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1.
Int J Cancer ; 154(8): 1394-1412, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38083979

RESUMEN

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.


Asunto(s)
COVID-19 , Neoplasias , Humanos , COVID-19/epidemiología , Prueba de COVID-19 , Neoplasias/diagnóstico , Neoplasias/epidemiología
2.
Clin Exp Immunol ; 209(1): 46-63, 2022 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-35380164

RESUMEN

Increasing evidence has linked the humoral immune response with the development of various cancers. Therefore, there is growing interest in investigating the predictive value of antibodies to assess overall and tissue site-specific cancer risk. Given the large amount of antibody types and the broad scope of the search (i.e. cancer risk), the primary aim of this systematic review was to present an overview of the most researched antibodies (i.e. immunoglobulin (Ig) isotypes (IgG, IgM, IgA, and IgE), tumour and self-antigen-reactive antibodies, infection-related antibodies) in relation to overall and site-specific cancer risk. We identified various antibody types that have been associated with the risk of cancer. While no significant associations were found for IgM serum levels, studies found an inconsistent association among IgE, IgA, and IgG serum levels in relation to cancer risk. When evaluating antibodies against infectious agents, most studies reported a positive link with specific cancers known to be associated with the specific agent recognized by serum antibodies (i.e. helicobacter pylori and gastric cancer, hepatitis B virus and hepatocellular carcinoma, and human papillomavirus and cervical cancer). Several reports identified autoantibodies, as single biomarkers (e.g. anti-p53, anti-MUC1, and anti-CA125) but especially in panels of multiple autoantibodies, to have potential as diagnostic biomarkers for specific cancer types. Overall, there is emerging evidence associating certain antibodies to cancer risk, especially immunoglobulin isotypes, tumour-associated antigen-specific, and self-reactive antibodies. Further experimental studies are necessary to assess the efficacy of specific antibodies as markers for the early diagnosis of cancer.


Asunto(s)
Inmunoglobulina A , Neoplasias , Autoanticuerpos , Biomarcadores , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina E , Inmunoglobulina G , Inmunoglobulina M , Neoplasias/diagnóstico
3.
Arterioscler Thromb Vasc Biol ; 41(12): 2990-3004, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34706560

RESUMEN

OBJECTIVE: Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor treatment response. Approach and Results: We used affinity proteomics to identify EC proteins circulating in plasma that were associated with cardiovascular disease risk factor exposure. Two hundred sixteen proteins, which we previously predicted to be EC-enriched across vascular beds, were measured in plasma samples (N=1005) from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study) pilot. Thirty-eight of these proteins were associated with body mass index, total cholesterol, low-density lipoprotein, smoking, hypertension, or diabetes. Sex-specific analysis revealed that associations predominantly observed in female- or male-only samples were most frequently with the risk factors body mass index, or total cholesterol and smoking, respectively. We show a relationship between individual cardiovascular disease risk, calculated with the Framingham risk score, and the corresponding biomarker profiles. CONCLUSIONS: EC proteins in plasma could reflect vascular health status.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Endotelio Vascular/metabolismo , Proteómica/métodos , Biomarcadores/sangre , Enfermedades Cardiovasculares/patología , Endotelio Vascular/patología , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad
4.
Future Oncol ; 18(18): 2201-2216, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35382557

RESUMEN

Aim: To evaluate the impact of the pandemic on the well-being of cancer staff and determine the uptake of opt-in mitigation strategies. Materials & methods: Staff at Guy's Cancer Centre (London, UK) participated in an anonymized survey between May and August 2021. Results: Of 1182 staff, 257 (21.7%) participated. Ethnicity (p = 0.020) and comorbidity burden (p = 0.022) were associated with SARS-CoV-2 infection status. Of 199 respondents, seven (3.6%) were vaccine-hesitant, which was associated with low flu vaccine uptake (p < 0.001). Greater stress was associated with younger age (p = 0.030) and redeployment (p = 0.012). Lack of time and skepticism were barriers to using mental well-being resources. Conclusion: Albeit cautious, numerous trends the authors observed echo those in the published literature. Improved accessibility, awareness and utility of mental well-being resources are required.


COVID-19 is caused by the SARS-CoV-2 virus. The pandemic has applied immense pressure to healthcare workers, putting their physical and mental well-being at risk. However, the impact for cancer staff, specifically, is less known. In a survey of 257 cancer staff at Guy's Cancer Centre (London, UK; May­August 2021), the authors found that staff of particular ethnic groups, or with pre-existing illnesses, appeared more likely to become infected with SARS-CoV-2. Few staff were hesitant about SARS-CoV-2 vaccination, appearing more common among those not receiving the flu vaccine. For many, stress increased over time. However, barriers prevent staff from using mental well-being resources. With findings from larger studies, this work will be useful for strategies protecting cancer staff well-being.


Asunto(s)
COVID-19 , Neoplasias , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Pandemias , SARS-CoV-2 , Medicina Estatal , Vacunación
5.
Future Oncol ; 18(32): 3585-3594, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36172860

RESUMEN

Background: Few studies have investigated the long-term effects of COVID-19 on cancer patients. Materials & methods: The authors conducted a telephone survey on the long-term symptoms of cancer patients from Guy's Cancer Centre. They compared patients whose symptoms occurred/got worse over 4 weeks after COVID-19 diagnosis (classified as long COVID) with patients who did not develop symptoms or whose symptoms occurred/got worse in the first 4 weeks after diagnosis. Results: The authors analyzed responses from 80 patients with a previous COVID-19 diagnosis; 51.3% (n = 41) developed long COVID. The most common symptoms were fatigue, breathlessness and cognitive impairment. Conclusion: Findings suggest that over half of the cancer population will experience long-term effects after their initial COVID-19 diagnosis. Further studies are required to validate the findings of this study.


Asunto(s)
COVID-19 , Neoplasias , Humanos , Síndrome Post Agudo de COVID-19 , Prueba de COVID-19 , COVID-19/complicaciones , COVID-19/epidemiología , Neoplasias/complicaciones , Neoplasias/epidemiología , Disnea
6.
BMC Urol ; 22(1): 71, 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35488333

RESUMEN

BACKGROUND: Safe provision of systemic anti-cancer treatment (SACT) during the COVID-19 pandemic remains an ongoing concern amongst clinicians. METHODS: Retrospective analysis on uro-oncology patients who continued or started SACT between 1st March and 31st May 2020 during the pandemic (with 2019 as a comparator). RESULTS: 441 patients received SACT in 2020 (292 prostate, 101 renal, 38 urothelial, 10 testicular) compared to 518 patients in 2019 (340 prostate, 121 renal, 42 urothelial, 15 testicular). In 2020, there were 75.00% fewer patients with stage 3 cancers receiving SACT (p < 0.0001) and 94.44% fewer patients receiving radical treatment (p = 0.00194). The number of patients started on a new line of SACT was similar between both years (118 in 2019 vs 102 in 2020; p = 0.898) but with 53.45% fewer patients started on chemotherapy in 2020 (p < 0.001). Overall, 5 patients tested positive for COVID-19 (one asymptomatic, one mild, two moderate, one severe resulting in death). Compared to 2019, 30-day mortality was similar (1.69% in 2019 vs 0.98% in 2020; p = 0.649) whereas 6-month mortality was lower (9.32% in 2019 vs 1.96% in 2020; p = 0.0209) in 2020. CONCLUSION: This study suggests that delivery of SACT to uro-oncology patients during COVID-19 pandemic may be safe in high-incidence areas with appropriate risk-reduction strategies.


Asunto(s)
COVID-19 , Neoplasias Urológicas , Femenino , Humanos , Inmunoterapia , Masculino , Pandemias , Estudios Retrospectivos , Neoplasias Urológicas/tratamiento farmacológico
7.
Int J Cancer ; 148(4): 825-834, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33405276

RESUMEN

We investigated the association between metabolic syndrome (MetS) and its components and risk of prostate cancer (PCa) in a cohort of men enrolled in the UK Biobank. Our study cohort included 220 622 PCa-free men with baseline measurements of triglycerides (TGs), HDL-cholesterol (HDL), glycated hemoglobin (HbA1c), blood pressure (BP), and waist circumference (WC). Multivariable Cox proportional hazards regression was used to analyze associations with PCa for: individual metabolic components (TG, HDL, HbA1c, BP, WC), combinations of two and three components, and MetS overall (three or more components). We conducted mediation analyses to examine potential hormonal and inflammatory pathways (total testosterone [TT], C-reactive protein [CRP], insulin-like growth factor 1 [IGF-1]) through which MetS components may influence PCa risk. A total of 5409 men in the study developed PCa during a median follow-up of 6.9 years. We found no significant association between MetS and PCa risk (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.92-1.06). No associations were found with PCa risk and individual measurements of TG, HDL, BP, or WC. However, an inverse association was observed with elevated HbA1c (≥42 mmol/mol) (HR = 0.89, 95% CI = 0.79-0.98). Consistent inverse associations were observed between HbA1c and risk of PCa. Mediation analysis revealed TT, CRP, and IGF-1 as potential mediating factors for this association contributing 10.2%, 7.1%, and 7.9% to the total effect, respectively. Overall MetS had no association with PCa risk. However, a consistent inverse association with PCa risk was found for HbA1c. This association may be explained in part through hormonal and inflammatory pathways.


Asunto(s)
Bancos de Muestras Biológicas/estadística & datos numéricos , Biomarcadores/sangre , Síndrome Metabólico/diagnóstico , Neoplasias de la Próstata/diagnóstico , Encuestas y Cuestionarios , Adulto , Anciano , Presión Sanguínea , Proteína C-Reactiva/metabolismo , HDL-Colesterol/sangre , Estudios de Cohortes , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/complicaciones , Factores de Riesgo , Testosterona/sangre , Triglicéridos/sangre , Reino Unido , Circunferencia de la Cintura
8.
Br J Cancer ; 125(7): 939-947, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34400804

RESUMEN

BACKGROUND: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. METHODS: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. RESULTS: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). CONCLUSIONS: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.


Asunto(s)
COVID-19/epidemiología , Neoplasias Hematológicas/epidemiología , Neoplasias/epidemiología , SARS-CoV-2/patogenicidad , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , COVID-19/patología , COVID-19/virología , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/virología , Hospitales , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/patología , Neoplasias/virología , Factores de Riesgo
9.
BMC Vet Res ; 14(1): 75, 2018 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-29514653

RESUMEN

The original article [1] contains an error whereby Fig. 2a and b are mistakenly swapped with each other, and thus do not correspond to their correct respective sub-headings in the caption.

10.
BMC Vet Res ; 14(1): 35, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29390998

RESUMEN

BACKGROUND: Tutoring is a useful tool in the university teaching-learning binomial, although its development is impaired in large classes. Recent improvements in information and communication technologies have made tutoring possible via the Internet. The aim of this study was to evaluate the efficacy of mixed-method academic tutoring in two basic subjects in Veterinary Science studies at the University of León (Spain) to optimize the usefulness of tutoring support in the college environment. This quasi-experimental study was firstly carried out as a pilot study in a small group of tutored students of "Cytology and Histology" (CH) (47/186; 25.3%) and "Veterinary Pharmacology" (VP) (33/141; 23.4%) subjects, and was implemented in a large class of CH the next academic year (150 students) while comparing the results with those obtained in a previous tutorless course (162 students). Tutored students were given access to online questionnaires with electronic feedback on each subject. In addition to traditional tutoring carried out in both tutored and tutorless students, the pilot study included three sessions of face-to-face tutoring in order to monitor the progress of students. Its efficacy was assessed by monitoring students' examination scores and attendance as well as a satisfaction survey. RESULTS: Although the examination attendance rate in the pilot study was not significantly different between tutored and tutorless groups in both subjects, an increase for numerical scores in tutored groups was observed, with a significant higher final score in VP (p = 0.001) and in the CH practice exams (first term, p = 0.009; final, p = 0.023). Good and merit scores were also better in tutored students with significant differences in VP (p = 0.005). Students felt comfortable with the tutoring service (100% in CH; 91.7% in VP). Implementation of this additional support in CH also resulted in a significant increase of attendance at the final exam in tutored courses (87.3% versus 77.2%; p = 0.026), scaled (p = 0.001) and numerical scores (final score, p = 0.001). CONCLUSIONS: Online tutoring support, together with conventional teaching methods, may be a useful method to incorporate student-centered learning in basic subjects in Veterinary Science.


Asunto(s)
Educación a Distancia/métodos , Educación en Veterinaria/métodos , Enseñanza , Adolescente , Biología Celular/educación , Evaluación Educacional , Femenino , Histología/educación , Humanos , Masculino , Farmacología/educación , Proyectos Piloto , España , Estudiantes/psicología , Adulto Joven
11.
Can Vet J ; 57(12): 1247-1250, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27928170

RESUMEN

A vertebral mass in a dog with an acute onset paraparesis was identified by magnetic resonance imaging. A poorly differentiated hemangiosarcoma was diagnosed by histopathology and immunohistochemistry. Endothelial nitric oxide synthase could be a new differential marker for poorly differentiated hemangiosarcoma in dogs. Immunohistochemical detection of p53 phosphorylated at Serine392, p53, CD117, and CD44 suggest targets for design of therapeutic strategies.


Imagerie par résonance magnétique et immunistochimie d'un hémangiosarcome vertébral primaire chez un chien et répercussions pour le diagnostic et le traitement. Une masse vertébrale chez un chien atteint d'une manière soudaine d'une paraparésie a été identifiée à l'aide d'imagerie par résonance magnétique. Un hémangiosarcome mal différencié a été diagnostiqué par histopathologie et immunohistochimie. La synthase à l'oxyde nitrique endothélial pourrait être un nouveau marqueur différentiel pour l'hémangiosarcome mal différencié chez les chiens. La détection immunohistochimique de p53 phosphorylé à la sérine392, p53, CD117 et CD44 suggère des cibles pour la conception de stratégies thérapeutiques.(Traduit par Isabelle Vallières).


Asunto(s)
Neoplasias Óseas/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Hemangiosarcoma/veterinaria , Vértebras Lumbares/patología , Imagen por Resonancia Magnética/veterinaria , Neoplasias de la Columna Vertebral/veterinaria , Animales , Neoplasias Óseas/patología , Enfermedades de los Perros/patología , Perros , Hemangiosarcoma/diagnóstico , Hemangiosarcoma/patología , Inmunohistoquímica/veterinaria , Masculino , Neoplasias de la Columna Vertebral/diagnóstico , Neoplasias de la Columna Vertebral/patología
12.
Vet Dermatol ; 25(6): 538-46, e93-4, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25041412

RESUMEN

BACKGROUND: Retinoic acid (RA) and its analogues (retinoids) are promising agents in skin cancer prevention following either topical application or oral administration. However, long-term in vivo effects of RA on chemically induced hyperplastic epidermal foci in adult mouse skin have also been described, casting some doubt with regard to its chemopreventive activity. HYPOTHESIS/OBJECTIVES: To characterize chemically induced skin tumours and to investigate the in vivo long-term action and preventive effect of RA on adult mouse skin carcinogenesis. ANIMALS: Fifty-six adult Naval Medical Research Institute mice, exposed (n = 28) or not exposed (n = 28) to RA in utero. METHODS: Mice were treated with a standard two-stage skin carcinogenesis protocol, which included an initiating application of 7,12-dimethylbenz(a)anthracene followed by promotion with 12-O-tetradecanoylphorbol 13-acetate. RESULTS: Retinoic acid administered to pregnant mice showed a long-term inhibitory action on cell differentiation and development of chemically induced tumours on the adult skin of their offspring, as well as a stimulatory effect on cell proliferation and expression of an early marker of malignant progression (keratin 13). CONCLUSIONS AND CLINICAL IMPORTANCE: The results suggest that RA exposure in utero confers long-lasting effects on adult mouse skin carcinogenesis. These include chemopreventive activity (reduced number of tumours), as well as enhancement of squamous papilloma progression, which appears to be due to enhanced keratinocyte proliferation and suppression of epidermal maturation. The clinical significance of these findings is not known for other routes of RA administration at this time.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/prevención & control , Queratoacantoma/prevención & control , Papiloma/prevención & control , Neoplasias Cutáneas/prevención & control , Tretinoina/uso terapéutico , 9,10-Dimetil-1,2-benzantraceno , Animales , Carcinógenos , Carcinoma de Células Escamosas/inducido químicamente , Esquema de Medicación , Femenino , Queratoacantoma/inducido químicamente , Masculino , Ratones , Papiloma/inducido químicamente , Embarazo , Neoplasias Cutáneas/inducido químicamente , Acetato de Tetradecanoilforbol , Resultado del Tratamiento
13.
Front Oncol ; 14: 1358888, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887232

RESUMEN

Background: Rapid diagnostic clinics (RDCs) provide a streamlined holistic pathway for patients presenting with non-site specific (NSS) symptoms concerning of malignancy. The current study aimed to: 1) assess the prevalence of anxiety and depression, and 2) identify a combination of patient characteristics and symptoms associated with severe anxiety and depression at Guy's and St Thomas' Foundation Trust (GSTT) RDC in Southeast London. Additionally, we compared standard statistical methods with machine learning algorithms for predicting severe anxiety and depression. Methods: Patients seen at GSTT RDC between June 2019 and January 2023 completed the General Anxiety Disorder Questionnaire (GAD-7) and Patient Health Questionnaire (PHQ-8) questionnaires, at baseline. We used logistic regression (LR) and 2 machine learning (ML) algorithms (random forest (RF), support vector machine (SVM)) to predict risk of severe anxiety and severe depression. The models were constructed using a set of sociodemographic and clinical variables. Results: A total of 1734 patients completed GAD-7 and PHQ-8 questionnaires. Of these, the mean age was 59 years (Standard Deviation: 15.5), and 61.5% (n:1067) were female. Prevalence of severe anxiety (GAD-7 score ≥15) was 13.8% and severe depression (PHQ-8 score≥20) was 9.3%. LR showed that a combination of previous mental health condition (PMH, Adjusted Odds Rario (AOR) 3.28; 95% confidence interval (CI) 2.36-4.56), symptom duration >6 months (AOR 2.20; 95%CI 1.28-3.77), weight loss (AOR 1.88; 95% CI 1.36-2.61), progressive pain (AOR 1.71; 95%CI 1.26-2.32), and fatigue (AOR 1.36; 95%CI 1.01-1.84), was positively associated with severe anxiety. Likewise, a combination PMH condition (AOR 3.95; 95%CI 2.17-5.75), fatigue (AOR 2.11; 95%CI 1.47-3.01), symptom duration >6 months (AOR 1.98; 95%CI 1.06-3.68), weight loss (AOR 1.66; 95%CI 1.13-2.44), and progressive pain (AOR 1.50; 95%CI 1.04-2.16), was positively associated with severe depression. LR and SVM had highest accuracy levels for severe anxiety (LR: 86%, SVM: 85%) and severe depression (SVM: 89%, LR: 86%). Conclusion: High prevalence of severe anxiety and severe depression was found. PMH, fatigue, weight loss, progressive pain, and symptoms >6 months emerged as combined risk factors for both these psychological comorbidities. RDCs offer an opportunity to alleviate distress in patients with concerning symptoms by expediting diagnostic evaluations.

14.
Plant J ; 70(3): 492-500, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22171938

RESUMEN

Previous studies have demonstrated that auxin (indole-3-acetic acid) and nitric oxide (NO) are plant growth regulators that coordinate several plant physiological responses determining root architecture. Nonetheless, the way in which these factors interact to affect these growth and developmental processes is not well understood. The Arabidopsis thaliana F-box proteins TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALING F-BOX (TIR1/AFB) are auxin receptors that mediate degradation of AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) repressors to induce auxin-regulated responses. A broad spectrum of NO-mediated protein modifications are known in eukaryotic cells. Here, we provide evidence that NO donors increase auxin-dependent gene expression while NO depletion blocks Aux/IAA protein degradation. NO also enhances TIR1-Aux/IAA interaction as evidenced by pull-down and two-hybrid assays. In addition, we provide evidence for NO-mediated modulation of auxin signaling through S-nitrosylation of the TIR1 auxin receptor. S-nitrosylation of cysteine is a redox-based post-translational modification that contributes to the complexity of the cellular proteome. We show that TIR1 C140 is a critical residue for TIR1-Aux/IAA interaction and TIR1 function. These results suggest that TIR1 S-nitrosylation enhances TIR1-Aux/IAA interaction, facilitating Aux/IAA degradation and subsequently promoting activation of gene expression. Our findings underline the importance of NO in phytohormone signaling pathways.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/efectos de los fármacos , Proteínas F-Box/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Ácidos Indolacéticos/metabolismo , Óxido Nítrico/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Receptores de Superficie Celular/metabolismo , Secuencia de Aminoácidos , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Transporte Biológico , Cisteína/metabolismo , Proteínas F-Box/genética , Expresión Génica , Modelos Moleculares , Datos de Secuencia Molecular , Óxido Nítrico/análisis , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/fisiología , Plantas Modificadas Genéticamente , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteolisis , ARN de Planta/genética , Receptores de Superficie Celular/genética , Plantones/efectos de los fármacos , Plantones/genética , Plantones/crecimiento & desarrollo , Plantones/fisiología , Alineación de Secuencia , Transducción de Señal/efectos de los fármacos , Activación Transcripcional
15.
J Cancer Policy ; 31: 100316, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35559868

RESUMEN

BACKGROUND: The COVID-19 pandemic has been highly disruptive for cancer care. Here, we examined the effect COVID-19 had on performance of the 62-day Cancer Waiting Time (CWT) target set by the National Health Service (NHS) in England. METHODS: Data were retrospectively obtained on COVID-19 hospitalisations and CWT for NHS hospitals in England (n = 121). We produced a 'COVID-19 burden' to describe the proportion of each provider's beds occupied with COVID-19 patients. COVID-19 burden was examined against CWT performance for 1st April - 30th May 2020 (Wave 1), and 1st October - 30th November 2020 (Wave 2). Two-tailed Spearman correlations were used to identify relationships between COVID-19 burden and CWT performance amongst different referral (i.e., 2-week-wait (2 W W) and internal specialist) and tumour types. Significantly correlated variables were further examined using linear regression models. RESULTS: COVID-19 burden was negatively associated with the percentage of 2 W W pathway referrals that met the CWT target in Wave 1 (r= -0.30, p = 0.001) and Wave 2 (r= -0.21, p = 0.02). These associations were supported by the results from our linear regression models (B for wave 1: -0.71; 95 %CI: -1.03 to -0.40; B for wave 2: -0.38; 95 %CI: -0.68 to -0.07). No associations were found between COVID-19 burden and internal specialist referrals or tumour type. CONCLUSION: Increased COVID-19 burden was associated with lower compliance with CWT targets amongst urgent referrals from primary care in England. This will likely be an ongoing issue due to the backlog of patients awaiting investigations and treatment. POLICY SUMMARY: As the number of cancer referrals improve, we highlight the need for changes to primary and secondary care to manage the backlog within cancer diagnostic services to alleviate the impact of COVID-19.


Asunto(s)
COVID-19 , Neoplasias , COVID-19/diagnóstico , Inglaterra/epidemiología , Humanos , Neoplasias/diagnóstico , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Medicina Estatal
16.
BJUI Compass ; 3(4): 277-286, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35783588

RESUMEN

Objective: To report on the outcomes of urological cancer patients undergoing radical surgery between March-September 2020 (compared with 2019) in the European Institute of Oncology (IEO) in Milan and the South East London Cancer Alliance (SELCA). Materials and Methods: Since March 2020, both institutions implemented a COVID-19 minimal 'green' pathway, whereby patients were required to isolate for 14 days prior to admission and report a negative COVID-19 polymerase chain reaction (PCR) test within 3 days of surgery. COVID-19 positive patients had surgery deferred until a negative swab. Surgical outcomes assessed were: American Society of Anaesthesiologists (ASA) grade; surgery time; theatre time; intensive care unit (ICU) stay >24 h; pneumonia; length of stay (LOS); re-admission. Postoperative COVID-19 infection rates and associated mortality were also recorded. Results: At IEO, uro-oncological surgery increased by 4%, as compared with the same period in 2019 (n = 515 vs. 534). The main increase was observed for renal (16%, n = 98 vs. 114), bladder (24%, n = 45 vs. 56) and testicular (27%, n = 26 vs. 33). Patient demographics were all comparable between 2019 and 2020. Only one bladder cancer patient developed COVID-19, reporting mild/moderate disease. There was no COVID-19 associated mortality. In the SELCA cohort, uro-oncological surgery declined by 23% (n = 403 vs. 312) compared with the previous year. The biggest decrease was seen for prostate (-42%, n = 156 vs. 91), penile (-100%, n = 4 vs. 0) and testicular cancers (-46%, n = 35 vs. 24). Various patient demographic characteristics were notably different when comparing 2020 versus 2019. This likely reflects the clinical decision of deferring COVID-19 vulnerable patients. One patient developed COVID-19, with no COVID-19 related mortality. Conclusion: The COVID-19 minimal 'green' pathways that were put in place have shown to be safe for uro-oncological patients requiring radical surgery. There were limited complications, almost no peri-operative COVID-19 infection and no COVID-19-related mortality in either cohort.

17.
J Clin Med ; 10(8)2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33924591

RESUMEN

Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals' risk for PCa.

18.
Cancers (Basel) ; 13(21)2021 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-34771701

RESUMEN

Bilirubin has strong antioxidant properties that have been hypothesized to be preventive against the development of cancer. Thus, we aimed to investigate the association between serum total bilirubin (STB) and risk of overall and site-specific cancers in the large Swedish Apolipoprotein Mortality Risk (AMORIS) cohort. We also performed a systematic review and meta-analysis for specific cancer types (colorectal, breast and lung). We found no association between high levels of STB and risk of overall cancer. Regarding site-specific cancer, there was an inverse association between increased STB and lung cancer (Hazard Ratio (HR) for the 4th quartile (Q4) vs. Q1: 0.50; 95%CI: 0.44-0.59) and gynecological cancer (HR for Q4 vs. Q1: 0.86; 95%CI: 0.76-0.99). A positive association was found with melanoma (HR for Q4 vs. Q1: 1.25; 95%CI: 1.06-1.47) and breast cancer (HR for Q4 vs. Q1: 1.13; 95%CI: 1.01-1.25) risk. The meta-analysis showed an inverse association between high levels of STB and risk of lung cancer (Relative risk (RR): 0.69; 95%CI: 0.55-0.86). No associations were seen for colorectal and breast cancer risk. Further studies are required to establish if bilirubin can be used as a biomarker for risk assessment and/or as a novel therapeutic target.

19.
Cancers (Basel) ; 13(10)2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-34069565

RESUMEN

Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1st March and 31st July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.

20.
Cancers (Basel) ; 13(7)2021 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-33808375

RESUMEN

The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 (n = 1477 vs. 1560, respectively). Readmissions were required for 3% (n = 41), and <1% (n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% (n = 1553 vs. 2336). Readmissions were required for 11% (n = 36), <1% (n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.

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