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International Journal of Molecular... May 2024Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel and uncommon type of renal cell carcinoma, which has been recently recognized and introduced as a... (Meta-Analysis)
Meta-Analysis
Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel and uncommon type of renal cell carcinoma, which has been recently recognized and introduced as a distinct entity in the WHO 2022 kidney tumor classification. Previously known as "unclassified RCC", followed by "tuberous sclerosis complex (TSC)-associated RCC", ESC-RCC is now a distinct category of kidney tumor, with its own name, with specific clinical manifestations, and a unique morphological, immunohistochemical and molecular profile. Due to its recent introduction and the limited available data, the diagnosis of ESC-RCC is still a complex challenge, and it is probably frequently misdiagnosed. The secret of diagnosing this tumor lies in the pathologists' knowledge, and keeping it up to date through research, thereby limiting the use of outdated nomenclature. The aim of our case-based review is to provide a better understanding of this pathology and to enrich the literature with a new case report, which has some particularities compared to the existing cases.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Eosinophilia; Male
PubMed: 38892169
DOI: 10.3390/ijms25115982 -
Mayo Clinic Proceedings. Innovations,... Oct 2023To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19.
OBJECTIVE
To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19.
PATIENTS AND METHODS
On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization.
RESULTS
Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82).
CONCLUSION
During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.
PubMed: 37859995
DOI: 10.1016/j.mayocpiqo.2023.09.001 -
Healthcare (Basel, Switzerland) Sep 2023Cancer is a leading cause of mortality and morbidity all over the world and the second major cause of death in Portugal. Dermatological side effects resulting from... (Review)
Review
Cancer is a leading cause of mortality and morbidity all over the world and the second major cause of death in Portugal. Dermatological side effects resulting from cancer treatment have a psychosocial impact on patients' lives, such as quality of life (QoL), body image, cognitive fusion and social inhibition. This systematic review aimed to explore and synthesize the psychosocial impact of dermatological side effects of cancer treatment, answering the following research objectives: (i) Do the dermatological side effects of the cancer treatment present any psychosocial impact for the patients? (ii) How does the psychosocial impact of the dermatological toxicities of the cancer treatment manifest in patients' lives? Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and guided a systematic search through the PubMed, Cochrane Library and PyscNet databases. The considered studies correlate dermatological side effects of cancer treatments and their psychological/psychosocial outcomes. The studies found were all published in peer-reviewed journals. The results obtained established that cancer treatment causes the most varied skin changes, consequently reducing self-esteem and QoL; disturbing body image; and contributing to cases of stress, depression and anxiety. There is still limited literature that profoundly investigates the experience of living with these skin toxicities. The development of research lines to improve knowledge in this field will allow for significant improvements in healthcare for patients undergoing cancer treatment who need to focus more on the psychosocial implications of skin toxicities. The novelty of this review lies in adding knowledge summarizing the psychosocial implications of dermatological side effects of cancer treatment to support healthcare providers in the development of integrative therapeutic strategies for these patients in their clinical practice.
PubMed: 37830658
DOI: 10.3390/healthcare11192621 -
Journal of Translational Medicine Aug 2023Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate...
BACKGROUND
Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate a Robust Prognostic Model for IDH wild-type GBM (COVPRIG) for the prediction of overall survival using a novel metric, gene-gene (G × G) interaction, and explore molecular and cellular underpinnings.
METHODS
Univariate and multivariate Cox regression of four independent trans-ethnic cohorts containing a total of 800 samples. Prediction efficacy was comprehensively evaluated and compared with previous models by a systematic literature review. The molecular underpinnings of COVPRIG were elucidated by integrated analysis of bulk-tumor and single-cell based datasets.
RESULTS
Using a Cox-ph model-based method, six of the 93,961 G × G interactions were screened to form an optimal combination which, together with age, comprised the COVPRIG model. COVPRIG was designed for RNA-seq and microarray, respectively, and effectively identified patients at high risk of mortality. The predictive performance of COVPRIG was satisfactory, with area under the curve (AUC) ranging from 0.56 (CGGA693, RNA-seq, 6-month survival) to 0.79 (TCGA RNAseq, 18-month survival), which can be further validated by decision curves. Nomograms were constructed for individual risk prediction for RNA-seq and microarray-based cohorts, respectively. Besides, the prognostic significance of COVPRIG was also validated in GBM including the IDH mutant samples. Notably, COVPRIG was comprehensively evaluated and externally validated, and a systemic review disclosed that COVPRIG outperformed current validated models with an integrated discrimination improvement (IDI) of 6-16%. Moreover, integrative bioinformatics analysis predicted an essential role of METTL1 neural-progenitor-like (NPC-like) malignant cell in driving unfavorable outcome.
CONCLUSION
This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.
Topics: Humans; Glioblastoma; Isocitrate Dehydrogenase; Brain Neoplasms; Prognosis; Nomograms; Methyltransferases
PubMed: 37553713
DOI: 10.1186/s12967-023-04382-2 -
International Journal of Molecular... Feb 2024Standard non-melanoma skin cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in cases of advanced tumors. EVs, including... (Review)
Review
Standard non-melanoma skin cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in cases of advanced tumors. EVs, including exosomes, are integral to carcinogenesis, and are found in NMSC releasing mediators impacting tumor progression. Nevertheless, the precise intercellular signaling role of NMSC-derived EVs remains unclear. This review aims to elucidate their potential role in NMSC diagnosis and treatment. This systematic review encompassed literature searches in electronic databases from inception to September 2023, based on certain inclusion and exclusion criteria, addressing NMSC-derived EVs, their molecular cargo, and their implications in the diagnosis, prognosis, and treatment of NMSC. Key components were identified. Extracellular vesicle (EV) proteins and RNA have emerged as diagnostic biomarkers in EV-based liquid biopsy. Circular RNA CYP24A1, known for its molecular stability, holds promise as a diagnostic biomarker. Long noncoding RNAs (lincRNA-PICSAR) and Desmoglein 2 (DSg2) are linked to drug resistance, serving as prognostic biomarkers. EV mediators are being actively investigated for their potential role as drug delivery agents. In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend EV mechanisms and explore their potential in cancer diagnosis and treatment.
Topics: Humans; Extracellular Vesicles; Exosomes; Liquid Biopsy; Skin Neoplasms; Biomarkers
PubMed: 38473864
DOI: 10.3390/ijms25052617 -
The Lancet. Global Health Jan 2024Tuberculosis is a leading cause of infectious disease mortality worldwide, but diagnosis of pulmonary tuberculosis remains challenging. Oral swabs are a promising...
BACKGROUND
Tuberculosis is a leading cause of infectious disease mortality worldwide, but diagnosis of pulmonary tuberculosis remains challenging. Oral swabs are a promising non-sputum alternative sample type for the diagnosis of pulmonary tuberculosis. We aimed to assess the diagnostic accuracy of oral swabs to detect pulmonary tuberculosis in adults and children and suggest research implications.
METHODS
In this systematic review, we searched published and preprint studies from Jan 1, 2000, to July 5, 2022, from eight databases (MEDLINE, Embase, Scopus, Science Citation Index, medRxiv, bioRxiv, Global Index Medicus, and Google Scholar). We included diagnostic accuracy studies including cross-sectional, cohort, and case-control studies in adults and children from which we could extract or derive sensitivity and specificity of oral swabs as a sample type for the diagnosis of pulmonary tuberculosis against a sputum microbiological (nucleic acid amplification test [NAAT] on sputum or culture) or composite reference standard.
FINDINGS
Of 550 reports identified by the search, we included 16 eligible reports (including 20 studies and 3083 participants) that reported diagnostic accuracy estimates on oral swabs for pulmonary tuberculosis. Sensitivity on oral swabs ranged from 36% (95% CI 26-48) to 91% (80-98) in adults and 5% (1-14) to 42% (23-63) in children. Across all studies, specificity ranged from 66% (95% CI 52-78) to 100% (97-100), with most studies reporting specificity of more than 90%. Meta-analysis was not performed because of sampling and testing heterogeneity.
INTERPRETATION
Sensitivity varies in both adults and children when diverse methods are used. Variability in sampling location, swab type, and type of NAAT used in accuracy studies limits comparison. Although data are suggestive that high accuracy is achievable using oral swabs with molecular testing, more research is needed to define optimal methods for using oral swabs as a specimen for tuberculosis detection. The current data suggest that tongue swabs and swab types that collect increased biomass might have increased sensitivity. We would recommend that future studies use these established methods to continue to refine sample processing to maximise sensitivity.
FUNDING
Bill and Melinda Gates foundation (INV-045721) and FIND (Netherlands Enterprise Agency on behalf of the Minister for Foreign Trade and Development Cooperation [NL-GRNT05] and KfW Development Bank, German Federal Ministry of Education and Research [KFW-TBBU01/02]).
Topics: Adult; Child; Humans; Mycobacterium tuberculosis; Cross-Sectional Studies; Pathology, Molecular; Tuberculosis, Pulmonary; Tuberculosis; Sensitivity and Specificity; Molecular Diagnostic Techniques
PubMed: 38097297
DOI: 10.1016/S2214-109X(23)00469-2 -
European Urology Jan 2024In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand...
BACKGROUND
In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.
OBJECTIVE
We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.
DESIGN, SETTING, AND PARTICIPANTS
The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.
RESULTS AND LIMITATIONS
After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [Ra]RaCl remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both []FDG and PSMA PET prior to [Lu]Lu-PSMA therapy.
CONCLUSIONS
There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.
PATIENT SUMMARY
There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.
Topics: Humans; Male; Molecular Imaging; Nuclear Medicine; Positron-Emission Tomography; Precision Medicine; Prostatic Neoplasms
PubMed: 37743194
DOI: 10.1016/j.eururo.2023.09.003 -
Diagnostics (Basel, Switzerland) Dec 2023Mismatch repair deficiency (d-MMR)/microsatellite instability (MSI), , and mutational status are crucial for treating advanced colorectal cancer patients. Traditional... (Review)
Review
Mismatch repair deficiency (d-MMR)/microsatellite instability (MSI), , and mutational status are crucial for treating advanced colorectal cancer patients. Traditional methods like immunohistochemistry or polymerase chain reaction (PCR) can be challenged by artificial intelligence (AI) based on whole slide images (WSI) to predict tumor status. In this systematic review, we evaluated the role of AI in predicting MSI status, , and mutations in colorectal cancer. Studies published in PubMed up to June 2023 were included ( = 17), and we reported the risk of bias and the performance for each study. Some studies were impacted by the reduced number of slides included in the data set and the lack of external validation cohorts. Deep learning models for the d-MMR/MSI status showed a good performance in training cohorts (mean AUC = 0.89, [0.74-0.97]) but slightly less than expected in the validation cohort when available (mean AUC = 0.82, [0.63-0.98]). Contrary to the MSI status, the prediction of and mutations was less explored with a less robust methodology. The performance was lower, with a maximum of 0.77 in the training cohort, 0.58 in the validation cohort for , and 0.82 AUC in the training cohort for .
PubMed: 38201408
DOI: 10.3390/diagnostics14010099 -
Journal of Immunotherapy (Hagerstown,... May 2024The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the...
Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET , or RET Alterations: A Systematic Literature Review.
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Proto-Oncogene Proteins B-raf; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins c-ret; Receptor, ErbB-2
PubMed: 38112201
DOI: 10.1097/CJI.0000000000000500 -
Biology Feb 2024Oral squamous cell carcinoma (OSCC) is the most common and lethal type of head and neck cancer in the world. Variable response and acquisition of resistance to... (Review)
Review
Oral squamous cell carcinoma (OSCC) is the most common and lethal type of head and neck cancer in the world. Variable response and acquisition of resistance to traditional therapies show that it is essential to develop novel strategies that can provide better outcomes for the patient. Understanding of cellular and molecular mechanisms of cell death control has increased rapidly in recent years. Activation of cell death pathways, such as the emerging forms of non-apoptotic programmed cell death, including ferroptosis, pyroptosis, necroptosis, NETosis, parthanatos, mitoptosis and paraptosis, may represent clinically relevant novel therapeutic opportunities. This systematic review summarizes the recently described forms of cell death in OSCC, highlighting their potential for informing diagnosis, prognosis and treatment. Original studies that explored any of the selected cell deaths in OSCC were included. Electronic search, study selection, data collection and risk of bias assessment tools were realized. The literature search was carried out in four databases, and the extracted data from 79 articles were categorized and grouped by type of cell death. Ferroptosis, pyroptosis, and necroptosis represented the main forms of cell death in the selected studies, with links to cancer immunity and inflammatory responses, progression and prognosis of OSCC. Harnessing the potential of these pathways may be useful in patient-specific prognosis and individualized therapy. We provide perspectives on how these different cell death types can be integrated to develop decision tools for diagnosis, prognosis, and treatment of OSCC.
PubMed: 38392321
DOI: 10.3390/biology13020103