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1.
Vaccimonitor (La Habana, Print) ; 30(2): 69-80, mayo.-ago. 2021. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1252326

RESUMEN

RESUMEN Este reporte corresponde al análisis de la calidad de vida de los pacientes que se incluyeron en el ensayo clínico fase III de evaluación de la vacuna CIMAvaxEGF® en cáncer de pulmón de células no pequeñas. La calidad de vida se evaluó empleando los cuestionarios EORTC QLQ-C30 y QLQ-C13, al inicio y cada 3 meses hasta el fallecimiento del paciente a criterio del investigador. Para comparar las medianas entre los dos grupos se utilizó la prueba no paramétrica de Mann-Whitney. Las comparaciones entre el nivel basal y los diferentes tiempos de seguimiento se realizaron a través de la prueba no paramétrica de Wilcoxon. El cuestionario QLQ-C30 evidenció un beneficio en cuanto a calidad de vida para el grupo vacunado con la vacuna CIMAvaxEGF® en las escalas funcionales (global, rol y social), en las escalas de síntomas de la enfermedad y del tratamiento (dolor) se observó que mejora la calidad de los mismos a favor de los pacientes tratados con la vacuna CIMAvaxEGF®. El cuestionario QLQ-C13, también evidenció ventajas para el grupo vacunado desde el punto de vista de beneficio clínico en los síntomas (disnea, disfagia, alopecia y dolor en el pecho). Se señala como significativo que disminuye la hemoptisis y la tos en el grupo vacunado, observándose un empeoramiento en el grupo control.


ABSTRACT This report corresponds to quality of life analysis of patient with non-small cell lung cancer included in the phase III clinical trials Evaluation of CIMAvaxEGF® vaccine in lung cancer. The quality of life was evaluate using the EORTC questionnaires QLQ-C30 y QLQ-C13, at the beginning and every 3 months. To compare the median between two groups the Mann-Whitney non-parametric test was used. To compare the baseline and different follows times the Wilcoxon non-parametric test was used. The QLQ-C30 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the functional scores (global, role and social) and symptoms of the disease (pain). The QLQ-LC13 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the symptoms scores (dyspnea, dysphagia, alopecia and chest pain). It is noted as significant that the hemoptysis decreases in the group vaccinated as well as the dysphagia, the cough and the dyspnea observing a worsening in the control group.

2.
Am J Clin Oncol ; 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34091475

RESUMEN

OBJECTIVE: The objective of this study was to evaluate the impact of body mass index (BMI) on overall survival, freedom from distant metastases, rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. MATERIALS AND METHODS: Three hundred forty consecutive, prospectively evaluated AS patients underwent a staging transperineal template-guided mapping biopsy before AS enrollment and were stratified by BMI (<25, 25 to 29.9, 30 to 34.9, and >35 kg/m2). Evaluated outcomes included overall survival, freedom from distant metastases, TI, QOL to include urinary, bowel, sexual function and depression and serial postvoid residual urine measurements. The relationship between BMI and anterior prostate cancer distribution was evaluated. Repeat biopsy was based on prostate specific antigen kinetics, abnormal digital rectal examination and patient preference. RESULTS: Of the 340 patients, 323 (95%) were Gleason 3+3 and 17 patients (5.0%) were Gleason 3+4. The median follow-up was 5.2 years (range: 1 to 14 y). At 10 years, TI was instituted in 4.7%, 2.2%, 9.5%, and 25.0% of patients in BMI cohorts <25, 25 to 29.9, 30 to 34.9, and ≥35 (P=0.075). No patient has developed distant metastases. The median time to TI was 4.86 years. In multivariate analysis, TI was most closely predicted by prostate specific antigen density (P=0.071). At 8 years, no statistical differences in urinary function, bowel function, depression or postvoid residual were noted. However, a trend for erectile dysfunction was identified (P=0.106). CONCLUSION: At 10 years, BMI did not statistically predict for TI, geographic distribution of prostate cancer or QOL parameters.

4.
Inflammation ; 2021 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-34091823

RESUMEN

Gasdermins (GSDM) are members of a family of pore-forming effector proteins which lead to membrane permeabilization and pyroptosis, a lytic cell death with pro-inflammatory characteristics. Recently, two members of the gasdermin family, gasdermin B (GSDMB) and gasdermin E (GSDME), were shown to suppress tumor growth, through the involvement of cytotoxic lymphocytes. Other studies also reported the important functions of gasdermins in various cancer types including gastric cancer, hepatocarcinoma, and cervix and breast cancer. However, gasdermins have not been previously studied in the context of serous ovarian cancer. Here, we showed that gasdermin D (GSDMD) and gasdermin C (GSDMC) expression increases in serous ovarian cancer; in contrast, the expression of GSDME and PJVK (Pejvakin, DFNB59) is downregulated, compared to healthy ovaries, in multiple independent gene expression datasets. We found that copy number gains are highly frequent (present in approximately 50% of patients) in genes encoding GSDMD and GSDMC in ovarian cancer, in line with their upregulated expression in serous ovarian cancer. Moreover, we observed that the expression of GSDMB and GSDMD, but not of GSDME, is different among several histotypes of epithelial ovarian cancer. Therefore, we propose that differential expression and copy number variations of certain gasdermins might be associated with the development of serous ovarian cancer, in which different members of the family have distinct functions; however, further research is required in in vivo models to understand how changes in gasdermin family members mechanistically contribute to serous ovarian cancer.

5.
BJU Int ; 2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34092021

RESUMEN

BACKGROUND: To report the health-related quality of life (HRQoL) after robotic assisted radical cystectomy and intracorporeal urinary diversion (iRARC) and to identify factors impacting on return to baseline. PATIENTS AND METHODS: Consecutive patients undergoing iRARC between January 2016 - December 2017 completed the EORTC-QLQ-C30 and EORTC-QLQ-BLM30 questionnaires before surgery and had a minimum of 12 months follow-up postoperatively. RESULTS: A total of 76 patients met the inclusion criteria at 12 months. Neobladder (NB) cases (n = 24) were younger (57.0 years vs 71.0 years, p <0.001) and fitter than ileal conduit (IC) cases (n = 52) and had higher physical (100.0 vs 93.3, p = 0.039), and sexual functioning (66.7 vs 50.0, p = 0.013) scores at baseline. Longitudinal analysis of the EORTC-QLQ-C30 showed that physical (NB: 93.3 vs 100.0, p=0.020; IC: 80.0 vs 93.3, p<0.001) and role functioning scores (NB: 83.3 vs 100.0, p=0.010; IC: 83.3 vs 100.0, p=0.017) decreased and fatigue score (NB: 22.2 vs 11.1, p=0.026; IC: 33.3 vs 22.2, p = 0.008) increased at 3 months in both diversion groups. Scores returned to baseline at 6 months except physical functioning score in ileal conduit patients that remained below baseline till 12 months (86.7 vs 93.3, p=0.012). Global HRQoL score did not show significant change postoperatively in both groups. A major 90-day Clavien-Dindo complication was a significant predictor (OR: 0.11, CI: 0.02-0.62, p=0.012) of deteriorated global HRQoL score at 3 months, while occurrence of a late complication (OR: 0.14, CI: 0.03-0.65, p=0.013) was predictor of deteriorated global HRQoL score at 12 months. Longitudinal analysis of the EORTC-QLQ-BLM30 showed that urinary problems (NB: 14.3 vs 38.3, p<0.001; IC: 5.6 vs 19.1, p<0.001) and future perspective (NB: 33.3 vs 44.4, p=0.004; IC: 22.2 vs 44.4, p<0.001) scores were better than baseline at 3 months. Sexual function deteriorated significantly at 3 months (NB: 8.3 vs 66.7, p<0.001; IC: 4.2 vs 50.0, p<0.001) , then showed improvement at 12 months but was still below baseline (NB: 33.3 vs 66.7, p=0.001; IC: 25.0 vs 50.0, p<0.001). Involvement in penile rehabilitation was shown to be a significant predictor (ß: 18.62, CI: 6.06-30.45, p=0.005) of higher sexual function score at 12 months. CONCLUSION: While most functional domains and symptoms scales recover to or exceed baseline within 6 months after iRARC, physical function remains below baseline in ileal conduit patients up to 12 months. Global HRQoL is preserved for both types of urinary diversion, however, postoperative complications seem to be the main driving factor for global HRQoL. Sexual function is adversely affected after iRARC suggesting that structured rehabilitation of sexual function should be an integral part of cystectomy pathway.

6.
Palliat Med ; 35(6): 1158-1169, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34092140

RESUMEN

BACKGROUND: Comparative effectiveness of different types of palliative homecare is sparsely researched internationally-despite its potential to inform necessary decisions in palliative care infrastructure development. In Germany, specialized palliative homecare delivered by multi-professional teams has increased in recent years and factors beyond medical need seem to drive its involvement and affect the application of primary palliative care, delivered by general practitioners who are supported by nursing services. AIM: To compare effectiveness of primary palliative care and specialized palliative homecare in reducing potentially aggressive interventions at the end-of-life in cancer and non-cancer. DESIGN: Retrospective population-based study with claims data from 95,962 deceased adults in Germany in 2016 using multivariable regression analyses. SETTINGS/PARTICIPANTS: Patients having received primary palliative care or specialized palliative homecare (alone or in addition to primary palliative care), for at least 14 days before death, differentiating between cancer and non-cancer patients. RESULTS: Rates of potentially aggressive interventions in most indicators were higher in primary palliative care than in specialized palliative homecare (p < 0.01), in both cancer and non-cancer patients: death in hospital (odds ratio (OR) 4.541), hospital care (OR 2.720), intensive care treatment (OR 6.749), chemotherapy (OR 2.173), and application of a percutaneous endoscopic gastrostomy (OR 4.476), but not for parenteral nutrition (OR 0.477). CONCLUSION: Specialized palliative homecare is more strongly associated with reduction of potentially aggressive interventions than primary palliative care in the last days of life. Future research should identify elements of specialized palliative homecare applicable for more effective primary palliative care, too. German Clinical Trials Register (DRKS00014730).

7.
Palliat Support Care ; : 1-8, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34092275

RESUMEN

OBJECTIVES: To use data from a national quality register to investigate if there are differences relating to migrant background in the quality of end-of-life care of patients dying in Sweden. METHODS: A retrospective, comparative register-based study. In total, 81,418 deceased patients, over 18 years of age, registered in the Swedish Register of Palliative Care during 2017 and 2018, of expected death were included in the study. Of these, 72,012 were Swedish-born and 9,395 were foreign-born. Descriptive and analytical statistical methods were used. RESULTS: No general pattern of differences in quality regarding end-of-life care was found between Swedish- and foreign-born patients. There were several significant differences in various quality indicators but not in a specific direction. Sometimes, the quality indicators showed an advantage for Swedish-born patients but just as often, they were also favorable for foreign-born patients. Swedish-born patients had greater access to specialized palliative care than foreign-born patients. Foreign-born patients were more often cared for in general home care setting, despite a higher frequency of cancer diagnosis. SIGNIFICANCE OF RESULTS: Foreign-born patients were less likely to be cared for in specialized palliative care units and had poorer access to palliative care teams than Swedish-born patients, despite having a higher proportion of cancer diagnoses. However, no general pattern was found indicating that foreign-born patients were disadvantaged in the quality indicators measured in the present study. Perhaps, this is an indication that the palliative care in Sweden is individualized; nonetheless, the quality of end-of-life care would be higher if dying patients, regardless of country of birth, have better access to specialized palliative care.

8.
Artículo en Inglés | MEDLINE | ID: mdl-34063167

RESUMEN

Using path modeling, this study aimed to explore whether mental adjustment was directly or indirectly related to comprehensive quality of life outcome (CoQoLO) among patients with terminal cancer. We conducted a cross-sectional designed study among patients with terminal cancer who underwent convenience sampling at our northern Taiwan clinic from August 2019 to August 2020. Patient characteristics data were collected via structured questionnaires, namely, the Mini-Mental Adjustment to Cancer Scale and the Comprehensive Quality of Life Outcome Inventory. Descriptive statistics and regression analyses were used to examine the relationship between mental adjustment and CoQoLO. Path analysis described the dependencies among variables. For the 117 enrolled patients analyzed, MAC (ß = 1.2, 95% confidence interval (CI) = 0.8-1.6, p < 0.001) and living with others (ß = 19.9, 95% CI = 4.1-35.7, p = 0.015) were significant predictors and correlated positively with a CoQoLO score. Path modeling showed that the patients' mental adjustment, economic status, perceived disease severity, palliative prognostic index, and symptom severity directly affected their CoQoLO. Our results indicate that the higher the mental adjustment, the better the CoQoLO among patients with terminal cancer. Thus, nurses need to assess mental adjustment levels when patients are hospitalized and accordingly develop interventions to improve the terminally ill patients' mental adjustment to the final stages of cancer, thereby helping them to achieve good CoQoLO.

9.
Artículo en Inglés | MEDLINE | ID: mdl-34064433

RESUMEN

The physical environment of a treatment centre may impact the well-being of patients and their perceptions of care. Outpatients with haematological cancer may be in contact with the treatment centre over long periods and could be particularly affected. This study aimed to identify haematological cancer patients' perceptions of supportive design elements in the hospital they attended and associations with self-reported mood or well-being. Outpatients from three large metropolitan hospitals in Australia were mailed a self-report questionnaire and responded to statements about the treatment centre concerning their sense of control over the physical surroundings; access to social support; and access to positive distractions. Participants also reported whether they felt the overall environment affected their mood or wellbeing. Of the outpatients who returned the questionnaire (n = 165), almost one-quarter (24%) agreed that the physical environment of the hospital affected their mood or well-being. Patients who disagreed that the hospital was a comfortable temperature or agreed that waiting rooms were crowded had significantly higher odds of reporting that the treatment environment affected their mood or wellbeing. Implementing systems to reduce overcrowding in waiting rooms and increasing patient control over personal temperature in clinics may be the most effective strategies to improve patient wellbeing.

11.
Sci Rep ; 11(1): 12170, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34108513

RESUMEN

Acute appendicitis is a rare gastrointestinal complication of anti-cancer chemotherapy and hematopoietic stem cell transplantation. Among a cohort of 2341 hemato-oncologic patients at a pediatric tertiary care cancer center, we identified 21 patients (0.9%) with 23 episodes of acute appendicitis, based on pathological imaging of the appendix and clinical findings. Median age at diagnosis was 10.21 years. Types of underlying disease included acute leukemias (n = 15), solid tumors (n = 4), and aplastic anemia (n = 2). Clinical symptoms seen in > 1 case were recorded for all 23 episodes as follows: abdominal pain, n = 22; abdominal tenderness, n = 4; fever, n = 7; nausea, n = 2; emesis; n = 2; diarrhea, n = 5; and constipation, n = 2. Median leukocyte count at diagnosis was 0.5 × 109/L, with a median of 0.1 × 109/L for the absolute neutrophil count (ANC). All patients received broad-spectrum antibiotics and 18/23 (78%) patients underwent uneventful appendectomy after a median of 5 days and with a median ANC of 0.7 × 109/L. Median duration until continuation of chemotherapy was 17 days for the 20 cases of appendicitis occurring during the patients' disease course. Overall, 5/21 (19%) patients died including one related to the appendicitis itself which progressed to a typhlitis and was due to a fungal infection. The other fatalities were transplant- (n = 2) and leukemia-related (n = 2). Acute appendicitis is a rare and usually not life-threatening event in pediatric hemato-oncologic patients, which, if managed by prompt administration of broad-spectrum antibiotics (and antimycotics), can be safely followed by an elective (delayed) appendectomy, even before complete recovery of the neutrophils is achieved.

12.
PLoS One ; 16(6): e0253018, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34111218

RESUMEN

BACKGROUND: Men with a newly diagnosed prostate cancer are often treated by surgery. The time window between cancer diagnosis and surgery causes high levels of uncertainty and stress, which negatively impact quality of life (QoL). We previously reported a larger intervention pilot study which demonstrated that participation in a community-based pre-operative exercise programme significantly improved physical fitness and health-related quality of life in men with prostate cancer prior to surgery. The aim of the current pilot study was to get an insight into men's perceptions of wellbeing and QoL following completion of the pre-operative exercise programme. METHODS: From November 2017 to June 2018, men scheduled for prostate cancer surgery were recruited and took part in a prescribed community-based pre-operative exercise programme in the time available between referral and surgery. Following completion of the pre-operative exercise programme (within 1 week before surgery), participants took part in one semi-structured interview which explored four broad QoL domains: physical, psychological, social, and spiritual wellbeing. Data were analysed using thematic analysis (a bottom up/inductive analysis). RESULTS: Eleven men were recruited: mean standard deviation (SD) age was 60 ± 7 years. Data supported four main themes. Participation in the community-based pre-operative exercise training programme (over a mean (SD) of 4 ± 2 weeks) provided participants with: 1) a teachable moment; 2) a journey of preparation; 3) a sense of optimism; and 4) social connectedness prior to surgery. CONCLUSION: This study provides an insight into how the exercise programme impacted wellbeing and QoL in men preparing for prostate cancer surgery. These findings highlight the important role that exercise prehabilitation plays for men preparing for prostate cancer surgery. Such exercise programmes can be easily implemented into standard cancer pathways by establishing relationships between hospital teams and community exercise programmes.

13.
Support Care Cancer ; 2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34114098

RESUMEN

PURPOSE: Cancer-related biopsychosocial distress is highly prevalent across the cancer care continuum. The implementation of screening patients for biopsychosocial distress has become a standard of practice in cancer care. With the presence of COVID-19, clinical care has shifted from in-person care to virtual care in many instances. One of the realities of COVID-19 is the significant decrease in screening patients for biopsychosocial symptom burden. METHODS: Given that screening for distress has become an accreditation standard in many cancer programs, in the province of Alberta, Canada, all patients are screened for distress with every visit to the cancer centre. Given the presence of COVID-19, much of cancer care has shifted to being delivered virtually (through mediums such as Zoom). In this paper, we present pre- and post-COVID data on the frequency of distress screening and its impact on patient care. RESULTS: A review of pre- and post-COVID-19 screening for distress questionnaires revealed that patients who received virtual care were less satisfied in the areas of emotional support and received less resources and referrals to supportive care. CONCLUSION: The rapid integration of virtual care without the inclusion of a standardized distress screening tool was akin to a natural experiment, as two groups (virtual and in-person clinic patients) received different levels of care and interventions. Without the inclusion of distress screening, the clinical conversation around symptoms is less likely to occur and results in fewer referrals to best practices in supportive care services. Lessons learned about virtual cancer care without distress screening in the time of COVID-19 demonstrates significantly fewer patients being screened for distress and subsequently has resulted in less supportive care referrals. Going forward, we must find ways to ensure that virtual cancer care continues to support distress screening and best patient-centric care.

14.
Artículo en Inglés | MEDLINE | ID: mdl-34118370

RESUMEN

CONTEXT: Family functioning is a modifiable factor associated with major depressive disorder (MDD) and complicated grief (CG) among the bereaved families of patients with advanced cancer; however, the evidence regarding this association is limited. OBJECTIVES: We aimed to explore the association of family functioning with possible MDD and CG among the bereaved families of patients with advanced cancer who died in palliative care units. METHODS: This study is a part of the J-HOPE4 study, a nationwide cross-sectional multi-purpose questionnaire survey conducted in 2018. We recruited potential participants from 164 inpatient palliative care units in Japan and assessed family functioning with the Family Relations Index (FRI). Family functioning was classified into three categories (Well-functioning: FRI≧10, Intermediate: FRI=8〜9, Dysfunctioning≦7). The Patient Health Questionnaire 9 (PHQ-9) and the Brief Grief Questionnaire (BGQ) were used to assess depression (PHQ-9 score≧10) and complicated grief (BGQ score≧8), respectively. Multinomial logistic regression analysis was performed with the possible MDD and CG and factors the family functioning. RESULTS: A total of 615 questionnaires were returned, of which the 54.0 % (n=510) age of questionnaires could be used. Although family functioning was associated with possible MDD (21.1% in Dysfunctional; 9.3% in Well-functional, P=0.016), it was not associated with possible CG (14.8% in Dysfunctional; 9.9% in Well-functional, P=0.929). Possible MDD and CG were significantly associated with deteriorated family relationships (OR:8.29; P=0.004 and OR:34.00; P<0.001, respectively), and consulting with health care providers about their concerns (OR:0.23; P=0.003 and OR:0.23; P=0.003, respectively). CONCLUSIONS: Family function was affected by post-bereavement possible MDD and not by CG. Our findings suggest that health care providers can identify risk factors for MDD among bereaved, dysfunctional family members.

15.
Artículo en Inglés | MEDLINE | ID: mdl-34118371

RESUMEN

CONTEXT: The integration of palliative care into standard oncologic care has been shown to improve multiple outcomes in patients with advanced cancer. Ideal methods for integrating these disciplines is an ongoing area of discussion. One method of integration is a palliative oncology tumor board (POTB). OBJECTIVES: To describe the implementation of a POTB in a community cancer center as a method of integrating oncology and palliative care by providing a forum for multidisciplinary discussion of complex cases. METHODS: During development of the POTB, multiple influencing factors and barriers were considered including the setting of implementation, culture prior to implementation, design elements, engagement of stakeholders and evaluation of implementation. The focus of this POTB was to address the identified communication gap between inpatient and outpatient care teams. Two complex hospitalized oncology patients were selected to be discussed weekly. RESULTS: Conferences were attended by an average of 23 individuals. The highest proportion of attendees were members of oncology support services (OSS; 31%), followed by medical oncology (25%). The most common theme of discussion was methods of communication with patient and/or family (68% of cases). Thirty days after presentation, a total of 50 new referrals were placed to inpatient palliative care, OSS and outpatient palliative care and 11 new advance care plans were documented in the electronic medical record. CONCLUSION: This paper describes a sustainable method to implement a POTB in a community cancer center setting, which is one method of integrating palliative care into standard oncologic care.

16.
JMIR Res Protoc ; 10(6): e26264, 2021 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-34114954

RESUMEN

BACKGROUND: In hereditary breast and ovarian cancer (HBOC), family communication of genetic test results is essential for cascade genetic screening, that is, identifying and testing blood relatives of known mutation carriers to determine whether they also carry the pathogenic variant, and to propose preventive and clinical management options. However, up to 50% of blood relatives are unaware of relevant genetic information, suggesting that potential benefits of genetic testing are not communicated effectively within family networks. Technology can facilitate communication and genetic education within HBOC families. OBJECTIVE: The aims of this study are to develop the K-CASCADE (Korean-Cancer Predisposition Cascade Genetic Testing) cohort in Korea by expanding an infrastructure developed by the CASCADE (Cancer Predisposition Cascade Genetic Testing) Consortium in Switzerland; develop a digital health intervention to support the communication of cancer predisposition for Swiss and Korean HBOC families, based on linguistic and cultural adaptation of the Family Gene Toolkit; evaluate its efficacy on primary (family communication of genetic results and cascade testing) and secondary (psychological distress, genetic literacy, active coping, and decision making) outcomes; and explore its translatability using the reach, effectiveness, adoption, implementation, and maintenance framework. METHODS: The digital health intervention will be available in French, German, Italian, Korean, and English and can be accessed via the web, mobile phone, or tablet (ie, device-agnostic). K-CASCADE cohort of Korean HBOC mutation carriers and relatives will be based on the CASCADE infrastructure. Narrative data collected through individual interviews or mini focus groups from 20 to 24 HBOC family members per linguistic region and 6-10 health care providers involved in genetic services will identify the local cultures and context, and inform the content of the tailored messages. The efficacy of the digital health intervention against a comparison website will be assessed in a randomized trial with 104 HBOC mutation carriers (52 in each study arm). The translatability of the digital health intervention will be assessed using survey data collected from HBOC families and health care providers. RESULTS: Funding was received in October 2019. It is projected that data collection will be completed by January 2023 and results will be published in fall 2023. CONCLUSIONS: This study addresses the continuum of translational research, from developing an international research infrastructure and adapting an existing digital health intervention to testing its efficacy in a randomized controlled trial and exploring its translatability using an established framework. Adapting existing interventions, rather than developing new ones, takes advantage of previous valid experiences without duplicating efforts. Culturally sensitive web-based interventions that enhance family communication and understanding of genetic cancer risk are timely. This collaboration creates a research infrastructure between Switzerland and Korea that can be scaled up to cover other hereditary cancer syndromes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04214210; https://clinicaltrials.gov/ct2/show/NCT04214210 and CRiS KCT0005643; https://cris.nih.go.kr/cris/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/26264.

17.
Environ Mol Mutagen ; 2021 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-34115413

RESUMEN

Telomerase is a ribonucleoprotein enzyme that synthesizes telomere end sequence. The expression of hTERT gene, encoding the catalytic subunit of human telomerase, is restricted to highly proliferative tissues and is undetectable in most somatic cells. Abnormal activation of hTERT gene is found in 90% of human tumors. Previously, we identified tandem repeat of 42-bp/unit, VNTR2-1, in intron 2 of the hTERT gene, as a novel regulatory element important for hTERT transcription in cancer cells. In the current study, we found that multiple 42-bp repeats of VNTR2-1 activated luciferase gene in reporter plasmids. Mutation of the predicted cis-regulatory elements within the 42-bp repeats, including a E-box motif, resulted in a partial or complete loss of its enhancer activity. Moreover, MYC family proteins, c-MYC, MAX, and MNT, regulated hTERT gene transcription through both VNTR2-1 and E-boxes at the proximal hTERT promoter. Chromatin segmentation analysis of published ChIP-sequencing data from K562 cells indicated that VNTR2-1 was a bivalent enhancer. In telomerase-expressing human melanoma cell line MelJuSo, deletion of VNTR2-1 caused the hTERT promoter chromatin status to change from an active state to a repressed state, accompanied by increases of H3K27me3 and H3K9me3 marks. Therefore, we provided additional evidence for VNTR2-1 as a functional regulatory element that regulated hTERT expression by MYC family transcription factors. These results have improved our knowledge on the functions of repetitive genomic DNAs and the regulatory mechanisms of human telomerase gene. This article is protected by copyright. All rights reserved.

18.
Int J Paediatr Dent ; 2021 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-34115428

RESUMEN

BACKGROUND: Oral mucositis (OM) is an important side effect related to allogeneic hematopoietic stem cell transplantation (allo-HSCT) and it has been associated with a significative reduction of quality of life. A negative impact of this toxicity in pediatric patients could result in an increased use of parenteral feeding and opioids, longer periods of hospitalization and higher risk of systemic infection. AIM: To investigate the clinical features, and clinical outcomes associated with OM development and severity in hematologic cancer pediatric patients undergoing allo-HSCT who underwent professional dental care (PDC) and photobiomodulation (PBM) as prophylactic treatment. DESIGN: Medical data and OM presentation were retrieved retrospectively from all patients younger than 18 years who were submitted to allo-HSCT between 2013-2016. The incidence of OM was assessed and graded by two oral medicine specialists following the WHO guidelines and it was correlated with clinical parameters. RESULTS: Forty-nine consecutive pediatric patients were included. OM was diagnosed in 73.5% of patients, and in 36.1% of patients OM was classified as severe. Acute lymphoblastic leukemia as a primary diagnosis and the use of a myeloablative regimen were associated with OM development. The primary diagnosis and use of Total Body Irradiation (TBI) were associated with aggressive OM. Neither the incidence nor the severity of OM affected the overall survival, whereas only the use of a myeloablative regimen and a high body mass index (BMI) were determinants of lower OM-free survival rates. CONCLUSION: Myeloablative conditioning and a high BMI were observed to be independent prognostic determinants of a lower OMFS rate. The cluster analysis allowed us to outline patient profiles with greater susceptibility to the development and severity of oral mucositis which seems to be an useful tool to determine the risk of OM in pediatric patients.

19.
Eur J Cancer ; 152: 204-214, 2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34119924

RESUMEN

AIM: To investigate the health-related quality of life (HRQOL) of Dutch adult childhood cancer survivors (CCS) and to identify risk factors of impaired HRQOL. METHODS: Adult CCS (age >18, diagnosed <18, ≥5 years since diagnosis) from the Dutch LATER registry completed the Medical Outcome Study Short Form 36 (SF-36) to measure HRQOL and provided sociodemographic characteristics. Age-adjusted mean SF-36 scale scores of CCS were compared to the Dutch general population for men and women separately using t-tests, with effect size d. Multivariate logistic regression models were built to identify sociodemographic and cancer-related risk factors for impaired physical and mental HRQOL. RESULTS: Both male and female CCS (N = 2301, mean age = 35.4 years, 49.6% female) reported significantly (p ≤ .005) worse HRQOL than the general population on almost all scales of the SF-36 (-.11 ≤ d ≤ -.56). Largest differences were found on vitality and general health perceptions. Significant risk factors (p ≤ .05) for impaired physical HRQOL were female sex, older age at diagnosis, not having a partner, low educational attainment, disease recurrence and exposure to radiotherapy, specifically to lower extremity radiation. Odds ratios (ORs) ranged from 1.6 to 3.7. Significant risk factors for impaired mental HRQOL were age 26-35 years, male sex, not having a partner and low educational attainment. ORs ranged from 1.3 to 2.0. CONCLUSION: Adult CCS had worse HRQOL than the general population. CCS most at risk were those with low educational attainment and without a partner. Adult CCS could benefit from routine surveillance of their HRQOL. Special attention for CCS' vitality and health perceptions and beliefs is warranted.

20.
Cancer Genet ; 256-257: 127-130, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-34120093

RESUMEN

The BRCA1/2 gene is important for assessing the risk of familial/hereditary ovarian cancer (OC). This case is a patient with OC, and two of her immediate family members are cancer patients. We sequenced the coding and splicing regions of 42 OC susceptibility genes, and found a rare pathogenic splicing mutation BRCA1:c.132C > T (p.cys44 =) in 2 patients. Although the mutation is synonymous, software prediction and functional verification have shown that it affects alternative splicing and leads to frameshift mutations (c.131_134del). Chromosome microarray analysis of the tissue samples revealed the presence of a BRCA1 gene deletion with a fragment size of 1.42 Mb and an HRD score of 71. In addition, the proband showed a sensitive response to platinum treatment. This case suggests the clinical significance of OC susceptibility genes sequencing and HRD scoring in screening hereditary OC families.

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