Oral mucositis: the hidden side of cancer therapy Pulito, Claudio; Cristaudo, Antonio; Porta, Caterina La ...
Journal of experimental & clinical cancer research,
10/2020, Volume:
39, Issue:
1
Journal Article
Peer reviewed
Open access
Inflammation response of epithelial mucosa to chemo- radiotherapy cytotoxic effects leads to mucositis, a painful side effect of antineoplastic treatments. About 40% of the patients treated with ...chemotherapy develop mucositis; this percentage rises to about 90% for head and neck cancer patients (HNC) treated with both chemo- and radiotherapy. 19% of the latter will be hospitalized and will experience a delay in antineoplastic treatment for high-grade mucositis management, resulting in a reduction of the quality of life, a worse prognosis and an increase in patient management costs. Currently, several interventions and prevention guidelines are available, but their effectiveness is uncertain. This review comprehensively describes mucositis, debating the impact of standard chemo-radiotherapy and targeted therapy on mucositis development and pointing out the limits and the benefits of current mucositis treatment strategies and assessment guidelines. Moreover, the review critically examines the feasibility of the existing biomarkers to predict patient risk of developing oral mucositis and their role in early diagnosis. Despite the expression levels of some proteins involved in the inflammation response, such as TNF-alpha or IL-1beta, partially correlate with mucositis process, their presence does not exclude others mucositis-independent inflammation events. This strongly suggests the need to discover biomarkers that specifically feature mucositis process development. Non-coding RNAs might hold this potential. Keywords: Oral mucositis, HNC, Biomarker, Cytokine, Non-coding RNA, Quality of life
•Asymptomatic COVID-19 cases represent the most common mean of contagion.•Asymptomatic COVID-19 cases may have the same infectivity as symptomatic infections.•Spread of COVID-19 in homeless shelters ...represents a serious public health threat.•Homeless persons are subject to more severe forms of COVID-19.•Prevention measures should be implemented in all homeless shelters.
Asymptomatic carriers account for over a third of all Coronavirus Disease 19 (COVID-19) cases and are characterized by the absence of symptoms but the same infectivity as symptomatic infections. The high percentage of asymptomatic COVID-19 patients is significant in settings with specific vulnerabilities, such as homeless shelters, where the consequences of an outbreak may be dramatic. In this work, we briefly report our experience on residents and staff of homeless shelters in the City of Rome, Italy, with a particular focus on asymptomatic transmission, and compare it with the available evidence.
We performed routine Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nasopharyngeal swab tests in all residents and staff of homeless shelters managed by the Eleemosynaria Apostolica of the Vatican City State in the city of Rome, Italy, in addition to daily symptom screening, body temperature monitoring, and application of other prevention measures.
We evaluated 298 persons and identified twelve positive cases (4%). Most of the positive cases (75%) were asymptomatic, while only three patients reported symptoms that included fever, diarrhea, and cough.
Our data confirm the importance of early identification of asymptomatic carriers that could, in vulnerable conditions such as homeless shelters, spread the infection and cause outbreaks with severe consequences on individual and public health.
Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative ...malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose.
Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher' exact test and the Mann-Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively.
At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM (p = 0.003) and 172.9 in MPM patients (p = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM (p = 0.003) and 88% in MPM patients (p = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed (p = 0.913), while there was a significant trend toward lower titers by increasing age (p < 0.001) and in disease cohorts with respect to controls (MM: p < 0.001 and MPM: p < 0.001). An ongoing treatment without daratumumab was associated with higher likelihood of response in MM patients (p = 0.003). No swabs resulted positive on each time point. No safety concerns were observed.
BNT162b2 has demonstrated to be immunogenic at different extent among the cohorts. Response was 88% and robust in MPM patients. MM patients responded significantly less, particularly those on anti-CD38-based treatment. These latter patients should be advised to maintain masks and social distancing regardless of vaccination status, and their cohabiting family members need to be vaccinated in order to reduce the risk of contagion from the family. Additional boosters and titer monitoring could be considered. Trial registration Study was formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21).
Skin pigmentation is the most variable human characteristic that can be observed and has been used throughout history to classify humans into distinct groups. Many factors influence skin colour, but ...the melanin pigment is considered the most important because its type and quantity can determine variations in pigmentation shades. The evolution of skin pigmentation started around 1.6-2 million years ago. As a result of migratory phenomena to places with less ultraviolet radiation (UVR) and other seasonal regimes, the selection of depigmented skin and different tanning capabilities occurred over time. Thus, genetic adaptation to new environmental conditions gradually led to changes in skin pigmentation. Despite the biological importance of pigmentation, variation in skin colour has led to social and health inequalities. Since Linnaeus, skin colour classifications have been used to describe different human groups, encouraging the misuse of a biological characteristic. This review examines the characterisation of pigmentation and its evolution through history and society. The unequal perception of pigmentation diversity has led to an incomplete state of dermatological training and issues in medical approach in dermatology. The consciousness of all these aspects increases the need to address and overcome dermatologic and social health disparities related to skin pigmentation.
Acne vulgaris is a common inflammatory disorder affecting more than 80% of young adolescents. Cutibacterium acnes plays a role in the pathogenesis of acne lesions, although the mechanisms are poorly ...understood. The study aimed to explore the microbiome at different skin sites in adolescent acne and the role of biofilm production in promoting the growth and persistence of C. acnes isolates. Microbiota analysis showed a significantly lower alpha diversity in inflammatory lesions (LA) than in non-inflammatory (NI) lesions of acne patients and healthy subjects (HS). Differences at the species level were driven by the overabundance of C. acnes on LA than NI and HS. The phylotype IA1 was more represented in the skin of acne patients than in HS. Genes involved in lipids transport and metabolism, as well as potential virulence factors associated with host-tissue colonization, were detected in all IA1 strains independently from the site of isolation. Additionally, the IA1 isolates were more efficient in early adhesion and biomass production than other phylotypes showing a significant increase in antibiotic tolerance. Overall, our data indicate that the site-specific dysbiosis in LA and colonization by virulent and highly tolerant C. acnes phylotypes may contribute to acne development in a part of the population, despite the universal carriage of the microorganism. Moreover, new antimicrobial agents, specifically targeting biofilm-forming C. acnes, may represent potential treatments to modulate the skin microbiota in acne.
SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 ...expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas.
The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC.
TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation.
Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.
The treatment and management of patients with metastatic melanoma have evolved considerably in the "era" of personalized medicine. Melanoma was one of the first solid tumors to benefit from ...immunotherapy; life expectancy for patients in advanced stage of disease has improved. However, many progresses have yet to be made considering the (still) high number of patients who do not respond to therapies or who suffer adverse events. In this scenario, precision medicine appears fundamental to direct the most appropriate treatment to the single patient and to guide towards treatment decisions. The recent multi-omics analyses (genomics, transcriptomics, proteomics, metabolomics, radiomics, etc.) and the technological evolution of data interpretation have allowed to identify and understand several processes underlying the biology of cancer; therefore, improving the tumor clinical management. Specifically, these approaches have identified new pharmacological targets and potential biomarkers used to predict the response or adverse events to treatments. In this review, we will analyze and describe the most important omics approaches, by evaluating the methodological aspects and progress in melanoma precision medicine.
Objectives:
To furnish a model to ensure access and use of healthcare services to the undocumented and homeless population.
Methods:
Between March 2020 and October 2021, public and third sector ...actors in Rome implemented an accessible COVID-19 screening service and vaccination program targeting the homeless and undocumented population.
Results:
95.6% of the patients tested negative to both rapid and molecular tests. 0.9% tested positive to both. 0.7% were false negatives, while 2.8% were false positives. None of the participants refused the diagnostic treatment. From July to October 2021, 1384 people received a complete cycle of the COVID-19 vaccine through the program. 632 (45.6%) also agreed to perform the antibodies testing before inoculation. 318 (50.31%) of these were positive at the time of vaccination.
Conclusion:
We present a cost-effective model for reducing structural barriers to access diagnostic and preventive services for the homeless and undocumented population that can be applied to different public health settings.
Intermittent circadian fasting, namely Ramadan, is a common worldwide practice. Such fasting has a positive impact on psoriasis, but no data exist on its role in psoriatic arthritis (PsA)-a disease ...that is clearly linked to body mass index. We enrolled 37 patients (23 females and 14 males) with a mean age 43.32 ± 7.81 and they fasted for 17 h for one month in 2016. The baseline PsA characteristics were collected and 12 (32.4%) patients had peripheral arthritis, 13 (35.1%) had axial involvement, 24 (64.9%) had enthesitis, and 13 (35.1%) had dactylitis. Three patients (8.1%) were treated with methotrexate, 28 (75.7%) with TNF-α blockers, and 6 (16.2%) with IL-17 blockers. After a month of intermittent fasting, C-reactive protein (CRP) levels decreased from 14.08 ± 4.65 to 12.16 ± 4.46 (
< 0.0001), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 2.83 ± 1.03 to 2.08 ± 0.67 (
= 0.0078), Psoriasis Area Severity Index (PASI) decreased from 7.46 ± 2.43 to 5.86 ± 2.37 (
< 0.0001), and Disease Activity index for PSoriatic Arthritis (DAPSA) decreased from 28.11 ± 4.51 to 25.76 ± 4.48 (
< 0.0001). Similarly, enthesitis improved after fasting, with Leeds Enthesitis Index (LEI) decreasing from 2.25 ± 1.11 to 1.71 ± 0.86 (
< 0.0001) and dactylitis severity score (DSS) decreasing from 9.92 ± 2.93 to 8.54 ± 2.79 (
= 0.0001). Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting. These preliminary data may support the use of chronomedicine in the context of rheumatic diseases, namely PsA. Further studies are needed to support our findings.
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