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1.
Cancer Cell ; 39(8): 1081-1090.e2, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1343145

ABSTRACT

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/immunology , Neoplasms/complications , Neoplasms/immunology , SARS-CoV-2/immunology , Seroconversion , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Female , Host-Pathogen Interactions/immunology , Humans , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/therapy , Public Health Surveillance , Risk Factors , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , Vaccination
2.
EPMA J ; 12(2): 155-176, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1300538

ABSTRACT

Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are: - Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects; - Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities.

3.
Nucleic Acids Res ; 49(W1): W174-W184, 2021 07 02.
Article in English | MEDLINE | ID: covidwho-1249328

ABSTRACT

Combinatorial therapies that target multiple pathways have shown great promises for treating complex diseases. DrugComb (https://drugcomb.org/) is a web-based portal for the deposition and analysis of drug combination screening datasets. Since its first release, DrugComb has received continuous updates on the coverage of data resources, as well as on the functionality of the web server to improve the analysis, visualization and interpretation of drug combination screens. Here, we report significant updates of DrugComb, including: (i) manual curation and harmonization of more comprehensive drug combination and monotherapy screening data, not only for cancers but also for other diseases such as malaria and COVID-19; (ii) enhanced algorithms for assessing the sensitivity and synergy of drug combinations; (iii) network modelling tools to visualize the mechanisms of action of drugs or drug combinations for a given cancer sample and (iv) state-of-the-art machine learning models to predict drug combination sensitivity and synergy. These improvements have been provided with more user-friendly graphical interface and faster database infrastructure, which make DrugComb the most comprehensive web-based resources for the study of drug sensitivities for multiple diseases.


Subject(s)
Algorithms , Databases, Factual , Drug Evaluation, Preclinical , Drug Therapy, Combination , Internet , COVID-19/drug therapy , Data Visualization , Datasets as Topic , Drug Synergism , Hemorrhagic Fever, Ebola/drug therapy , Humans , Machine Learning , Malaria/drug therapy , Neoplasms/drug therapy
4.
Front Immunol ; 12: 568959, 2021.
Article in English | MEDLINE | ID: covidwho-1247857

ABSTRACT

Molecular imaging using PET/CT or PET/MRI has evolved from an experimental imaging modality at its inception in 1972 to an integral component of diagnostic procedures in oncology, and, to lesser extent, in cardiology and neurology, by successfully offering in-vivo imaging and quantitation of key pathophysiological targets or molecular signatures, such as glucose metabolism in cancerous disease. Apart from metabolism probes, novel radiolabeled peptide and antibody PET tracers, including radiolabeled monoclonal antibodies (mAbs) have entered the clinical arena, providing the in-vivo capability to collect target-specific quantitative in-vivo data on cellular and molecular pathomechanisms on a whole-body scale, and eventually, extract imaging biomarkers possibly serving as prognostic indicators. The success of molecular imaging in mapping disease severity on a whole-body scale, and directing targeted therapies in oncology possibly could translate to the management of Coronavirus Disease 2019 (COVID-19), by identifying, localizing, and quantifying involvement of different immune mediated responses to the infection with SARS-COV2 during the course of acute infection and possible, chronic courses with long-term effects on specific organs. The authors summarize current knowledge for medical imaging in COVID-19 in general with a focus on molecular imaging technology and provide a perspective for immunologists interested in molecular imaging research using validated and immediately available molecular probes, as well as possible future targets, highlighting key targets for tailored treatment approaches as brought up by key opinion leaders.


Subject(s)
COVID-19/diagnosis , Molecular Imaging/methods , RNA, Viral/analysis , SARS-CoV-2/physiology , Animals , Diagnostic Tests, Routine , Humans , Magnetic Resonance Imaging , Positron-Emission Tomography , Predictive Value of Tests , Prognosis , Radioligand Assay
5.
BMC Cancer ; 21(1): 578, 2021 May 20.
Article in English | MEDLINE | ID: covidwho-1238711

ABSTRACT

BACKGROUND: The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. METHODS: ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. RESULTS: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. CONCLUSION: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Neoplasms/therapy , Aged , Ambulatory Care/statistics & numerical data , Belgium/epidemiology , COVID-19/complications , Cancer Care Facilities , Cohort Studies , Female , Health Personnel/statistics & numerical data , Humans , Male , Middle Aged , Neoplasms/epidemiology , Risk Factors , SARS-CoV-2
6.
Front Pharmacol ; 12: 612602, 2021.
Article in English | MEDLINE | ID: covidwho-1223895

ABSTRACT

To improve long-term outcomes of therapies for chronic diseases, health promotion and lifestyle modifications are the most promising and sustainable strategies. In addition, advances in digital technologies provide new opportunities to address limitations of drug-based treatments, such as medication non-adherence, adverse effects, toxicity, drug resistance, drug shortages, affordability, and accessibility. Pharmaceutical drugs and biologics can be combined with digital health technologies, including mobile medical apps (digital therapeutics), which offer additional clinical benefits and cost-effectiveness. Promises of drug+digital combination therapies are recognized by pharmaceutical and digital health companies, opening opportunities for integrating pharmacotherapies with non-pharmacological interventions (metapharmacology). Herein we present unique features of digital health technologies which can deliver personalized self-care modalities such as breathing exercises, mindfulness meditation, yoga, physical activity, adequate sleep, listening to preferred music, forgiveness and gratitude. Clinical studies reveal how aforementioned complimentary practices may support treatments of epilepsy, chronic pain, depression, cancer, and other chronic diseases. This article also describes how digital therapies delivering "medicinal" self-care and other non-pharmacological interventions can also be personalized by accounting for: 1) genetic risks for comorbidities, 2) adverse childhood experiences, 3) increased risks for viral infections such as seasonal influenza, or COVID-19, and 4) just-in-time stressful and traumatic circumstances. Development and implementation of personalized pharmacological-behavioral combination therapies (precision metapharmacology) require aligning priorities of key stakeholders including patients, research communities, healthcare industry, regulatory and funding agencies. In conclusion, digital technologies enable integration of pharmacotherapies with self-care, lifestyle interventions and patient empowerment, while concurrently advancing patient-centered care, integrative medicine and digital health ecosystems.

7.
Front Cardiovasc Med ; 8: 634291, 2021.
Article in English | MEDLINE | ID: covidwho-1221941

ABSTRACT

Anti-cancer treatment regimens can lead to both acute- and long-term myocardial injury due to off-target effects. Besides, cancer patients and survivors are severely immunocompromised due to the harsh effect of anti-cancer therapy targeting the bone marrow cells. Cancer patients and survivors can therefore be potentially extremely clinically vulnerable and at risk from infectious diseases. The recent global outbreak of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its infection called coronavirus disease 2019 (COVID-19) has rapidly become a worldwide health emergency, and on March 11, 2020, COVID-19 was declared a global pandemic by the World Health Organization (WHO). A high fatality rate has been reported in COVID-19 patients suffering from underlying cardiovascular diseases. This highlights the critical and crucial aspect of monitoring cancer patients and survivors for potential cardiovascular complications during this unprecedented health crisis involving the progressive worldwide spread of COVID-19. COVID-19 is primarily a respiratory disease; however, COVID-19 has shown cardiac injury symptoms similar to the cardiotoxicity associated with anti-cancer therapy, including arrhythmia, myocardial injury and infarction, and heart failure. Due to the significant prevalence of micro- and macro-emboli and damaged vessels, clinicians worldwide have begun to consider whether COVID-19 may in fact be as much a vascular disease as a respiratory disease. However, the underlying mechanisms and pathways facilitating the COVID-19-induced cardiac injury in cancer and non-cancer patients remain unclear. Investigations into whether COVID-19 cardiac injury and anti-cancer drug-induced cardiac injury in cancer patients and survivors might synergistically increase the cardiovascular complications and comorbidity risk through a "two-hit" model are needed. Identification of cardiac injury mechanisms and pathways associated with COVID-19 development overlapping with anti-cancer therapy could help clinicians to allow a more optimized prognosis and treatment of cancer survivors suffering from COVID-19. The following review will focus on summarizing the harmful cardiovascular risk of COVID-19 in cancer patients and survivors treated with an anti-cancer drug. This review will improve the knowledge of COVID-19 impact in the field of cardio-oncology and potentially improve the outcome of patients.

8.
Tumori ; 108(2): 177-181, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1197332

ABSTRACT

Lombardy has represented the Italian and European epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Although most clinical efforts within hospitals were diverted towards the care of virally infected patients, therapies for patients with cancer, including radiotherapy (RT), have continued. During both the first and second pandemic waves, several national and regional organizations provided Italian and Lombardian RT departments with detailed guidelines aimed at ensuring safe treatments during the pandemic. The spread of infection among patients and personnel was limited by adopting strict measures, including triage procedures, interpersonal distance, and adequate implementation of personal protective equipment (PPE). Screening procedures addressed to both the healthcare workforce and patients, such as periodic nasopharyngeal swabs, have allowed the early identification of asymptomatic or pauci-symptomatic COVID-19 cases, thus reducing the spread of the infection. Prevention of infection was deemed of paramount importance to protect both patients and personnel and to ensure the availability of a minimum number of staff members to maintain clinical activity. The choice of treating COVID-19-positive patients has represented a matter of debate, and the risk of oncologic progression has been weighted against the risk of infection of personnel and other patients. Such risk was minimized by creating dedicated paths, reserving time slots, applying intensified cleaning procedures, and supplying personnel and staff with appropriate PPE. Remote working of research staff, medical physicists, and, in some cases, radiation oncologists has prevented overcrowding of shared spaces, reducing infection spread.


Subject(s)
COVID-19 , Neoplasms , Radiation Oncology , COVID-19/epidemiology , Humans , Italy/epidemiology , Neoplasms/epidemiology , Neoplasms/radiotherapy , Pandemics/prevention & control , Personal Protective Equipment , SARS-CoV-2
9.
Eur J Breast Health ; 17(2): 188-196, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1191631

ABSTRACT

OBJECTIVE: In early 2020, the spread of coronavirus disease-2019 (COVID-19) led the World Health Organization to declare this disease a pandemic. Initial epidemiological data showed that patients with cancer were at high risk of developing severe forms of COVID-19. National scientific societies published recommendations modifying the patients' breast cancer (BC) management to preserve, in theory, quality oncologic care, avoiding the increased risk of contamination. The Senology International Society (SIS) decided to take an inventory of the actions taken worldwide. This study investigates COVID-19-related changes concerning BC management and analyzes the will to maintain them after the pandemic, evaluating their oncological safety consequences. MATERIALS AND METHODS: SIS network members participated in an online survey using a questionnaire (Microsoft® Forms) from June 15th to July 31st, 2020. RESULTS: Forty-five responses from 24 countries showed that screening programs had been suspended (68%); magnetic resonance imagines were postponed (73%); telemedicine was preferred when possible (71%). Surgeries were postponed: reconstructive (77%), for benign diseases (84%), and in patients with significant comorbidities (66%). Chemotherapy and radiotherapy protocols had been adapted in 28% of patients in both. Exception for telemedicine (34%), these changes in practice should not be continued. CONCLUSION: The SIS survey showed significant changes in BC's diagnosis and treatment during the first wave of the COVID-19 pandemic, but most of these changes should not be maintained. Indeed, women have fewer severe forms of COVID-19 and are less likely to die than men. The risk of dying from COVID-19 is more related to the presence of comorbidities and age than to BC. Stopping screening and delaying treatment leads to more advanced stages of BC. Only women aged over 65 with BC under treatment and comorbidities require adaptation of their cancer management.

10.
ESMO Open ; 6(3): 100123, 2021 06.
Article in English | MEDLINE | ID: covidwho-1171138

ABSTRACT

Inflammation is an established driver of severe SARS-CoV-2 infection and a mechanism linked to the increased susceptibility to fatal COVID-19 demonstrated by patients with cancer. As patients with cancer exhibit a higher level of inflammation compared with the general patient population, patients with cancer and COVID-19 may uniquely benefit from strategies targeted at overcoming the unrestrained pro-inflammatory response. Targeted and non-targeted anti-inflammatory therapies may prevent end-organ damage in SARS-CoV-2-infected patients with cancer and decrease mortality. Here, we review the clinical role of selective inhibition of pro-inflammatory interleukins, tyrosine kinase modulation, anti-tumor necrosis factor agents, and other non-targeted approaches including corticosteroids in their roles as disease-modulating agents in patients with COVID-19 and cancer. Investigation of these therapeutics in this highly vulnerable patient group is posited to facilitate the development of tailored therapeutics for this patient population, aiding the transition of systemic inflammation from a prognostic domain to a source of therapeutic targets.


Subject(s)
COVID-19 , Neoplasms , Anti-Inflammatory Agents , Humans , Inflammation , SARS-CoV-2
11.
Lancet Oncol ; 22(3): 309-320, 2021 03.
Article in English | MEDLINE | ID: covidwho-1164661

ABSTRACT

BACKGROUND: The indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England. METHODS: In this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis. FINDINGS: In 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances. INTERPRETATION: Radiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences. FUNDING: None.


Subject(s)
COVID-19/epidemiology , Neoplasms/radiotherapy , SARS-CoV-2 , Adult , Aged , Female , Humans , Male , Middle Aged , United Kingdom/epidemiology
12.
Viruses ; 13(3)2021 03 08.
Article in English | MEDLINE | ID: covidwho-1143612

ABSTRACT

The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes. Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies. We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48-72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy. Overall survival in those who received convalescent plasma was significantly higher than in the historical group (p = 0.03460). The plasma-treated group also showed a significantly milder course of infection (p = 0.03807), characterized by less severe symptoms and faster recovery (p = 0.00001). In conclusion, we have demonstrated that convalescent plasma is an effective treatment and its early administration leads to clinical improvement, increased viral clearance and longer overall survival in patients with hematological malignancies and COVID-19. To our knowledge, this is the first report to analyze the efficacy of convalescent plasma in a cohort of patients with hematological malignancies.


Subject(s)
COVID-19/therapy , Hematologic Neoplasms/mortality , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Cohort Studies , Female , Hematologic Neoplasms/therapy , Humans , Immunization, Passive , Male , Middle Aged , Plasma/immunology , Survival , Treatment Outcome , Young Adult
13.
ACS Omega ; 5(50): 32724-32737, 2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-1120896

ABSTRACT

The σ1 receptor is implicated in regulating a diverse range of physiology and is a target for developing therapies for cancer, pain management, neural degradation, and COVID-19. This report describes 36 phenethylamine-containing 3-amino-chromane ligands, which bind to σ1 with low nM affinities. The family consists of 18 distinct compounds and each enantiomer was independently assayed. Three compounds with the greatest affinity bind in the 2 nM K i range (∼8.7 pK i). Furthermore, ligands with the (3R,4R) absolute stereochemistry on the 3-amino-chromane core have a higher affinity and greater σ1 versus TMEM97 selectivity. The most promising ligands were assayed in 661W cells, which did not show significant protective effects.

14.
Int J Mol Sci ; 22(5)2021 Feb 28.
Article in English | MEDLINE | ID: covidwho-1120888

ABSTRACT

Immunotherapy is a highly emerging form of breast cancer therapy that enables clinicians to target cancers with specific receptor expression profiles. Two popular immunotherapeutic approaches involve chimeric antigen receptor-T cells (CAR-T) and bispecific antibodies (BsAb). Briefly mentioned in this review as well is the mRNA vaccine technology recently popularized by the COVID-19 vaccine. These forms of immunotherapy can highly select for the tumor target of interest to generate specific tumor lysis. Along with improvements in CAR-T, bispecific antibody engineering, and therapeutic administration, much research has been done on novel molecular targets that can especially be useful for triple-negative breast cancer (TNBC) immunotherapy. Combining emerging immunotherapeutics with tumor marker discovery sets the stage for highly targeted immunotherapy to be the future of cancer treatments. This review highlights the principles of CAR-T and BsAb therapy, improvements in CAR and BsAb engineering, and recently identified human breast cancer markers in the context of in vitro or in vivo CAR-T or BsAb treatment.


Subject(s)
Breast Neoplasms/therapy , Immunotherapy/methods , Animals , Antibodies, Bispecific/immunology , Antibodies, Bispecific/therapeutic use , Biomarkers, Tumor , Breast Neoplasms/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Cancer Vaccines/administration & dosage , Cancer Vaccines/immunology , Female , Humans , Immunotherapy, Adoptive/methods , Molecular Targeted Therapy , Receptors, Chimeric Antigen/immunology , SARS-CoV-2/immunology , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/therapy , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology
15.
Radiol Oncol ; 55(2): 121-129, 2021 03 05.
Article in English | MEDLINE | ID: covidwho-1119525

ABSTRACT

BACKGROUND: COVID-19 infection is particularly aggressive in frail patients, as cancer patients. Therefore, the more suitable management of the oncological patient requires a multidisciplinary assessment, to identify which patients should be treated, as inpatients or outpatients, and which treatments can be procrastinated. CONCLUSIONS: The role of radiologist is crucial, and, all cancer patients who need an imaging evaluation will need to be studied, using the most appropriate imaging tools related to the clinical question and paying a special attention to preserve public health. Guidelines are necessary in the correct organization of a radiology unit to manage patients with suspected or confirmed COVID-19 infection, and whenever possible, a satellite radiography center with dedicated equipment should be used to decrease the transmission risk.


Subject(s)
COVID-19/complications , COVID-19/diagnosis , Clinical Protocols , Neoplasms/complications , Neoplasms/diagnosis , Radiology Department, Hospital/organization & administration , COVID-19/therapy , COVID-19/transmission , COVID-19 Testing , Cross Infection/prevention & control , Humans , Incidental Findings , Neoplasms/therapy , Patient Care Team/organization & administration , Patient Isolation , Personal Protective Equipment , SARS-CoV-2 , Triage
16.
J Hematol Oncol ; 14(1): 38, 2021 02 27.
Article in English | MEDLINE | ID: covidwho-1105724

ABSTRACT

Less than a year since the start of the COVID-19 pandemic, ten vaccines against SARS-CoV-2 have been approved for at least limited use, with over sixty others in clinical trials. This swift achievement has generated excitement and arrives at a time of great need, as the number of COVID-19 cases worldwide continues to rapidly increase. Two vaccines are currently approved for full use, both built on mRNA and lipid nanotechnology platforms, a success story of mRNA technology 20 years in the making. For patients with cancer, questions arise around the safety and efficacy of these vaccines in the setting of immune alterations engendered by their malignancy and/or therapies. We summarize the current data on leading COVID-19 vaccine candidates and vaccination of patients undergoing immunomodulatory cancer treatments. Most current cancer therapeutics should not prevent the generation of protective immunity. We call for more research in this area and recommend that the majority of patients with cancer receive COVID vaccinations when possible.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/complications , COVID-19/prevention & control , Neoplasms/complications , Animals , Antineoplastic Agents/therapeutic use , COVID-19/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Humans , Immunotherapy , Neoplasms/immunology , Neoplasms/therapy , Pandemics/prevention & control
17.
Dig Surg ; 38(2): 158-165, 2021.
Article in English | MEDLINE | ID: covidwho-1105564

ABSTRACT

BACKGROUND: This survey aimed to register changes determined by the COVID-19 pandemic on pancreatic surgery in a specific geographic area (Germany, Austria, and Switzerland) to evaluate the impact of the pandemic and obtain interesting cues for the future. METHODS: An online survey was designed using Google Forms focusing on the local impact of the pandemic on pancreatic surgery. The survey was conducted at 2 different time points, during and after the lockdown. RESULTS: Twenty-five respondents (25/56) completed the survey. Many aspects of oncological care have been affected with restrictions and delays: staging, tumor board, treatment selection, postoperative course, adjuvant treatments, outpatient care, and follow-up. Overall, 60% of respondents have prioritized pancreatic cancer patients according to stage, age, and comorbidities, and 40% opted not to operate high-risk patients. However, for 96% of participants, the standards of care were guaranteed. DISCUSSION/CONCLUSIONS: The first wave of the COVID-19 pandemic had an important impact on pancreatic cancer surgery in central Europe. Guidelines for prompt interventions and prevention of the spread of viral infections in the surgical environment are needed to avoid a deterioration of care in cancer patients in the event of a second wave or a new pandemic. High-volume centers for pancreatic surgery should be preferred and their activity maintained. Virtual conferences have proven to be efficient during this pandemic and should be implemented in the near future.


Subject(s)
COVID-19/prevention & control , Health Services Accessibility/trends , Pancreatectomy/trends , Pancreatic Neoplasms/surgery , Practice Patterns, Physicians'/trends , Aftercare/methods , Aftercare/standards , Aftercare/trends , Attitude of Health Personnel , COVID-19/epidemiology , Europe/epidemiology , Health Care Surveys , Health Services Accessibility/standards , Humans , Infection Control/methods , Infection Control/trends , Neoplasm Staging , Pancreatectomy/standards , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Pandemics , Patient Acceptance of Health Care , Perioperative Care/methods , Perioperative Care/standards , Perioperative Care/trends , Practice Guidelines as Topic , Practice Patterns, Physicians'/standards , Time-to-Treatment/standards , Time-to-Treatment/trends
18.
J Microbiol ; 59(2): 124-131, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1060272

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused corona virus disease 2019 (COVID-19) pandemic and led to mass casualty. Even though much effort has been put into development of vaccine and treatment methods to combat COVID-19, no safe and efficient cure has been discovered. Drug repurposing or drug repositioning which is a process of investigating pre-existing drug candidates for novel applications outside their original medical indication can speed up the drug development process. Raloxifene is a selective estrogen receptor modulator (SERM) that has been approved by FDA in 1997 for treatment and prevention of postmenopausal osteoporosis and cancer. Recently, raloxifene demonstrates efficacy in treating viral infections by Ebola, influenza A, and hepatitis C viruses and shows potential for drug repurposing for the treatment of SARS-CoV-2 infection. This review will provide an overview of raloxifene's mechanism of action as a SERM and present proposed mechanisms of action in treatment of viral infections.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Repositioning , Raloxifene Hydrochloride/therapeutic use , SARS-CoV-2/drug effects , Estrogen Antagonists/therapeutic use , Estrogens/agonists , Humans , Molecular Docking Simulation , Osteoporosis, Postmenopausal/drug therapy , Selective Estrogen Receptor Modulators/therapeutic use
19.
Aging Cell ; 20(2): e13316, 2021 02.
Article in English | MEDLINE | ID: covidwho-1057943

ABSTRACT

The ageing of the global population brings about unprecedented challenges. Chronic age-related diseases in an increasing number of people represent an enormous burden for health and social care. The immune system deteriorates during ageing and contributes to many of these age-associated diseases due to its pivotal role in pathogen clearance, tissue homeostasis and maintenance. Moreover, in order to develop treatments for COVID-19, we urgently need to acquire more knowledge about the aged immune system, as older adults are disproportionally and more severely affected. Changes with age lead to impaired responses to infections, malignancies and vaccination, and are accompanied by chronic, low-degree inflammation, which together is termed immunosenescence. However, the molecular and cellular mechanisms that underlie immunosenescence, termed immune cell senescence, are mostly unknown. Cellular senescence, characterised by an irreversible cell cycle arrest, is thought to be the cause of tissue and organismal ageing. Thus, better understanding of cellular senescence in immune populations at single-cell level may provide us with insight into how immune cell senescence develops over the life time of an individual. In this review, we will briefly introduce the phenotypic characterisation of aged innate and adaptive immune cells, which also contributes to overall immunosenescence, including subsets and function. Next, we will focus on the different hallmarks of cellular senescence and cellular ageing, and the detection techniques most suitable for immune cells. Applying these techniques will deepen our understanding of immune cell senescence and to discover potential druggable pathways, which can be modulated to reverse immune ageing.


Subject(s)
Cellular Senescence , Immunosenescence , Leukocytes/physiology , Animals , Biomarkers/metabolism , Humans , Oxidative Stress , Proteostasis
20.
Br Med Bull ; 137(1): 13-27, 2021 03 25.
Article in English | MEDLINE | ID: covidwho-1054267

ABSTRACT

BACKGROUND: Many drugs approved for other indications can control the growth of tumor cells and limit adverse events (AE). DATA SOURCES: Literature searches with keywords 'repurposing and cancer' books, websites: https://clinicaltrials.gov/, for drug structures: https://pubchem.ncbi.nlm.nih.gov/. AREAS OF AGREEMENT: Introducing approved drugs, such as those developed to treat diabetes (Metformin) or inflammation (Thalidomide), identified to have cytostatic activity, can enhance chemotherapy or even replace more cytotoxic drugs. Also, anti-inflammatory compounds, cytokines and inhibitors of proteolysis can be used to control the side effects of chemo- and immuno-therapies or as second-line treatments for tumors resistant to kinase inhibitors (KI). Drugs specifically developed for cancer therapy, such as interferons (IFN), the tyrosine KI abivertinib TKI (tyrosine kinase inhibitor) and interleukin-6 (IL-6) receptor inhibitors, may help control symptoms of Covid-19. AREAS OF CONTROVERSY: Better knowledge of mechanisms of drug activities is essential for repurposing. Chemotherapies induce ER stress and enhance mutation rates and chromosome alterations, leading to resistance that cannot always be related to mutations in the target gene. Metformin, thalidomide and cytokines (IFN, tumor necrosis factor (TNF), interleukin-2 (IL-2) and others) have pleiomorphic activities, some of which can enhance tumorigenesis. The small and fragile patient pools available for clinical trials can cloud the data on the usefulness of cotreatments. GROWING POINTS: Better understanding of drug metabolism and mechanisms should aid in repurposing drugs for primary, adjuvant and adjunct treatments. AREAS TIMELY FOR DEVELOPING RESEARCH: Optimizing drug combinations, reducing cytotoxicity of chemotherapeutics and controlling associated inflammation.


Subject(s)
COVID-19/drug therapy , Drug Repositioning , Neoplasms/drug therapy , Humans
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