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1.
eClinicalMedicine ; 56:101785, 2023.
Article in English | ScienceDirect | ID: covidwho-2165232

ABSTRACT

Summary Background The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings Patients were enrolled between 23 December 2020 and 31 March 2021;189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22–0.50;CCI < 2, OR: 0.38, 95% CI 0.21–0.68;suPAR > 9 ng/mL, OR: 0.35, 95% CI 0.19–0.66;suPAR 6–9 ng/mL, OR: 0.35, 95% CI 0.24–0.52;patients ≥65 years, OR: 0.41, 95% CI 0.25–0.66;and patients <65 years, OR: 0.29, 95% CI 0.19–0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28–0.57) and 0.46 (95% CI 0.32–0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment. Interpretation Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients;benefits are maintained until day 90. Funding Hellenic Institute for the Study of Sepsis;Swedish Orphan Biovitrum AB.

2.
Thrombosis Research ; 222:85-95, 2023.
Article in English | ScienceDirect | ID: covidwho-2165898

ABSTRACT

Introduction The prognostic significance of the thrombin generation assay (TGA) with a thrombomodulin (TM) challenge in patients entering hospital with severe COVID-19 is uncertain. Methods We prospectively evaluated an automated TGA (aTGA) using the ST-ThromboScreen® assay and ST-Genesia® analyser in 179 patients with severe COVID-19 during their admission to 2 university hospitals. The primary outcome was early survival at Day 28 (D28). Secondary outcomes were late survival at Day 90 (D90), later transfer to an intensive care unit (ICU), and occurrence of any thrombotic complications during hospitalisation. Results Among the 174 patients, 50 were initially admitted to ICUs. Forty-two were transferred to ICUs before D28. Fourteen patients, all in ICUs, died before D28, and 20 before D90, all but 1 in ICUs. None of the aTGA-derived results were associated with vital status either at D28 or D90. Nine patients had a thrombotic event with no association with the aTGA results. Later transfer to the ICU was associated with higher velocity index, thrombin peak height and endogenous thrombin potential (ETP) values of the aTGA performed with TM, and mainly with a lower TM-induced decrease in ETP (odds ratio 15.5 (2.15–132), p = 0.009). Conclusions aTGA, a global assay supposed to evidence coagulopathy, could predict neither early or late survival, nor thrombotic events, in hospitalised COVID-19 patients. Its clinical justification in that setting is thus unlikely. A relative resistance of the ETP to TM was associated with later transfer to the ICU and deserves further investigation.

3.
Journal of Theoretical Biology ; : 111404, 2023.
Article in English | ScienceDirect | ID: covidwho-2165642

ABSTRACT

As the Coronavirus 2019 disease (COVID-19) started to spread rapidly in the state of Ohio, the Ecology, Epidemiology and Population Health (EEPH) program within the Infectious Diseases Institute (IDI) at The Ohio State University (OSU) took the initiative to offer epidemic modeling and decision analytics support to the Ohio Department of Health (ODH). This paper describes the methodology used by the OSU/IDI response modeling team to predict statewide cases of new infections as well as potential hospital burden in the state. The methodology has two components: (1) A Dynamical Survival Analysis (DSA)-based statistical method to perform parameter inference, statewide prediction and uncertainty quantification. (2) A geographic component that down-projects statewide predicted counts to potential hospital burden across the state. We demonstrate the overall methodology with publicly available data. A Python implementation of the methodology is also made publicly available. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics”.

4.
Journal of Business Research ; 157:113608, 2023.
Article in English | ScienceDirect | ID: covidwho-2165500

ABSTRACT

This study analyzes how the resources and capabilities of the owner-manager influence the firm's capacity to survive during crises. We conceptualize that only the deliberate use of available resources (bricolage) can enhance this capacity, and that "making-do” behaviors mediate the influence of the owner's social and human resources on the firm's capacity to survive crises. Based on a sample of 462 Chilean owner-managed small and medium enterprises (SME), we test our hypotheses using a complementary partial least squares-structural equation modeling (PLS-SEM) and fuzzy set-qualitative comparative analysis (fsQCA) approach. The results indicate that when founders deliberatively use their social and cognitive resources, they enhance the firm's capacity to survive in crisis environments. The fsQCA results complement these outcomes by showing that low levels of survival capacity are related to low levels of bricolage and founders' ties.

5.
Cureus ; 14(9): e28794, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2164168

ABSTRACT

BACKGROUND/OBJECTIVE:  Acute appendicitis (AA) is predominantly managed with appendectomy, but can be treated non-operatively, leading to a high risk of recurrence. Non-operative management has been more common since the COVID-19 pandemic affected the feasibility of performing surgery. This case-control study analyzed non-operatively managed patients in order to identify clinical and radiological factors associated with recurrence risk.  Methods: Over 12 months, 48 adults with CT-proven AA managed non-operatively were identified, and followed up for at least six further months to assess them for recurrence (readmission to hospital more than 14 days after discharge and after symptom resolution, requiring treatment for appendicitis). Clinical and CT data were collected and a Cox regression survival analysis was performed to produce hazards ratios (HRs). RESULTS:  Of the 48 patients, 12 (25%) experienced a recurrence up until the end of the follow-up period, eight of whom were then treated operatively, and four treated non-operatively. On the univariate analysis, greater recurrence risk was observed in patients with diabetes mellitus, higher heart rate (on admission and maximum value during admission), lower white cell count and neutrophils and appendiceal wall thinning on CT. On the multivariate analysis, diabetes mellitus (HR=7.72, p=0.021) and higher heart rate (HR=1.08, p=0.018) were associated with statistically significant greater recurrence risk. CONCLUSIONS:  Diabetes mellitus and higher heart rate on admission are associated with greater recurrence risk of AA managed non-operatively. No CT findings were associated with statistically significant greater risk. Clinicians should, therefore, consider DM and heart rate when making decisions on appendicitis management, especially during the COVID-19 pandemic but also beyond it.

6.
Salud Uninorte ; 38(3):837-857, 2022.
Article in Spanish | Scopus | ID: covidwho-2164300

ABSTRACT

Objective: To characterize clinical indicators, comorbidity and laboratory variables associated with hospitalization and mortality in older people with Covid-19. Materials and methods: A systematic review was carried out in accordance with the PRIS-MA statement, in the Medline/Pubmed, Science databases. Direct and WOS, in which specific search strategies were applied to articles and studies that were published from the period of time between January 1, 2020 and November 26, 2020. Results: 28 articles were identified that met the the selection criteria, with a sum of the sample size of the included studies of 581,319 subjects (55.1% women). Of the factors analyzed, optimal functional status, female gender, lymphocyte count, curative use of anti-coagulants, and serum albumin levels have been associated with a better clinical prognosis in adults older than 65 years. Conclusions: Clinical characteristics, comorbidity and laboratory variables associated with hospitalization and morbidity were found. © 2022, Universidad del Norte. All rights reserved.

7.
PeerJ ; 2022.
Article in English | ProQuest Central | ID: covidwho-2164152

ABSTRACT

Introduction Acute respiratory distress syndrome (ARDS) due to Coronavirus Disease 2019 (COVID-19) causes high mortality. The objective of this study is to determine whether the arterial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2) 24 h after invasive mechanical ventilation (IMV) and the difference between PaO2/FiO2 at 24 h after IMV and PaO2/FiO2 before admission to IMV (ΔPaO2/FiO2 24 h) are predictors of survival in patients with ARDS due to COVID-19. Methods A retrospective cohort study was conducted that included patients with ARDS due to COVID-19 in IMV admitted to the intensive care unit (ICU) of a hospital in southern Peru from April 2020 to April 2021. The ROC curves and the Youden index were used to establish the cut-off point for PaO2/FiO2 at 24 h of IMV and ΔPaO2/FiO2 at 24 h associated with mortality. The association with mortality was determined by Cox regression, calculating the crude (cHR) and adjusted (aHR) risk ratios, with their respective 95% confidence intervals (95% CI). Results Two hundred patients were analyzed. The average age was 54.29 years, 79% were men, and 25.5% (n = 51) died. The cut-off point calculated for PaO2/FiO2 24 h after IMV and ΔPaO2/FiO2 24 h was 222.5 and 109.5, respectively. Those participants with a value below the cut-off point of ΔPaO2/FiO2 24 h and PaO2/FiO2 24 h after IMV had higher mortality, aHR = 3.32 (CI 95% [1.82–6.07]) and aHR = 2.87 (CI 95% [1.48–5.57]) respectively. Conclusion PaO2/FiO2 24 h after IMV and ΔPaO2/FiO2 24 h in patients diagnosed with ARDS due to COVID-19 on IMV were associated with higher hospital mortality. These findings are helpful to identify those patients with a higher risk of dying on admission to the ICU.

8.
Revista Medica de Chile ; 150(5):625-633, 2022.
Article in Spanish | EMBASE | ID: covidwho-2163842

ABSTRACT

Background: COVID-19 infection can be especially severe in certain risk populations such as patients with hematologic malignancies. Aim(s): To describe the characteristics and clinical outcomes of a population of patients with hematologic malignancies and COVID-19. Material(s) and Method(s): Review of medical records of patients with COVID-19 and hematologic malignancies, treated in Hematology Service of a regional hospital in Chile, between April 1 and October 30, 2020. Demographic characteristics, chronic comorbidities and clinical characteristics related to the underlying disease and COVID-19 infection were recorded. Result(s): Thirty adults aged 17 to 73 years (67% men) with COVID-19 confirmed by RT-PCR, were evaluated. Forty percent had comorbidities, mainly hypertension (30%), obesity (27%) and diabetes (10%). Two thirds of cases came from a nosocomial outbreak and 77% were symptomatic. Half of the cases had mild disease and 20% required mechanical ventilation. Five patients (17%) died from COVID 19. Female sex, the presence of comorbidities and obesity were more common among deceased patients. Only 1 of 5 deceased patients were in complete remission. No differences were found in the mean survival according to requirement for intubation or the presence of complete remission. Conclusion(s): This population with hematologic malignancies and COVID-19 had special characteristics leading to a greater fatality rate which, in this series, does not increase with the use of mechanical ventilation. Copyright © 2022 Sociedad Medica de Santiago. All rights reserved.

9.
BioMed Research International ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-2162052

ABSTRACT

Background. Lung squamous cell carcinoma (LUSC) has poor survival prognosis and few clinical treatment options. We urgently need to explore new therapeutic drugs in clinical practice. Cepharanthine (CEP) has been shown to have anticancer effects in several tumors, but the mechanism of CEP in treating LUSC has not been reported. Methods. SwissTargetPrediction, PharmMapper, and GeneCards were used to identify targets of CEP and LUSC. Further topological analysis was used to obtain hub genes via Cytoscape. Molecular docking was carried out to verify the combination of CEP with hub targets. Based on bioinformatics, we first analyzed the expression and survival of hub targets in LUSC and further analyzed the correlation between hub targets and cancer stemness, immune cell infiltration, and tumor mutation burden (TMB). Results. A total of 41 targets were identified. Further topological analysis identified 6 hub genes: AURKA, CCNA2, CCNE1, CDK1, CHEK1, and PLK1. Molecular docking analysis showed that CEP had stable binding to all these 6 target proteins. In-depth bioinformatics analysis of these 6 targets showed that high expression of these targets were positively correlated with cancer stemness index and negatively correlated with tumor infiltrating immune cells. In immune subtype analysis, the expressions of these targets were significantly decreased in inflammatory tumors. In addition, we also found that the expressions of these targets were positively correlated with TMB. Conclusion. Based on multidisciplinary analysis, we preliminarily identified potential targets of CEP for LUSC treatment and suggested that CEP may play a role in regulating LUSC stemness.

10.
Journal for ImmunoTherapy of Cancer ; 10(Supplement 2):A1432, 2022.
Article in English | EMBASE | ID: covidwho-2161960

ABSTRACT

Background Immune checkpoint inhibitors (ICI) revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Allocetra-OTS has an immune modulating effect on macrophages1 and showed an excellent safety profile in patients including patients with sepsis.2 Here we investigated the anti-tumoral effect of Allocetra-OTS cellular therapy, in solid tumor animal models. Methods Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis. In an immunecompetent model, Balb/c mice were inoculated intraperitoneally (IP) with AB12 (mesothelioma) with pLenti-PGK-V5-Luc-Neo and treated with anti-CTLA4 with or without Allocetra-OTS. Mice were monitored daily for clinical score and weekly using IVIS. Kaplan-Meier log rank test was done for survival. For Allocetra-OTS preparation, enriched mononuclear fractions were collected by leukapheresis from healthy eligible human donors and induced to undergo early apoptosis.To follow tumor growth in vivo, HeLa-CD19 cells were stably transduced with pLenti-PGK-V5-Luc-Neo. For CAR preparation, fresh mononuclear cells (MNC) were transfected with CD19-CAR plasmids. SCID-Bg mice were injected IP with human HeLa-CD19 or HeLa-CD19-luciferase cells, 10x10 allocetraOTS or vehicle, and 10x10 CD19-CAR T cells or mock T cells. Results In immune competent Balb/c mesothelioma model, anti-CTLA4 standalone therapy significantly improved survival from mean 34+/-9 to 44.9 +/-20 days (p<0.05). Similarly, Allocetra- OTS standalone therapy improved survival to 52.3 +/-20 days (p<0.02). However, anti-CTLA4 + Allocetra-OTS combination therapy, ameliorated survival to 86.7+/-20 days (p<0.0001) with complete cancer remission in 60-100% of mice (figure 1 & 2). Similar anti-tumoral effects of Allocetra- OTS were seen in mesothelioma model in a combination therapy with either anti-PD1 or cisplatin. In the CAR-T model, SCID-Bg mice were sacrificed or died from tumor progression in 30+/-5 days (range 27-37). CAR T cell therapy significantly improved survival to 55+/-11 days (p < 0.05 vs MOCK) but Alloctra-OTS further improved survival to 75+/-10 (p < 0.001) with 20-40% complete remission. Conclusions During IP tumor progression, Allocetra-OTS as a standalone therapy or in combination with ICI, cisplatin or CAR-T therapy, significantly reduced tumor size and resulted in complete remission in up to100% treated mice. Based on excellent safety profile in > 40 patients treated in prior clinical trials for sepsis and Covid-19, Phase I/II clinical trial of Allocetra-OTS plus chemotherapy has started and first patient already recruited. A second Phase I/II clinical trial of Allocetra-OTS plus anti-PD1, as a second- and third-line therapy in various cancers, is planned for Q4 2022.

11.
Journal for ImmunoTherapy of Cancer ; 10(Supplement 2):A1353, 2022.
Article in English | EMBASE | ID: covidwho-2161959

ABSTRACT

Background Clonal hematopoiesis (CH) is an age-related phenomenon characterized by the overrepresentation of blood cells arising from a single, mutant clone and is detectable in 10-20% of individuals over 70.1 CH has now been implicated in a variety of non-hematological disorders, such as cardiovascular diseases and Covid-19 infections, by exacerbating the innate inflammatory response.2-4 However, the impact of CH in solid tumors and response to immune checkpoint blockade (ICB) is unknown. Methods To assess the prevalence and role of CH in patients with solid tumors, we analyzed publicly available data from the MSKCC-IMPACT study.5, 6 To mechanistically study CH in solid tumors, we established an orthotopic model of pancreatic adenocarcinoma (PDAC) in mice with Tet2+/- CH. CH and WT mice were treated with either ICB (aCTLA-4 + aPD-1) or vehicle control. Single-cell (sc-) RNAseq was performed on tumor infiltrating lymphocytes (n=3/group) while remaining mice were observed for disease progression and overall survival (n=10/group). Results Analyzing CH frequencies in a cohort of patients with solid tumors, we observed that the prevalence of CH was approximately 5 times higher in patients with cancer when compared to healthy age-matched controls. Further, patients with detectable CH clones had significantly worse overall survival (figure 1A). In vivo, sc-RNAseq data revealed that myeloid cells present within the pancreatic tumors of mice with Tet2+/- CH were significantly enriched for both type I and type II interferon (IFN) signaling (figure 1B). Further, these IFN+ myeloid cells were ablated after ICB therapy in Tet2+/+ WT mice but persisted in mice with Tet2+/- CH (figure 1C). PDAC tumors from mice with Tet2+/- CH had approximately half the total number of infiltrating CD8 T cells at baseline when compared to those from Tet2+/+ WT mice. Upon ICB treatment, CD8 effector cells only expanded in the tumors from Tet2+/+ WT mice. Functionally, this translated to more rapidly progressing tumors, resistance to ICB, and reduced overall survival in mice with Tet2+/- CH (figure 1D). Conclusions CH is present in upwards of 30% of patients with solid tumors and is associated with significantly worsened prognosis. Modeling PDAC in the presence of Tet2+/- CH in vivo revealed distinct alterations in the tumor microenvironment that ultimately influenced tumor progression and response to ICB. This proposed research bridges the fields of solid tumor immunology and clonal hematopoiesis to address novel mechanisms of immunotherapy resistance that will span cancer type and, ultimately, improve patient care.

12.
Journal for ImmunoTherapy of Cancer ; 10(Supplement 2):A959-A960, 2022.
Article in English | EMBASE | ID: covidwho-2161950

ABSTRACT

Background Immunotherapy is one of the most prominent therapies for NSCLC patients. While there is a lot of promise, adverse events (AEs) due to immunotherapies are a concern. Entering the era of COVID-19, the interaction of COVID-19 vaccination status with immunotherapy is not fully understood. 1-2 As most newly diagnosed NSCLC patients will be vaccinated, understanding this interaction is important for managing their treatment. This study aims at determining whether COVID-19 vaccination status has any significant effect on AEs and outcomes of aNSCLC patients treated with immunotherapies in 1st line. Methods This retrospective study leverages ConcertAI's NSCLC Patient360TM dataset, a deeply curated real-world oncology dataset with patients from across the United States. aNSCLC patients who started 1st line treatment containing an immunotherapy at least 30 days after their last COVID-19 vaccine were included in the vaccine-primed cohort (N= 138). 1st line treatment in these patients started between January 2021 - April 2022. Similarly, a cohort of vaccine-naive patients was created by including all patients in the dataset who received their 1st line immunotherapy treatment between January 2019 - April 2020 (N=1537) to ensure none of them received COVID-19 vaccine prior to immunotherapy treatment. Descriptive analysis on these cohorts showed no significant differences in terms of age, race, gender and treatment patterns. AEs for each patient during the course of 1st line immunotherapy treatment were identified. These AEs were categorised into 5 levels (table 1). To normalise the effect of length of treatment, AE/time on immunotherapy was calculated. Progression-Free Survival (PFS) and Overall Survival (OS) from start of L1 was also compared between the two cohorts. Results 56% vaccine-naive and 54% vaccine-primed patients had an AE while on immunotherapy. The distribution of severity of AEs between the two cohorts was also quite similar (table 2). Although the AE/time was higher in the vaccinenaive cohort (p-value=0.03) (figure 1), this effect was mostly driven by 41 (2.6%) outlier patients who had many AEs in a very short span of time after starting immunotherapy. We believe such outliers were not seen in the vaccine-primed cohort primarily due to its smaller sample size. OS and PFS were similar between the two cohorts (figures 2 and 3). Conclusions COVID-19 vaccination status does not affect frequency or severity of immunotherapy related AEs or have a significant impact on patients' outcomes. As more data becomes available on the vaccine-primed cohort the impact on rarer patient sub-populations can be evaluated. (Figure Presented).

13.
International Journal of Entrepreneurial Behaviour & Research ; 28(9):448-465, 2022.
Article in English | ProQuest Central | ID: covidwho-2161313

ABSTRACT

Purpose>This paper explores the survival strategies and coping mechanisms of ethnic minority entrepreneurs operating in the hospitality sector in northern Finland during the ongoing COVID-19 pandemic.Design/methodology/approach>The paper utilizes qualitative research approach based on six exploratory case studies. The in-depth interviews in two phases were conducted with owners/mangers of ethnic minority entrepreneurial restaurants.Findings>The findings reveal that all studied case firms undertook quick adjustments in response to the COVID-19 pandemic. For example, staff working hours were reduced through mutual consultation, and readjustments to the supply chain were made so that critical ingredients remain available despite the forced lockdown and supply chain bottlenecks. However, the readjustment of the supply chain was not visible in all case firms. Some of the owner-managers who were interviewed decided to keep doing business with the ethnic minority suppliers, despite some transportation problems due to lockdowns, especially in the early phases of COVID-19. Findings also suggest that the support grants announced by the state appeared not to be particularly useful for these restaurants due to restrictive eligibility criteria that many microbusinesses potentially fail to meet. Finally, the sample microbusinesses (restaurants) entrepreneurs recognize the importance of home delivery for their business survival, although they were critical of online food delivery service providers (apps) due to their high charges. Some of the case restaurants gave customers incentives for directly ordering from them, as an alternative strategy.Originality/value>This paper is one of the first studies to specifically highlight the peculiarities of ethnic minority entrepreneurship and survival dynamics in northern Finland, where running the restaurant operations, including ensuring the supply chain management, is more complex than in the case of ethnic minority restaurants in more well-connected European countries and cities with an established history of immigrant businesses. This study is also novel in terms of specifying the strategies adopted by ethnic minority businesses in adjusting to the disruptions caused by the COVID-19 pandemic and surviving through it. At the same time, it has shown limitations and some problems associated with accessing state support announced for the hospitality industry in response to COVID-19. Finally, it offers a new angle by explicitly highlighting the power dynamics between restaurants and food ordering platforms (apps) and the potential alternatives in this specific context.

14.
Hepatology ; 76(Supplement 1):S1379-S1380, 2022.
Article in English | EMBASE | ID: covidwho-2157786

ABSTRACT

Background: Screening for hepatocellular carcinoma (HCC) is associated with earlier stage at diagnosis and longer HCC-specific survival after diagnosis, but recent studies in Veterans Affairs (VA) cohorts have reached contrasting conclusions regarding this association. Few studies have evaluated screening and overall survival. Direct-acting antivirals (DAAs) for HCV have altered the natural history of HCV cirrhosis. We evaluated screening and overall survival in the post-DAA and pre-COVID era in a national cohort of veterans with cirrhosis largely due to alcohol and HCV. Method(s): All adults in VA care with CTP A or B cirrhosis for at least 1 year prior to January 1, 2015 were followed for incident HCC and all-cause mortality through December 31, 2019. Patients were censored at development of CTP C cirrhosis or maximum follow-up. Percent of time up to date with screening (PTUDS) for eligible follow up was calculated using relevant cross-sectional imaging. Time-updating age, MELD, and comorbidity score were identified for 180-day windows. We used Cox proportional hazards regression to compare survival time after HCC diagnosis by PTUDS and logistic regression to assess 3-year all-cause mortality after HCC diagnosis. Result(s): A total of 21,441 veterans were included, of whom 4.2% developed CTP C cirrhosis, 34.3% died, and 61.6% were censored at maximum follow-up. In all, 30.3% had cirrhosis from alcohol, 24.6% from HCV, 23.4% from alcohol/HCV, and 17.7% from NAFLD. There were 2,021 incident HCCs. Adjusting for time-updating age, MELD, and comorbidities, as well as etiology of cirrhosis, race, tobacco, BMI, CTP class, and GI and PCP visit density per year of follow-up, PTUDS was associated with decreased mortality in veterans diagnosed with HCC (HR for 10% increase in PTUDS 0.90, 95% CI 0.88-0.92). Restricting to those with HCV cirrhosis, PTUDS was associated with decreased mortality in those who cleared HCV (HR=0.88, 95% CI 0.85-0.91) but not in persistently HCV positive patients (HR=0.98, 95% CI 0.95-1.02). Among veterans diagnosed with HCC by December 31, 2016, PTUDS was associated with decreased 3-year overall mortality adjusting for age, MELD, and comorbidities at time of HCC diagnosis (OR for 10% increase in PTUDS 0.76, 95% CI 0.68-0.86). Restricting to those affected by HCV, the association was stronger in those who cleared HCV (OR=0.72, 95% CI 0.62-0.84) than those persistently HCV positive (OR=0.84, 95% CI 0.71-0.99). Conclusion(s): Screening is associated with both longer survival and greater 3-year overall survival in veterans with CTP A and B cirrhosis diagnosed with HCC, in particular among those who have cleared HCV.

15.
Hepatology ; 76(Supplement 1):S1184, 2022.
Article in English | EMBASE | ID: covidwho-2157773

ABSTRACT

Background: Patients with decompensated cirrhosis and ascites are at risk for developing acute kidney injury (AKI), occurring in 20-49% of patients. Those with recurrent or refractory ascites requiring regular large volume paracentesis (LVPs) are at greater risk for AKI because of their advanced cirrhosis, abnormal hemodynamics and frequent fluid shifts from the LVPs. Aim(s): To assess the natural history of renal function in ascitic cirrhotic patients who require regular LVPs. Method(s): A single centre retrospective study including all ascitic cirrhotic patients who attended for outpatient regular LVPs from April 2020 to March 2021, excluding those with COVID infection, hepatocellular carcinoma exceeding Milan's criteria, or extensive non-liver malignancy. Data collected included demographics, paracentesis details, albumin infusions, renal function at baseline and during 3-month (M) follow-up, especially any AKI details, hospital admissions and survival. Result(s): 87 (M:57, F:30;62.0+/-11.3 yrs;MELD-Na: 17.6+/-4.8) mostly alcoholic (47%) and NASH (25%) patients who attended for regular LVPs were included. 14 patients had history of variceal bleed, 26 had a history of encephalopathy (HE). Ascites had been present for 17+/-24M at enrolment, and 12 patients had prior spontaneous bacterial peritonitis. LVP had started 9+/-11M earlier. The mean # of LVPs was 4.2+/-2.6/M with 7.3+/-2.6L of ascites removed/LVP, receiving 90.5+/-38gm/M albumin with the LVPs. The mean serum creatinine (sCr) at enrolment was 100.9+/-50.3mumol/L, with 12 patients fulfilling the KDIGO's criteria for chronic kidney disease (CKD), due to diabetes or hypertension or both. 23 patients were diagnosed to have AKI at enrolment, 3 with background CKD. 5 patients required hospital admission. Table shows the details of AKI at enrolment. During 3M follow-up, 15 episodes of AKI (stage 1: n=9, stage 2: n=6) recurred in 11 patients, with the final sCr at 3M at 113+/-90mumol/L. 17 patients had 26 admissions in 3M, mostly related to cirrhosis complications (AKI/ HRS: n=4, HE: n=4;ascites related: n=4, GI bleed: n=4;infection (n=6). There was 1 liver transplant and 7 liver related deaths. Conclusion(s): CKD is becoming common among ascitic cirrhotic patients requiring LVPs. Irrespective of CKD presence, such patients frequently develop AKI, although mostly stage 1, but recur often, leading to gradual worsening of renal function within 3 M. This subset of patients needs close monitoring and future strategies to prevent AKIs.

16.
Pakistan Journal of Medical and Health Sciences ; 16(10):182-184, 2022.
Article in English | EMBASE | ID: covidwho-2156411

ABSTRACT

Background: A hypersensitivity condition called cytokine storm is the main cause of death in COVID-19 patients. A monoclonal antibody called tocilizumab may be able to suppress the Interleukin-6 receptors (IL-6R) and lessen the likelihood that the body would have a hypersensitive immune response. Aim(s): To evaluate the mortality advantages of tocilizumab in individuals with COVID-19. Study design: Retrospective study. Place and duration of study: Bahria Town International Hospital Lahore from 16th June 2020 to 17th September 2021. Methodology: Patients with 96 confirmed instances of COVID-19 were enrolled. Two groups of patients were created. A single dosage of tocilizumab was administered to 52 participants in the first group, referred to as the survivors, and 44 patients in the second group, who passed away within 14 days. From the patients' medical records, the demographic information, co-morbid conditions, and laboratory values were obtained. The hospital's institutional review board and ethics committee (IRBEC) gave its approval for this study. The permission was ignored because this was a retroactive analysis. Result(s): 54.24 16.58 was the average age, and 54 (56.25%) of the population were men. 52 (54.16%) patients were survivors, compared to 44(45.83%) patients in the non-survivor group. In non-survivors compared to survivors, the older age group was shown to be statistically significant (62.78+/-12.86 vs. 51.65+/-11.68, p=0.003). Additionally, non-survivors had a greater BMI (p=0.006). In our study, hypertension and diabetes were the two co-morbid conditions that were most frequently detected (35.24% and 28.94%, respectively). The mortality rates among patients with diabetes, asthma, COPD, and cancer were all considerably higher (P=0.01, 0.006, and 0.004, respectively). Cancer and type-2 diabetes patients had death rates that were considerably higher (p=0.05 and p=0.01, respectively). C-reactive protein (CRP), D. Dimer, procalcitonin (PCT), and IL-6 were discovered to be the significant predictors of mortality (p 0.0001, 0.05, 0.001, and 0.004 respectively). Conclusion(s): Even though tocilizumab is authorised and has been shown to have positive results, people with diabetes, COPD, and asthma are more likely to experience negative results even after getting a single dosage of the medication. Similar to CRP, D. Dimer levels are reliable indicators of death. Copyright © 2022 Lahore Medical And Dental College. All rights reserved.

17.
J Transl Med ; 20(1):560, 2022.
Article in English | PubMed | ID: covidwho-2153602

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) severely hindered the timely receipt of health care for patients with cancer, especially female patients. Depression and anxiety were more pronounced in female patients than their male counterparts with cancer during treatment wait-time intervals. Herein, investigating the impact of treatment delays on the survival outcomes of female patients with early-stage cancers can enhance the rational and precise clinical decisions of physicians. METHODS: We analyzed five types of cancers in women from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015. Univariate and multivariate Cox regression analyses were used to determine the impacts of treatment delays on the overall survival (OS) and cancer-specific survival (CSS) of the patients. RESULTS: A total of 241,661 females with early-stage cancer were analyzed (12,617 cases of non-small cell lung cancer (NSCLC), 166,051 cases of infiltrating breast cancer, 31,096 cases of differentiated thyroid cancer, 23,550 cases of colorectal cancer, and 8347 cases of cervical cancer). Worse OS rates were observed in patients with treatment delays ≥ 3 months in stage I NSCLC ((adjusted)Hazard ratio (HR) = 1.11, 95% Confidence Interval (CI): 1.01-1.23, p = 0.044) and stage I infiltrating breast cancer ((adjusted)HR = 1.23, 95% CI 1.11-1.37, p < 0.001). When the treatment delay intervals were analyzed as continuous variables, similar results were observed in patients with stage I NSCLC ((adjusted)HR = 1.04, 95% CI 1.01-1.06, p = 0.010) and in those with stage I breast cancer ((adjusted)HR = 1.03, 95% CI 1.00-1.06, p = 0.029). However, treatment delays did not reduce the OS of patients with differentiated thyroid cancer, cervical cancer, or colorectal cancer in the early-stage. Only intermediate treatment delays impaired the CSS of patients with cervical cancer in stage I ((adjusted)HR = 1.31, 95% CI 1.02-1.68, p = 0.032). CONCLUSION: After adjusting for confounders, the prolonged time from diagnosis to the initiation of treatment (< 6 months) showed limited negative effects on the survival of most of the patients with early-stage female cancers. Whether our findings serve as evidence supporting the treatment deferral decisions of clinicians for patients with different cancers in resource-limited situations needs further validation.

18.
Medicina Clínica (English Edition) ; 2022.
Article in English | ScienceDirect | ID: covidwho-2150268

ABSTRACT

Introduction Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital. Methods We conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days. Results We studied 1122 hospitalized patients with COVID-19, whose median age was 71 years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76;95% CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32;95% CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45;95% CI: 0.28-0.73). Conclusions Our study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease. Resumen Introducción El tratamiento con estatinas podría presentar un efecto pronóstico beneficioso en pacientes con COVID-19, dadas sus propiedades inmunomoduladoras, antiinflamatorias y estabilizadoras de la placa de ateroma. Nuestro propósito fue analizar esta hipótesis tomando como base el registro de COVID-19 de un hospital universitario español. Métodos Realizamos un estudio observacional y retrospectivo en el que se incluyeron los pacientes hospitalizados con COVID-19 diagnosticado mediante PCR entre marzo de 2020 y octubre de 2020 en un centro. Mediante regresión logística, diseñamos una puntuación de propensión para estimar la probabilidad de que un paciente recibiese tratamiento con estatinas antes del ingreso. Comparamos la supervivencia de los pacientes con y sin tratamiento con estatinas mediante la regresión de Cox ponderada por la inversa de la probabilidad de recibir el tratamiento (IPT). La mediana de seguimiento fue de 406 días. Resultados Estudiamos 1.122 pacientes hospitalizados con COVID-19, cuya mediana de edad era de 71 años y de los cuales 488 (43,5%) eran mujeres. 451 (40,2%) pacientes recibían estatinas antes del ingreso. En el análisis de supervivencia ponderado por la IPT, el tratamiento previo con estatinas se asoció a una reducción significativa de la mortalidad (HR: 0,76;IC 95%: 0,59-0,97). El mayor beneficio del tratamiento previo con estatinas se observó en los subgrupos de pacientes con enfermedad arterial coronaria (HR: 0,32;IC 95%: 0,18-0,56) y enfermedad arterial extracardiaca (HR: 0,45;IC 95%: 0,28-0,73). Conclusiones Nuestro estudio mostró una asociación significativa entre el tratamiento previo con estatinas y una menor mortalidad en pacientes hospitalizados con COVID-19. El beneficio pronóstico observado fue mayor en los pacientes con enfermedad aterosclerótica coronaria o extracardiaca previa.

19.
J Thorac Cardiovasc Surg ; 2022.
Article in English | PubMed | ID: covidwho-2150219

ABSTRACT

OBJECTIVE: To understand the implications of a tiered extracorporeal membrane oxygenation (ECMO) criteria framework and the outcomes of patients with COVID-19 acute respiratory distress syndrome who we were consulted on for ECMO but ultimately declined. METHODS: All patients declined for ECMO support by a large regional health care system between March 2020 and July 2021 were included. Restrictive selection criteria were enacted midway through the study stratifying the cohort into 2 groups. Primary outcomes included 30-day mortality. Secondary outcomes included reasons for declining ECMO and survival stratified by phase. RESULTS: One hundred ninety-three patients with COVID-19 acute respiratory distress syndrome were declined for ECMO within the study period out of 260 ECMO consults. At the time of consult, 71.0% (n = 137) were mechanically ventilated and 38% (n = 74) were proned and chemically paralyzed. Thirty-day mortality was 66% (n = 117), which increased from 53% to 73% (P = .010) when restrictive criteria were enacted. Patients with multisystem organ failure, prolonged ventilator time, and advanced age had respectively an 11-fold (odds ratio, 10.6;95% CI, 1.7-65.2), 4-fold (odds ratio, 3.5;95% CI, 1.1-12.0), and 4-fold (odds ratio, 4.4;95% CI, 1.9-10.2) increase in the odds of mortality. CONCLUSIONS: Patients with COVID-19 acute respiratory distress syndrome declined for ECMO represent a critically ill cohort. We observed an increase in the severity of disease and 30-day mortality in consults in the latter phase of our study period. These findings may reflect our use of tiered selection criteria coupled with ongoing education and communication with referring centers, sparing both patients likely to respond to medical therapy and those who were unsalvageable by ECMO.

20.
HemaSphere Conference: 12th International Symposium on Hodgkin Lymphoma, ISHL ; 6(Supplement 5), 2022.
Article in English | EMBASE | ID: covidwho-2124562

ABSTRACT

The proceedings contain 115 papers. The topics discussed include: FDG-PET and serum TARC levels after one cycle of BV-AVD in advanced stage Hodgkin lymphoma patients: results from the very early pet-response adapted EORTC-COBRA trial;treatment related morbidity in patients with classical Hodgkin lymphoma: results of the ongoing, randomized phase III HD21 trial by the German Hodgkin study group;a retrospective study to evaluate the reliability of staging and risk stratification of adolescent and adult patients with Hodgkin's lymphoma registered in the lymphoma clinic at Tata Memorial Center;advanced stage classical Hodgkin lymphoma (CHL) patients with a positive interim-pet (Pet-2) Deauville Score (DS) 5 after 2 ABVD cycles: a pooled analysis of individual patient data of three multi-center trials;age, histotype and stage iv are associated with a shorter survival in patients with Hodgkin lymphoma, even the pet-adapted era. a single center retrospective study;clinical outcome of classical Hodgkin lymphoma patients receiving systemic anti-lymphoma treatment during SARS-CoV-2 positivity: results from the chemo-covid study on behalf of Fondazione Italiana Linfomi;comparative efficacy of the R-BEACOPP-14 and R-CHOP regimens in the treatment of patients with advanced stages of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) with THRLBCL-like histopathological growth patterns in the tumor biopsy;and improved overall survival with first-line brentuximab Vedotin Plus chemotherapy in patients with advanced stage III/IV classical Hodgkin lymphoma: an updated analysis of ECHELON-1.

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