, and B.1.351 (South Africa) variant pseudoviruses at high levels. Conclusion: Heterologous vaccination with the AAAH RNA vaccine prime and an AdS+N DNA boost may provide substantially improved humoral and cell-based immunity against SARS-CoV-2 variants by leveraging the advantages of each vaccine platform technology and by inclusion of immune responses to N.
ABSTRACT
Despite the many challenges faced in 2020, we have seen impressive progress in many areas of cancer research. Twenty-one novel oncology drugs were approved by the U.S. Food and Drug Administration (FDA). Although cancer is one of the major public health problems worldwide, cancer mortality projections for 2021 confirm the persistent declines in cancer mortality in EU and US for many specific cancers. The breast cancer treatment landscape has evolved in the past year and several new drugs approved in 2020 as antibody drugs conjugates (ADC) sacituzumab in TNBC and fam-trastuzumab deruxtecan-nxki (T-DXd) in metastatic HER2 positive BC, as well as tucatinib, a small kinase inhibitor. A few very important clinical trial /RxPONDER, ADAPT, PRIME II/ presented last year support de-escalation of adjuvant chemotherapy and radiation, sparing patients from some of the side effects that can accompany treatments. In ovarian cancer five-year follow-up data from the SOLO-1 trial continue to show progression-free survival benefit of olaparib as maintenance therapy following platinum-based chemotherapy in the frontline setting. In the final analysis of SOLO-2 trial, maintenance olaparib provided an improvement of 12.9 months in median OS vs placebo in women with relapsed BRCA-related ovarian cancer who had responded to their most recent platinum-based chemotherapy after having received at least one more line of chemotherapy.In 2020 first new treatment for hepatocellular carcinoma approved in more than ten years according to the data from phase III IMbrave 150 trial. In that study, which includes 501 patients the combination of atezolizumab and bevacizumab provides the longest survival seen in a front-line phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC.In the field of thoracic oncology there were some very important news in 2020, potentially practice changing. Osimertinib, next generation EGFR-TKI, standard first line therapy in metastatic EGFR-mutated advanced NSCLC was successfully used, in ADAURA study, in adjuvant setting vs placebo (planned treatment duration three years), in resected NSCLC patients, stage IB-IIIA. Patients might had adjuvant chemotherapy also, and there was no outcome differences between these two groups. Overall, there was a 79% reduction in the risk of disease recurrence or death (DFS HR was 0.21, p<0.0001). Lorlatinib is the third generation of ALKinhibitors in the treatment of advanced NSCLC. The results of CROWN study where lorlatinib was given in the first line treatment were presented at ESMO 2020. In this randomized study, comparing lorlatinib with crizotinib, lorlatinib was superior in the term of PFS, HR was 0.28, p<0.001, this superiority was particularly pronounced in intracranial disease, where the percent of intracranial response was 82% in lorlatinib arm and only 23% in crizotinib arm, and percent of complete response per CT was 71% vs 7%. Lorlatinib has been recently approved for patients with advanced ALK-positive NSCLC, irrespectively of treatment line. Also of interest were two studies that inovatively used immunologic drugs as a combination in advanced NSCLC: in Check Mate 9LA randomized study, cytotoxic chemotherapy was given in paralell with nivolumab + ipilimumab for first two cycles, and compared with four cycles of chemoherapy. Median OS was significantly better: 15.6 vs 10.9 months, HR 0.66 and a overall response rate was 38% vs 25%. CITYSCAPE study give us inovative combination of two immuno-oncology drugs, tiragolumab as TIGIT inhibitor, and standard atezolizumab. Median PFS was particularly longer in the population of patients with high PD-L1 expression (NE vs 4.11 months, HR 0.30). In gastrointestinal oncology, last year will be remembered by introducing immunotherapy in first line treatment of metastatic colorectal cancer for patients with MSI-H tumors. In KN177, such patients were randomized to receive pembrolizumab or standard chemotherapy+/-biologic therapy, and after second interim analysis, there was a ery clear adventage for pembrolizumab in terms of mPFS (16.5 vs 8.2 months) and duraton of response (at 24 months, 83% vs 35%). The results are impressive, and it is for expected to be confirmed by OS adventage in future analyses. In urological oncology, JAVELIN Bladder 100 study demonstrated that the maintenance avelumab + best supportive care is superior over best supportive care alone after platinum-based first-line chemotherapy in advanced urothelial carcinoma. In overall population, OS was 21.4 vs 14.3 months, HR 0.69, p<0.001, and the results are even better in PD-L1 positive population, with HR 0.56. These results are very probably practice changing, since cytotoxic chemotherapy have very modest achievements in the field of urothelial cancer.
ABSTRACT
Cardiac arrhythmias are common in patients of COVID -19 and frequently complicate the clinical course of critically ill patients. Life threatening arrhythmia including ventricular fibrillation less common but are reported to be more common in patients with elevated cardiac troponins. The mechanisms of arrhythmia in COVID 19 are multifactorial and arise from either direct cardiac involvement, from consequences systemic affection or drug interactions. The successful management requires correct identification of the cause. We report a case of VF storm in a patient with COVID 19 who responded to steroid therapy. Controlling the fulminant inflammation may reduce the burden of arrhythmia in appropriate cases.
ABSTRACT
Background: Patients (pts) with malignancies are at increased risk of morbidity and mortality from COVID-19. Among these pts, some of the higher case fatality ratios (CFR) reported are among pts with myeloid malignancies, ranging from 37 to 50% (Mehta V, Cancer Discov 2020;Ferrara F, Leukemia 2020). Levine Cancer Institute (LCI) has a robust hematologic malignancy and cellular therapy program that serves many pts with myeloid malignancies, seeing nearly 100 new diagnoses of acute myeloid leukemia per year. A strategy to mitigate risks associated with COVID-19 was established at LCI in partnership with Atrium Health's (AH) Hospital at Home (HAH). HAH was a system wide platform using telemedicine and home health services to assess and monitor COVID-19 + pts at high risk of complications. To augment HAH for our medically complex cancer pts, a virtual health navigation process involving expertise from across LCI, including a specialized nurse navigation team, was developed to rapidly identify LCI pts + for SARS-CoV-2, monitor them under physician supervision, and escalate care as needed with AH HAH. Along with the navigation platform, data-driven guidelines for detecting, monitoring, and managing LCI pts + for SARS-CoV-2 were swiftly employed across the extensive LCI network. Herein we report on the outcomes for LCI pts with myeloid malignancies + for SARS-CoV-2 and outline the employed risk mitigation strategies and their potential impact on these outcomes. Methods: An automated daily list of LCI pts + for SARS-CoV-2 was provided by AH Information Services. Each pt's chart was reviewed by a nurse navigator for hematologic or oncologic diagnosis, outpatient or inpatient status, and COVID-19 symptoms. Pts without a cancer diagnosis were not assigned a navigator. If hospitalized, a pt was not assigned a navigator;following discharge, if enrolled in HAH, a navigator was assigned. In collaboration with HAH, an algorithm for directing care was utilized (Figure 1). A diagnosis-specific navigator contacted and screened the pt with an assessment tool, which scored pts for surveillance and treatment needs (Table 1). Documentation was forwarded to the primary hematologist/oncologist. Comprehensive guidelines for testing, scheduling, management of + pts, research, and process changes were created, disseminated, and actively updated through LCI's EAPathways. For outcome analysis for pts with myeloid malignancies, pt vital status was updated through data cutoff (7/3/21). Results: From inception on 3/20/20 to 12/2/20, 974 LCI patients were identified as SARS-CoV-2 + and reviewed for nurse navigation. Of the 974 pts, including pts with benign and malignant diagnoses, 488 were navigated. Among all SARS-CoV-2 + LCI pts, 145 (15%) had a hematologic malignancy, including 37 (4%) pts with myeloid malignancies. Characteristics are shown in Table 2. Of the 37 pts, 18 (49%) were navigated. 70% with myeloid malignancies were on active treatment at the time of + test. Nearly 50% of those on active treatment were navigated. 46% were hospitalized with COVID-19, with this being the main reason for no assigned navigator. 24% of hospitalized pts were eventually assigned a navigator. Only 3 pts had undergone allogeneic stem cell transplantation (allo-SCT) with a median time from transplant to detection of SARS-CoV-2 of 9 months (range, 7-23). 2 out of 3 cases post allo-SCT were asymptomatic. No pt died from COVID-19 following allo-SCT. Among the navigated pts with myeloid malignancies, there was no death related to COVID-19. 4 pts, all of whom were hospitalized, died from COVID-19 (N=2, myelodysplastic syndrome with 1 on azacitidine;N=2, myeloproliferative neoplasm, both on hydrea). A CFR of 11% was demonstrated for LCI pts with myeloid malignancies. Conclusions: A multidisciplinary response strategy liaising between AH HAH and LCI followed, assessed, and assisted cancer pts + for SARS-CoV-2. With our embedded nurse navigation team's specialized attention along with enhanced physician oversight and close collaboration with AH HAH, opportunities f r care escalation or adjustments in cancer-focused care were promptly identified. In this setting, among the high-risk population of pts with myeloid malignancies, a lower CFR than has been reported was observed. A virtual navigation platform with HAH capabilities is a feasible, safe, and effective way to monitor and care for this high-risk population. [Formula presented] Disclosures: Moyo: Seattle Genetics: Consultancy. Chai: Cardinal Health: Membership on an entity's Board of Directors or advisory committees. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Grunwald: Amgen: Consultancy;Agios: Consultancy;Astellas: Consultancy;Daiichi Sankyo: Consultancy;Stemline: Consultancy;Bristol Myers Squibb: Consultancy;PRIME: Other;Trovagene: Consultancy;Blueprint Medicines: Consultancy;AbbVie: Consultancy;Med Learning Group: Other;Pfizer: Consultancy;Sierra Oncology: Consultancy;Janssen: Research Funding;Incyte: Consultancy, Research Funding;Gilead: Consultancy;MDEdge: Other;PER: Other;Cardinal Health: Consultancy;Karius: Consultancy. Copelan: Amgen: Consultancy.
ABSTRACT
Introduction: Pomalidomide is a third-generation immunomodulatory drug approved for relapsed and/or refractory Multiple Myeloma (RRMM). In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone demonstrated superior efficacy in patients with RRMM. PRIME study (CTRI/2019/10/021618) is testing this combination in Newly Diagnosed Multiple Myeloma (NDMM) Aim: To determine safety of Pomalidomide in combination with Bortezomib and dexamethasone (VPD) in NDMM Study design: A prospective, single arm, phase II study from a tertiary center. Both transplant eligible and ineligible patients with NDMM aged between 18-70 years are being recruited in the study. Patients with Plasma cell leukemia, POEMS and amyloidosis were excluded. The regimen consists of weekly Bortezomib 1.3mg/sq.m (subcutaneous), Tab. Pomalidomide 2-4mg once daily for 21days, and Tab Dexamethasone 20mg twice weekly, with the cycle repeating every 28 days, 9-12 cycles. Here we report the adverse events (AE) by NCI CTCAE v5.0, upon recruiting 26 patients, as predetermined in the study. Results: Of the proposed 45-50 patients, 26 patients were enrolled in the study between April 2020 to May 2021 and 23 (88.4%) have completed 4 cycles of VPD. The median age is 55years (18-70), and gender ratio 1:1. At disease presentation, bone lesions were the commonest (96.2%, n=25), IMWG high risk cytogenetics were seen in 42.4% (n=11), RISS-2 in 69.3% (n=18), IgG kappa paraproteinemia in 54% (n=14) patients and ECOG performance score 2-3 in 57.6%(n=15). Ten (38.5%) patients have completed 9 cycles, and 3 underwent auto-transplant (between Cycle 4 & 6). Protocol adherence was 96.1% (25/26 patients). Table-1 shows drug-induced toxicity, hematological toxicities were the commonest. Two patients withdrew consent in view of bortezomib-induced peripheral neuropathy. Serious adverse events (SAE) were reported in 9 (34.6%) patients and were considered unrelated to the regimen by the safety committee (PSVT=1, Bony pain=2, dyspnea=1, pneumonia=1, constipation=1, diarrhea=1, hypotension=1) and one death due to SARS-CoV2 pneumonia. Treatment delays of 2 weeks in 4 patients (SARS-CoV2 = 3, Syncope = 1) After 4 cycles (n=23), 6 (26%) patients were in stringent Complete Response (sCR), 17(74%) in Very Good partial response (VGPR) and 13 (56.5%) are Measurable Residual Disease (MRD) negative. Of 10 patients who completed cycle 9, 9 were MRD negative and 1 showed disease progression. Conclusion: Safety data from the PRIME study demonstrates that VPD regimen has a favorable tolerance profile in patients with NDMM. Early efficacy signals are encouraging, and recruitment continues. [Formula presented] Disclosures: Radhakrishnan: Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Emcure Pharmaceuticals: Research Funding;Intas Pharmaceuticals: Research Funding;Janssen India: Honoraria;NATCO Pharmaceuticals: Research Funding;Novartis India: Membership on an entity's Board of Directors or advisory committees;Roche India: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;AstraZeneca India: Honoraria, Speakers Bureau;Bristol-Myers-Squibb India: Membership on an entity's Board of Directors or advisory committees, Research Funding;Cipla Pharmaceuticals India: Research Funding;Aurigene: Speakers Bureau. Garg: Dr Reddys Laboratories: Honoraria, Speakers Bureau. Nair: Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Intas pharmaceuticals: Honoraria, Speakers Bureau;Mylan pharmaceuticals: Honoraria;Novartis India: Honoraria;Fresenius Kabi India: Honoraria;Cipla Pharmaceuticals: Honoraria, Speakers Bureau;Janssen India: Honoraria, Speakers Bureau. Chandy: Janssen: Honoraria;Pfizer: Honoraria;Intas Pharmaceuticals: Research Funding.