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1.
Ann Surg ; 275(5): 933-939, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1883081

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.


Subject(s)
Adenoma , Carcinoma , Colonic Neoplasms , Colonic Polyps , Laparoscopy , Aged , Carcinoma/surgery , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Colonic Polyps/pathology , Colonic Polyps/surgery , Colonoscopy/methods , Female , Humans , Laparoscopy/methods , Male , Margins of Excision , Prospective Studies , Retrospective Studies
2.
Topics in Antiviral Medicine ; 30(1 SUPPL):112-113, 2022.
Article in English | EMBASE | ID: covidwho-1879939

ABSTRACT

Background: The number of cases of SARS-CoV-2 infection after BNT162b2 mRNA vaccination is significantly higher in elderly people, which has been associated to lower frequencies of SARS-CoV-2 neutralizing antibodies. Our objective was to investigate the differences in the cellular response in old and young people after the SARS-CoV-2 vaccination. Methods: Young (24-53 years, n=20) and old (70-76 years, n=20) healthy subjects vaccinated with BNT162b2 SARS-CoV-2 mRNA vaccine were studied before vaccination, two weeks after the first dose and two months after the second dose. SARS-CoV-2 (spike) specific T cell response, TLR-4 dependent monocyte response and TLR-3 dependent myeloid dendritic cell (DC) response and DC, monocyte and T-cell immunophenotype, were studied by multiparametric flow cytometry. TLR-9 dependent interferon-α (IFNα) production by PBMCs was measured by ELISA and thymic function assayed by sj/β TREC ratio using droplet digital PCR. Results: The SARS-CoV-2 specific T cell response was lower and less polyfunctional in old people. Most of the differences in CD4+ and CD8+ T cell subsets were found in degranulation (CD107a), cytokine (IFN-γ) and cytotoxic (perforin) profile (eg, Memory CD8+ perforin+;p=0.0016). The lower SARS-CoV-2 specific T cell response was associated with lower thymic function levels (eg, Memory CD4+ perforin+, r=0.631;p=0.0001). The vaccination induced a higher activation and proliferation (eg, CM CD4 HLA-DR+ p=0.002, Ki67+ p=0.019) of T cells in young people than in old ones, in addition to a higher level of homing makers to different tissues and inflammatory sites (eg, CD1c mDC integrin β7+ p=0.001, intermediate monocytes CCR2+ p=0.0003) in DCs and monocytes. Moreover, after the vaccination, old subjects showed a higher production of proinflammatory cytokines by monocytes in response to LPS (eg, IL6+;p=0.015), while young people showed a higher production of IFNα by plasmacytoid DCs after CpG-A stimulation (p=0.0009). Conclusion: The magnitude and polyfunctionality of SARS-CoV-2 specific T cell response is lower in old people, associated to a lower thymic function. In old people, the vaccination induced less immune activation and homing and the myeloid TLR-dependent response is directed towards a proinflammatory response, while in young people prevails IFNα production, related to a more effective antiviral response. These results support the additional boosting strategies in this vulnerable population.

4.
Social Policy and Society ; : 20, 2021.
Article in English | Web of Science | ID: covidwho-1852324

ABSTRACT

This article investigates the delay in implementation and inadequacy of specific policy actions in the fight against the COVID-19 pandemic in nursing homes. The analysis focuses on Lombardy and Madrid, the two wealthiest regions in Italy and Spain. These were the most severely affected by the onset of the pandemic, both country-wise and at the European level. We compare the chronology of policy decisions that affected nursing homes against the broader policy responses related to the health crisis. We look at structural factors that reveal policy legacy effects. Our analysis shows that key emergency interventions arrived late, especially when compared to similar actions taken by the national health services. Weak institutional embedding of nursing homes within the welfare state in terms of ownership, allocation of resources, regulation and coordination hindered a swift response to the onset of the crisis.

5.
Preprint in English | bioRxiv | ID: ppbiorxiv-494552

ABSTRACT

Persistent cognitive impairment and neuropsychiatric disorders are prevalent sequelae of SARS-CoV-2-induced COVID-19 in middle-aged adults. To model age-related neurological vulnerability to COVID-19, we induced respiratory SARS-CoV-2 MA10 infections by nasal inoculation in young (2 months) and middle-aged (12 months) mice. We hypothesized that aging and SARS-CoV-2 synergistically damage the blood-brain barrier (BBB). Indeed, the combined action of aging and SARS-CoV-2 infection caused more fibrinogen leakage, T cell infiltration, and neuroinflammation in middle-aged SARS-CoV-2-infected mice than in similarly inoculated young adults. Mechanistically, SARS-CoV-2 exacerbated age-related increases in Caveolin-1 BBB transcellular permeability and loss of Wnt/{beta}-catenin ligands, with no apparent changes in tight junction proteins. Finally, SARS-CoV-2 infection induced age-dependent neuropsychiatric abnormalities including bradykinesia and obsessive-compulsive-like behavior. These observations indicate that cerebrovascular aging, including loss of Wnt suppression of Caveolin-1, heightens vulnerability to SARS-CoV-2-induced neuroinflammation and neuropsychiatric sequalae. Our work suggests that modulation of Wnt signaling or its downstream effectors at the BBB could be potential interventional strategies for Long COVID. HighlightsO_LITo our knowledge, we have for the first time used a small animal model to experimentally test the impact of age on SARS-CoV-2 neuropathology. C_LIO_LIAged mice were uniquely vulnerable to neuropsychiatric signs after SARS-CoV-2 infection C_LIO_LIMiddle-age increased gliosis, cerebrovascular inflammation, BBB permeability, and T cell infiltration in SARS-CoV-2 infected mice C_LIO_LIBBB permeability was related to loss of Wnt7a suppression of Caveolin-1 C_LI

6.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333803

ABSTRACT

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic especially for low- and middle-income countries. While vaccines against SARS-CoV-2 based on mRNA and adenoviral-vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are needed to meet global demand. In this context, protein subunit vaccines formulated with appropriate adjuvants represent a promising approach to address this urgent need. Receptor-binding domain (RBD) is a key target of neutralizing antibodies (Abs) but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists, including those activating STING, TLR3, TLR4 and TLR9, alone or formulated with aluminum hydroxide (AH), and benchmarked them to AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that the AH and CpG adjuvant formulation (AH:CpG) demonstrated the highest enhancement of anti-RBD neutralizing Ab titers in both age groups (~80-fold over AH), and protected aged mice from the SARS-CoV-2 challenge. Notably, AH:CpG-adjuvanted RBD vaccine elicited neutralizing Abs against both wild-type SARS-CoV-2 and B.1.351 variant at serum concentrations comparable to those induced by the authorized mRNA BNT162b2 vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and synergistically enhanced cytokine and chemokine production in human young adult and elderly mononuclear cells. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups. ONE SENTENCE SUMMARY: Alum and CpG enhance SARS-CoV-2 RBD protective immunity, variant neutralization in aged mice and Th1-polarizing cytokine production by human elder leukocytes.

7.
Preprint in English | medRxiv | ID: ppmedrxiv-22273760

ABSTRACT

SARS-CoV-2 Omicron variants BA.1 and BA.2 seem to show reduced clinical severity. We classified 172 COVID-19 Omicron patient admissions. 66.2% of patients were admitted with primary or admission-contributing COVID-19. We therefore must be careful to base healthcare and public health decisions on the total number of hospitalized COVID-19 patients alone.

8.
12th International Conference on Innovations in Bio-Inspired Computing and Applications, IBICA 2021 and 11th World Congress on Information and Communication Technologies, WICT 2021 ; 419 LNNS:713-722, 2022.
Article in English | Scopus | ID: covidwho-1750573

ABSTRACT

This work was framed in the sanitary COVID 19 crisis, with the aim to consider the probability of access to credit, in financial institutions properly registered by the Superintendence of Banks, and Superintendence of Popular Economy and Supportive. We used the data of the Structural Company Survey of the year 2020. Through the analysis of the logistic probability in the economic sectors, was verified the commercial and manufacturing sectors have a bigger probability to access credit, making them susceptible in the financial sector, due to the critical effects created by the measures to hold the pandemic. Measures that range from governmental politics to the administrative politics of the company may attenuate the consequences. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

9.
Personnel Review ; 2022.
Article in English | Scopus | ID: covidwho-1746130

ABSTRACT

Purpose: The shift to remote work brought about by the COVID-19 pandemic dramatically limited spontaneous workplace interpersonal interactions. For one interpersonal relationship in particular, the work spouse, the sudden physical distance may impact the energy work spouses draw from one another. Drawing on interactional ritual theory, this study aims to investigate the relationship between interaction frequency and organizational outcomes mediated by relational energy amid the pandemic. Design/methodology/approach: During the COVID-19 pandemic, working adults who indicated they had a work spouse were recruited via Qualtrics to participate in a two-part online study. Findings: Complete data from 120 participants across both time periods revealed that more frequent interaction between work spouses is associated with increased job satisfaction and affective commitment mediated by relational energy. Originality/value: This study represents the first empirical examination of individual and organizational outcomes of a unique interpersonal workplace relationship. Additionally, this study enhances our understanding of the impact of relational energy in socially distanced situations between employees in a close, intimate (non-sexual) pair bond. © 2022, Emerald Publishing Limited.

10.
Journal of Managerial Psychology ; ahead-of-print(ahead-of-print):15, 2022.
Article in English | Web of Science | ID: covidwho-1722838

ABSTRACT

Purpose The purpose of this paper is to explore antecedents of helping behaviors among nurses using a social exchange framework. The paper reports an investigation into the effects of reciprocity, perceived coworker efficacy and stress on active and passive helping behaviors. Design/methodology/approach To test hypotheses, the authors performed random coefficient modeling on Mplus with data from 155 full-time nurses. Findings Nurses were willing to help coworkers regardless of perceived reciprocity levels in the relationship. Rather, their perceptions of the coworker's efficacy and previous behavior predicted helping. Originality/value This manuscript contributes to the literature in a number of ways. First, it provides empirical evidence that individuals will suppress or ignore reciprocity norms during an interdependent task. This lends credence to the idea that social exchanges may need to be examined in light of other variables or at other levels of analysis. Second, it demonstrates that investment behaviors (i.e. helping) can and do occur in exchange relationships despite low reciprocity. Overall, the data suggest that individuals are willing to maintain relationships despite a lack of returns.

12.
Probiotics Antimicrob Proteins ; 14(2): 217-223, 2022 04.
Article in English | MEDLINE | ID: covidwho-1712365

ABSTRACT

The microfilaricidal anthelmintic drug ivermectin (IVM) has been used since 1988 for treatment of parasitic infections in animals and humans. The discovery of IVM's ability to inactivate the eukaryotic importin α/ß1 heterodimer (IMPα/ß1), used by some viruses to enter the nucleus of susceptible hosts, led to the suggestion of using the drug to combat SARS-CoV-2 infection. Since IVM has antibacterial properties, prolonged use may affect commensal gut microbiota. In this review, we investigate the antimicrobial properties of IVM, possible mode of activity, and the concern that treatment of individuals diagnosed with COVID-19 may lead to dysbiosis.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Animals , Antiviral Agents , COVID-19/drug therapy , Dysbiosis/drug therapy , Ivermectin/pharmacology , Ivermectin/therapeutic use , SARS-CoV-2
13.
Journal of Vacuum Science & Technology B ; 40(2):6, 2022.
Article in English | Web of Science | ID: covidwho-1691449

ABSTRACT

The SARS-CoV-2 pandemic has had a significant impact worldwide. Currently, the most common detection methods for the virus are polymerase chain reaction (PCR) and lateral flow tests. PCR takes more than an hour to obtain the results and lateral flow tests have difficulty with detecting the virus at low concentrations. In this study, 60 clinical human saliva samples, which included 30 positive and 30 negative samples confirmed with RT-PCR, were screened for COVID-19 using disposable glucose biosensor strips and a reusable printed circuit board. The disposable strips were gold plated and functionalized to immobilize antibodies on the gold film. After functionalization, the strips were connected to the gate electrode of a metal-oxide-semiconductor field-effect transistor on the printed circuit board to amplify the test signals. A synchronous double-pulsed bias voltage was applied to the drain of the transistor and strips. The resulting change in drain waveforms was converted to digital readings. The RT-PCR-confirmed saliva samples were tested again using quantitative PCR (RT-qPCR) to determine cycling threshold (Ct) values. Ct values up to 45 refer to the number of amplification cycles needed to detect the presence of the virus. These PCR results were compared with digital readings from the sensor to better evaluate the sensor technology. The results indicate that the samples with a range of Ct values from 17.8 to 35 can be differentiated, which highlights the increased sensitivity of this sensor technology. This research exhibits the potential of this biosensor technology to be further developed into a cost-effective, point-of-care, and portable rapid detection method for SARS-CoV-2.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320223

ABSTRACT

This work reports on the design, implementation and evaluation of a survey used as a remote sanitary filter, which was applied in the Adventist Educational System of Baja California. During the SARS-CoV-2 sanitary contingency. This with the intention of acquiring information safely and in real time. Allowing to safeguard the integrity of the educational community as a whole. Accessible and easily distributed digital resources were used in order to meet the necessary requirements of distribution, acquisition and management of the information. These were adapted to the previously established communication dynamic of the educational system. The use of the survey as a sanitary filter allowed to acquire relevant health information from the student community and facilitated decision-making regarding class attendance by their tutors.These in consideration to the conditions established by educational and health authorities. Despite the short time during the design and implementation, the communication of the educational system allowed the effective distribution, application and monitoring of the digital survey. Similar strategies can be used in the follow-up during the reactivation after lockdown and to analyze social components that may be involved in these scenarios

15.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327026

ABSTRACT

SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-γ with absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalized and previously hospitalized patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalized patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses, were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 healthy donors' samples. These results have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies.

16.
Int J Cardiol ; 351: 118-125, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1670553

ABSTRACT

BACKGROUND: Cardiovascular events in the context of COVID-19 infection increase the risk of negative patient outcomes, but large cohort studies describing this association are limited. The purpose of the current study was to investigate the potential associations between cardiovascular events and mortality in patients hospitalized due to COVID-19. METHODS: A retrospective chart review was performed in 2450 patients hospitalized for confirmed COVID-19 infection within a single hospital network between March 15 and June 15, 2020. Logistic regression analysis was used to identify predictors of mortality. RESULTS: In the study population, 57% of patients had elevated high sensitivity troponin (hs-TnT) levels. Acute heart failure occurred in 23% of patients and arrhythmias were observed in 8% of patients. Of the 1401 patients with elevated hs-TnT levels, a primary cardiac etiology (e.g., myocardial infarction) was identified in 653 (47%) patients. In the remaining 748 (53%) patients, there was evidence of a primary non-cardiac etiology for hs-TnT elevation such as renal failure (n = 304) and critical illness (n = 286). Elevated hs-TnT was associated with increased risk of mortality. A significantly higher mortality rate was observed for hs-TnT elevation associated with a primary cardiac etiology (OR 4.6, 95% CI: 2.7-7.6; P < 0.001) than a primary non-cardiac etiology (OR 2.7, 95% CI: 1.6-4.5; P < 0.001). CONCLUSIONS: Elevated hs-TnT in the context of COVID-19 infection is associated with a significantly increased mortality risk. Hs-TnT elevation in the context of a primary cardiac etiology confers a nearly 2-fold higher mortality risk than hs-TnT elevation due to a primary non-cardiac etiology.


Subject(s)
COVID-19 , Troponin T , Biomarkers , Humans , Prognosis , Retrospective Studies , SARS-CoV-2
18.
Circulation ; 144(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1632416

ABSTRACT

Cardiac microthrombi are postulated to underlie cardiac injury in critical COVID-19. To determine pathogenic mechanism(s) of cardiac injury in fatal COVID-19, we conducted a single-center prospective cohort study of 69 consecutive COVID-19 decedents. Microthrombi was the most commonly detected acute cardiac histopathologic feature (n=48, 70%). We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with inhospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak ESR and CRP during hospitalization were independently associated with higher odds of microthrombi (ESR, Pnonlinearity 0.015, Passociation=0.008;CRP per 20mg/L increase, OR 1.17, 95%CI 1.00-1.36). Using single nuclei RNA-sequence analysis, we discovered an enrichment of prothrombotic, anti-fibrinolytic, and extracellular matrix signaling amongst cardiac fibroblasts in microthrombi-positive COVID-19 hearts, compared with microthrombi-negative COVID-19 hearts and non-COVID-19 donor hearts. Our cumulative findings identify these specific transcriptomic changes in cardiac fibroblasts as salient features of COVID-19-associated cardiac microthrombi.

19.
Ostaszewski, M.; Niarakis, A.; Mazein, A.; Kuperstein, I.; Phair, R.; Orta-Resendiz, A.; Singh, V.; Aghamiri, S. S.; Acencio, M. L.; Glaab, E.; Ruepp, A.; Fobo, G.; Montrone, C.; Brauner, B.; Frishman, G.; Gomez, L. C. M.; Somers, J.; Hoch, M.; Gupta, S. K.; Scheel, J.; Borlinghaus, H.; Czauderna, T.; Schreiber, F.; Montagud, A.; de Leon, M. P.; Funahashi, A.; Hiki, Y.; Hiroi, N.; Yamada, T. G.; Drager, A.; Renz, A.; Naveez, M.; Bocskei, Z.; Messina, F.; Bornigen, D.; Fergusson, L.; Conti, M.; Rameil, M.; Nakonecnij, V.; Vanhoefer, J.; Schmiester, L.; Wang, M. Y.; Ackerman, E. E.; Shoemaker, J. E.; Zucker, J.; Oxford, K.; Teuton, J.; Kocakaya, E.; Summak, G. Y.; Hanspers, K.; Kutmon, M.; Coort, S.; Eijssen, L.; Ehrhart, F.; Rex, D. A. B.; Slenter, D.; Martens, M.; Pham, N.; Haw, R.; Jassal, B.; Matthews, L.; Orlic-Milacic, M.; Senff-Ribeiro, A.; Rothfels, K.; Shamovsky, V.; Stephan, R.; Sevilla, C.; Varusai, T.; Ravel, J. M.; Fraser, R.; Ortseifen, V.; Marchesi, S.; Gawron, P.; Smula, E.; Heirendt, L.; Satagopam, V.; Wu, G. M.; Riutta, A.; Golebiewski, M.; Owen, S.; Goble, C.; Hu, X. M.; Overall, R. W.; Maier, D.; Bauch, A.; Gyori, B. M.; Bachman, J. A.; Vega, C.; Groues, V.; Vazquez, M.; Porras, P.; Licata, L.; Iannuccelli, M.; Sacco, F.; Nesterova, A.; Yuryev, A.; de Waard, A.; Turei, D.; Luna, A.; Babur, O.; Soliman, S.; Valdeolivas, A.; Esteban-Medina, M.; Pena-Chilet, M.; Rian, K.; Helikar, T.; Puniya, B. L.; Modos, D.; Treveil, A.; Olbei, M.; De Meulder, B.; Ballereau, S.; Dugourd, A.; Naldi, A.; Noel, V.; Calzone, L.; Sander, C.; Demir, E.; Korcsmaros, T.; Freeman, T. C.; Auge, F.; Beckmann, J. S.; Hasenauer, J.; Wolkenhauer, O.; Willighagen, E. L.; Pico, A. R.; Evelo, C. T.; Gillespie, M. E.; Stein, L. D.; Hermjakob, H.; D'Eustachio, P.; Saez-Rodriguez, J.; Dopazo, J.; Valencia, A.; Kitano, H.; Barillot, E.; Auffray, C.; Balling, R.; Schneider, R.; Community, Covid- Dis Map.
Molecular Systems Biology ; 17(12):2, 2021.
Article in English | Web of Science | ID: covidwho-1589729
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