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1.
BMJ Open ; 12(12):e067251, 2022.
Article in English | MEDLINE | ID: covidwho-2193801

ABSTRACT

INTRODUCTION: Sepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant hyperinflammation or macrophage activation-like syndrome (MALS), and on the other side patients whose immune response is characterised by immunoparalysis. A sizeable group of patients are situated between the two extremes. Recognising immune endotype is very important in order to choose the appropriate immunotherapeutic approach for each patient resulting in the best chance to improve the outcome.

2.
Science ; 370(6522):1286, 2020.
Article in English | EMBASE | ID: covidwho-2193388
3.
Journal of Cellular and Molecular Medicine (Online) ; 27(2):222-231, 2023.
Article in English | ProQuest Central | ID: covidwho-2192724

ABSTRACT

Incidence of Malignant Melanoma has become the 5th in the UK. To date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology-based strategies. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. In the present in vitro study, the antitumour effect of cord blood stem cell (CBSC)-derived exosomes was confirmed by the CCK-8 assay (p < 0.05) on CHL-1 melanoma cells and improve the repair mechanism on lymphocytes from melanoma patients. Importantly, no significant effect was observed in healthy lymphocytes when treated with the exosome concentrations at 24, 48 and 72 h. Comet assay results (OTM and %Tail DNA) demonstrated that the optimal exosome concentration showed a significant impact (p < 0.05) in lymphocytes from melanoma patients whilst causing no significant DNA damage in lymphocytes of healthy volunteers was 300 μg/ml. Similarly, the Comet assay results depicted significant DNA damage in a melanoma cell line (CHL-1 cells) treated with CBSC-derived exosomes, both the cytotoxicity of CHL-1 cells treated with CBSC-derived exosomes exhibited a significant time-dependent decrease in cell survival. Sequencing analysis of CBSC exosomes showed the presence of the let-7 family of miRNAs, including let-7a-5p, let-7b-5p, let-7c-5p, let-7d-3p, let-7d-5p and two novel miRNAs. The potency of CBSC exosomes in inhibiting cancer progression in lymphocytes from melanoma patients and CHL-1 cells whilst causing no harm to the healthy lymphocytes makes it a potential candidate as an anticancer therapy.

4.
Open Forum Infectious Diseases ; 9(Supplement 2):S761, 2022.
Article in English | EMBASE | ID: covidwho-2189937

ABSTRACT

Background. Determining if a patient with SARS-CoV-2 remains infectious is an infection control challenge in healthcare settings;specially, among critically ill or profoundly immunosuppressed patients. We use an assay that detects minus-strand RNA as a surrogate for actively replicating SARS-CoV-2. We report positive strand-specific assays in relationship to time since admission and describe patients with a detectable strand-specific assay >20 days since admission. Methods. We use a 2-step rRT-PCR specific to the minus strand of the SARS-CoV-2 envelope gene. The strand-specific assay is used to evaluate for infectivity in asymptomatic patients with a positive admission screening or pre-procedural test or if ongoing replication is suspected (critical illness or profound immunosuppression). We retrieved strand-specific test results for patients hospitalized at Stanford Healthcare during August 2020-March 2022. We describe clinical characteristics for patients with a detectable minus strand-specific test >20 days since admission. Results. A total of 774 strand-specific tests were collected from 624 hospitalized patients. A total of 523 patients had only one test (84%) and 101 (16%) had >=2 tests. The test positivity rate varied by time since admission: 19% in tests performed 0-5 days, 28% in 6-10 days, 22% in 11-20 days, and 41% in those >20 days since admission. Among 35 patients tested >20 days since admission, 13 (37%) had >=1 detectable minus strand-specific test. Most were male (n=8, 62%) and mean age was 59. Of 13 patients with a detectable assay, seven (54%) had prolonged viral replication with persistent symptoms and detectable minus strand assays for >20 days from symptom onset. Of these seven patients, four had a transplant (3 lung, 1 liver), 1 ovarian cancer, 1 CAR-T cell therapy, and 1 ESRD without immunosuppression. The remaining eight patients with a detectable assay >20 days since admission had illness onset while hospitalized. Conclusion. Among hospitalized patients with SARS-CoV-2 infection, we found a varying positivity rate according to the timing of testing, possibly reflecting different indications for the test. The strand-specific assay may help assess for infectiousness in profoundly immunocompromised patients.

5.
Nature Cancer ; 3(12):1405, 2022.
Article in English | EMBASE | ID: covidwho-2186112
6.
Nature Cancer ; 3(12):1432-1433, 2022.
Article in English | EMBASE | ID: covidwho-2186109
7.
Nature Medicine ; 28(12):2441-2443, 2022.
Article in English | ProQuest Central | ID: covidwho-2185959

ABSTRACT

Up-and-coming researchers who are blazing a trail in their respective fields share what they are most excited about and where their research going in the next 5 years.

8.
Medicine (United Kingdom) ; 51(1):80-85, 2023.
Article in English | EMBASE | ID: covidwho-2181717

ABSTRACT

The incidence of cancer continues to rise, with an estimated 1 in 2 of the UK population born after 1960 diagnosed with malignancy at some point during their lifetime. This is in the context of an ageing population with increasing multimorbidity and polypharmacy. Cancer patients are frequent users of emergency care services and have a high rate of ambulance conveyance and hospital admission after review in emergency departments. Presentations can be a consequence of the cancer, its treatment or coexistent morbidity. Given the expanding armamentarium of cancer therapies, acute and general physicians are faced with a myriad of complex issues and require a knowledge of the broad principles of initial assessment, initial management and timely access to the wider multi-professional cancer team. Copyright © 2022

9.
Journal of the Neurological Sciences ; 444 (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-2180813
10.
Cell Reports Methods ; : 100388, 2023.
Article in English | ScienceDirect | ID: covidwho-2177944

ABSTRACT

Summary CD4+ T cells are critical to the immune system and perform multiple functions;therefore, their identification and characterization are crucial to better understanding the immune system in both health and disease states. However, current methods rarely preserve their ex vivo phenotype, thus limiting our understanding of their in vivo functions. Here we introduce a flexible, rapid, and robust platform for ex vivo CD4+ T cell identification. By combining MHCII allele purification, allele-independent peptide loading, and multiplexed flow cytometry technologies, we can enable high-throughput personalized CD4+ T cell identification, immunophenotyping, and sorting. Using this platform in combination with single-cell sorting and multimodal analyses, we identified and characterized antigen-specific CD4+ T cells relevant to COVID-19 and cancer neoantigen immunotherapy. Overall, our platform can be used to detect and characterize CD4+ T cells across multiple diseases, with potential to guide CD4+ T cell epitope design for any disease-specific immunization strategy.

11.
European Geriatric Medicine ; 13(Supplement 1):S405-S406, 2022.
Article in English | EMBASE | ID: covidwho-2175456

ABSTRACT

Background: Biologic and immunosuppressive therapies play important roles in the management of a wide variety of dermatologic diseases. However, immunotherapies can negatively affect normal immune functioning, placing these patients at risk of infection [1]. The strength of the immune system also declines with increasing age. Vaccinations reduce the risk of susceptibility to infections. Thus, it is recommended that vaccinations against influenza, pneumococcal and COVID-19 infections are given to boost patient's defence while on immunosuppressant medications [2]. In addition, people over 65 years are at the highest risk of serious illness from COVID-19 if they have not been vaccinated [3]. Therefore, in accordance with the British Association of Dermatology guidelines (August 2021), patients on biologic therapies can and should have their COVID-19, influenza and pneumococcal vaccinations [2, 4]. MethodologyWe conducted a retrospective audit of all patients over the age of 65 years on biological therapies in the dermatology clinic between March 2021 and March 2022. Data on patients COVID-19, influenza and pneumococcal vaccination status were obtained from the departmental dermatology database (Filemaker Pro) and patients' medical records. In patients where the vaccine status wasn't documented in their medical records these patients were telephoned about their vaccine status. Findings were compared with the British association guidelines [2, 4], which were our audit standard. The data was subsequently analysed using Microsoft Excel. ResultsEighteen patients over the age of 65 years, were on biological therapies in the Dermatology Department, between March 2021 and March 2022. 44% (n = 8) of patients were between 65 and 70 years old, 28% (n = 5) were between 70 to 75 years old and 28% (n = 5) were above 75 years. The mean age was 71 years (+/- sd 5.2). The gender distribution was equal: 50% (n = 9) male, 50% (n = 9) female. Biologic therapies were indicated for treatment of psoriasis in 94% (n = 17) of patients and for treatment of eczema in one patient (6%). With regard to biological therapies, 17% (n = 3) of patients were treated with adalimumab, 16% (n = 3) were receiving Etanercept, 28% (n = 5) were receiving secukinumab, 11% (n = 2) were receiving ixekizumab, 11% (n = 2) were receiving guselkumab, 5% (n = 1) were receiving ustekinumab, 5% (n = 1) were receiving dupilumab and 5% (n = 1) were receiving risankizumab. All patients (100%, n = 18) had received all three of their COVID-19 vaccines. 50% (n = 8) were awaiting their 4th covid vaccination. 94% (n = 17) of patients had received their influenza vaccine in 2021. 66% (n = 12) of patients had received their pneumococcal vaccination in the last 5 years. We advised the patients who had not received their recommended vaccinations to receive it. Conclusion(s): This audit confirms dermatology patients over the age of sixty-five years, demonstrate excellent compliance receiving their covid-19 vaccinations, as recommended by the BAD2,4. This is important as patients over 65 years who are unvaccinated are recognised as being at the highest risk of serious infection from COVID-19. However, only 66% of patients had received their pneumococcal vaccination in the previous 5 years in contrast with 94% who had received their influenza vaccine in 2021, illustrating the need for educational intervention on the importance of all three vaccinations in this high risk patient group. We plan to perform a reaudit next year to assess compliance with vaccinations following patient education in order to complete the audit cycle.

12.
Neurological Sciences ; 43(Supplement 1):S488, 2022.
Article in English | EMBASE | ID: covidwho-2174340

ABSTRACT

Introduction: Since the beginning of the Sars-Cov-2 pandemic, several evidences have been gathered on the use of Disease Modifying Drugs (DMTs) in patients with Multiple Sclerosis (MS) [1]. As is well known, the pandemic has changed the management ofMS as well as changed the previously applied therapeutic choice paradigms [2]. The introduction of the Sars-Cov-2 vaccine marked a turning point for MS patients, considered among "fragile patients" [3]. Aim(s): The objective of this study is to describe changes about the use of first-line DMTs in patients with a new diagnosis ofMS, comparing the semester before and after the start of vaccination campaign for Sars-Cov- 2. Method(s): The study included patients newly diagnosed with MS according to McDonald's 2017 criteria. The proportion of patients initiated into the use of Interferon Beta (IFN), Dimethylfumarate (DMF) and Teriflunamide (TERI) was defined as a proportion for the previous semester (October 2020- March 2021) and subsequent (April 2021 - September 2021) to the avaibility of Sars-Cov-2 vaccine. The determinants of the choice of first-line DMTs were evaluated through regression analysis. Result(s): The study included 134 patients, including 40 (29.9%) male, average age of 38.3 +/- 12.3 years, disease duration of 3.0 +/- 4.6 years, average EDSS of 1.7 +/- 1.1. Among these, 75 (56%) patients started a first-line DMTs in the semester before the start of vaccination campaign [IFN 13 (9.7%), TERI 6 (4.5%), GA 28 (20.9%), DMF 28 (20.9%)], while 59 (44%) in the following semester [IFN 4 (3%), TERI 11(8.2%), GA 12 (8.9%) and DMF 32 (23.9%)]. A reduction of 40% and 53% respectively in the use of GA and IFN was observed in the semester following the start of the vaccination campaign. In contrast, an increase of 29 % in the use of TERI and 6% in the use of DMF respectively was reported in the semester following the start of the vaccination campaign. The regression analysis shows the use of injection therapies (IFN and GA) being associated with female gender (p= 0.032) and with the previous semester to the availability of Sars-Cov-2 vaccine (p=0.006). In contrast, the use of TERI is associated with male gender (p=0.031) and with the following semester the introduction of the vaccine (p=0.05). About the use of DMF, a relationship with the post-introduction semester of the vaccine has been observed (p=0.037);beyond this, the relapse rate in the previous 2 years is the strongest determinant in the choice of this treatment (p=0.001). Conclusion(s):Our data show howthe start of the vaccination campaign for Sars-Cov-2 influenced the use of first-line immunotherapies in patients with new diagnosis of MS.

13.
Neurological Sciences ; 43(Supplement 1):S376, 2022.
Article in English | EMBASE | ID: covidwho-2174310

ABSTRACT

Objectives: Longitudinal studies of SARS-CoV-2 vaccine-induced immune responses in patients with autoimmune neurological conditions (ANC) requiring immunotherapy are needed to optimize clinical care. Therefore, our aim was to report data on the longitudinal durability of two dose mRNA vaccination and the T cell response in ANC patients. Additionally, humoral and T cell responses were assessed in a subgroup of patients who received a third dose of mRNA-1273 or BNT162b2. Material: The ANCOVAX is a longitudinal study including ANC patients vaccinated with two doses of BNT162b2 or mRNA-1273 between March and August 2021[1]. Serum samples were collected 1 (T1), 3 (T3), 6 (T6) months after the second dose. PBMCs were collected in a subset of patients at T6. Method(s): IgG antibodies to the spike receptor binding domain protein (anti- RBD IgG) were measured using the Elecsys anti-SARS-CoV-2 ECLIA assay (Roche). SARS-CoV-2-specific T cell immunity was determined using a T-SPOT Discovery SARS-CoV-2 kit (Oxford Immunotec). Result(s): 294 patients were included in the follow-up study. Before T6, 86 patients received a booster dose. One month after the two-dose primary vaccination (T1), 265 patients (91%) had anti-RBD IgG antibodies, whereas 29 (9%) were seronegative. The highest nonresponder rate was associated with anti-CD20 therapy and BNT126b vaccine (p<0.0001). Antibody titers progressively declined three (p<0.0001) and six months (p<0.0001) after vaccination in the nonbooster group. However, most patients receiving immune therapies including steroids, AZA, IVIG and DMTs remained seropositive at 6 months;those who became seronegative were mainly in the anti-CD20 group. In the booster group, antibody levels significantly increased, with an overall seropositivity rate of 95.2%. Three previously seronegative patients, all on anti-CD20 therapy, remained seronegative. The T cell response was assessed in 57 patients. A logistic regression model showed that, independently from the booster dose, a positive T cell response was associated with anti-CD20 therapy. The T cell response did not correlate with antibody levels at T6. Discussion(s): Antibody levels declined over time in ANC patients. However, only in patients treated with anti-CD20 therapy antibody levels declined below the threshold of detection within six months after the second dose. However, despite a blunted humoral response, the T cell response was increased in patients receiving anti-CD20 therapy. In addition, the booster dose, significantly increased antibody levels. Conclusion(s): Our study shows variation in antibody responses across ANC patients receiving different immunotherapies and supports the need of immunomonitoring and individualized vaccination schedules in ANC patients.

14.
Cancer ; 129(2):170, 2023.
Article in English | MEDLINE | ID: covidwho-2172768
15.
Cancer (0008543X) ; 129(2):168-169, 2023.
Article in English | Academic Search Complete | ID: covidwho-2172767

ABSTRACT

This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, Alex A. Adjei, MD, PhD, believes that oncology is at the frontier of medicine and that significant scientific advances in cancer therapies over the years are history‐making events. In addition, recent studies show that men with prostate cancer have significantly different gut microbiota than men who do not have prostate cancer, and that messenger RNA COVID‐19 vaccines are safe for people with cancer undergoing immunotherapy. [ FROM AUTHOR]

16.
Annals of Gastroenterological Surgery ; 7(1):7-9, 2023.
Article in English | ProQuest Central | ID: covidwho-2172353

ABSTRACT

Furthermore, for ESCC conversion therapy with curative intent would be provided by surgical resection or definitive chemoradiotherapy. [...]the concept of conversion therapy needs to be discussed specifically for ESCC. Furthermore, unlike gastric cancer, the surgical treatment for ESCC occasionally requires three-field lymphadenectomy, and the incidence of postoperative complications is relatively high. [...]transthoracic esophagectomy accompanied by metastatectomy would be highly invasive. DISCLOSURE Conflict of Interest: Yuko Kitagawa reports grants and personal fees from Asahi Kasei Pharma Co., grants, personal fees, and other from Ono Pharmaceutical Co., Ltd., grants and personal fees from Otsuka Pharmaceutical Factory, Inc., grants and personal fees from Nippon Covidien Inc., grants, personal fees, and other from Taiho Pharmaceutical Co., Ltd, grants, personal fees, and other from Chugai Pharmaceutical Co., Ltd., grants, and personal fees from Kaken Pharmaceutical Co., Ltd., personal fees from AstraZeneca K.K., personal fees from Ethicon, Inc., personal fees from Olympus Co., personal fees from Shionogi & Co., Ltd., personal fees and other from Bristol-Myers Squibb K.K., personal fees from MSD K.K., personal fees from Smith & Nephew KK, personal fees from Aska Pharmaceutical Co., Ltd., personal fees from Miyarisan Pharmaceutical Co. Ltd., personal fees from Toray Industries, Inc., personal fees from Daiichi Sankyo Company, Ltd., personal fees from Chugai Foundation for Innovative Drug Discovery Science, personal fees from Nippon Kayaku Co., Ltd., grants from Yakult Honsha Co. Ltd., grants from Otsuka Pharmaceutical Co., Ltd., grants from Tsumura & Co., grants from Sumitomo Pharma Co., Ltd., grants from EA Pharma Co., Ltd., grants from Eisai Co., Ltd., grants from Kyowa Kirin Co., Ltd., grants from Medicon Inc., grants from Takeda Pharmaceutical Co., Ltd., grants from Teijin Pharma Ltd., outside the submitted work;Ken Kato reports research grants from MSD;Ono Pharmaceutical Co.;Merck Serono;Bayer;Beigene;Oncologys Biopharma;Chugai Pharmaceutical Co.;and Shionogi.

17.
Open Forum Infectious Diseases. Conference: Infectious Diseases Week, IDWeek ; 9(Supplement 2), 2022.
Article in English | EMBASE | ID: covidwho-2167500

ABSTRACT

The proceedings contain 1886 papers. The topics discussed include: clinical features and burden of post-acute sequelae of SARS-CoV-2 infection in children and adolescents;demonstration of stable clusters of symptoms in long covid;longitudinal analysis of t cells in COVID-19 survivors with post-acute sequelae of COVID-19 reveals associations between individual symptoms and inflammatory indexes;long-term health outcomes of individuals who are infected with SARS-CoV-2 and develop COVID-19;SARS-CoV-2 infection is associated with decreased reported physical fitness in a us military longitudinal cohort;impact of early post-transplant multidrug-resistant organism detection among renal transplant recipients, 2005-2021;incidence rates of invasive aspergillosis among lung transplant recipients in timeperiods with universal and targeted antifungal prophylaxis - a nationwide cohort study;infectious outcomes of car t-cell therapy: longitudinal follow up and risk stratification;and one-month humoral response following two doses of COVID-19 vaccines in specific populations - anrs0001s COV POPART cohort study.

18.
Medical Journal of Dr DY Patil Vidyapeeth ; 15(8):210-214, 2022.
Article in English | Scopus | ID: covidwho-2202068

ABSTRACT

Objective: The objective of this study is to delineate the characteristics and outcome of Pediatric Inflammatory Multisystem Syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection (PIMS-TS) in Eastern Indian settings. Materials and Methods: We conducted a prospective observational multicentric study from May 2020 to August 2020, collecting data on clinical profile, investigation findings, and outcome of the children aged 1 month-12 years admitted with the features of coronavirus disease 2019 (COVID-19) related hyperinflammation satisfying criteria for PIMS-TS from three tertiary care hospitals of Kolkata. Results: A total of 38 patients fulfilling the criteria of PIMS-TS were recruited. The median age of the study population was 5 years (1.9-8 years). Gastrointestinal symptoms were present in 33 (86.6%) of patients. Nasopharyngeal swab for COVID-19 reverse transcriptase-polymerase chain reaction was positive in 19 (50%) of patients, and immunoglobulin G antibody against COVID-19 was found in 12 (66.6%) of patients, whereas 19 (50%) of patients had a positive contact history of SARS-Co-V2 exposure. The features of Kawasaki, like illness with coronary changes, were seen in 12 (32%) cases, whereas myocarditis with ejection fraction <55% was reported in 17 (45%) of patients. Intensive care admissions were needed in 27 (71%) patients, and inotropes were given in 18 (47%), whereas four patients required mechanical ventilator support. Immunotherapy was used in 32 (84%) of patients. The outcome was good, with one death. Conclusions: PIMS TS has varied clinical presentation ranging from milder cases to severe cardiac dysfunction with shock. However, timely intervention and prompt initiation of immunomodulators can improve the prognosis. © 2022 by the Author(s).

19.
Journal of Neurocritical Care ; 15(2):131-135, 2022.
Article in English | Scopus | ID: covidwho-2204647

ABSTRACT

Background: Acute disseminated encephalomyelitis (ADEM)-like white matter disease, a rare complication of coronavirus disease 2019 (COVID-19), is a potentially life-threatening neurological disorder. The objective of this study was to report the successful treatment of post–COVID-19 ADEM with urgent immunotherapy and neurointensive management. Case Report: A 53-year-old female patient was referred to our hospital with a 2-day history of progressive mental deterioration and was diagnosed with ADEM after COVID-19. The patient's symptoms worsened despite the administration of high-dose steroids, and targeted temperature management was employed to manage brain edema. Additionally, the neurointensivist decided to use intravenous immunoglobulin early for intractable post–COVID-19 ADEM. Her mental status and neuroimaging findings showed rapid im-provement at about 3 months after admission. Conclusion: This case highlights that if the patient's symptoms worsen despite high-dose steroid administration in the acute stage, early use of intravenous immunoglobulin is expected to have a positive effect on the prognosis of patients with post–COVID-19 ADEM. © 2022 The Korean Neurocritical Care Society.

20.
Oncology in Clinical Practice ; 18(6):406-409, 2022.
Article in English | Scopus | ID: covidwho-2202818

ABSTRACT

The use of pembrolizumab with chemotherapy in first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) is an opportunity for patients to suppress their disease and increase their chances of life extension. COVID-19 (Coronavirus Disease 2019) vaccination is an opportunity for cancer patients to reduce their risk of disease and have a benign disease course. In this report, we present a benign course of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection in 68-year-old patient with metastatic lung adenocarcinoma undergoing chemoimmunotherapy who had previously received full COVID-19 vaccination. The control CT scans performed after 3 months of treatment showed partial regression of the tumor mass. On control tomography after 6 months, an intensification of fibro-consolidative changes and ground glass opacities were described. The lesions were characteristic of a history of SARS-CoV-2 infection. The neoplastic lesions described on tomography showed stabilization. After 9 months, long-term stabilization of the disease was achieved. Patients undergoing immunotherapy or chemoimmunotherapy may be at risk of developing severe COVID-19. Therefore, vaccination against SARS-CoV-2 should be strongly recommended in lung cancer patients undergoing immunotherapy. Copyright © 2022 Via Medica.

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