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Military Medical Research Jan 2024Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens... (Review)
Review
Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO's report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship.
Topics: Humans; Artificial Intelligence; Anti-Bacterial Agents; Drug Resistance, Bacterial; Public Health
PubMed: 38254241
DOI: 10.1186/s40779-024-00510-1 -
Acta Neurochirurgica Oct 2023Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for...
BACKGROUND
Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally. Here we describe our institution's experience of patients presenting with metastatic meningiomas. We further perform a systematic review of the existing literature to explore common features of this rare manifestation of meningioma and review the efficacy of current treatments.
METHODS
We performed a retrospective clinical review of all adult patients with metastatic meningioma managed at our institution over the past 20 years, identifying 6 patients. We then performed a systematic review of cases of metastatic meningioma in the literature ranging from the years 1886 to 2022. A descriptive analysis was then conducted on the available data from 1979 onward, focusing on the grade and location of the primary tumor as well as the latency period to, and location of, the metastasis.
RESULTS
In total, we analyzed 155 cases. Fifty-four percent of patients initially presented with a primary meningioma located in the convexity. The most common site of metastasis was the lung. Risk factors associated with a shorter time to metastasis were male sex and a high initial grade of the tumor. Regarding treatment, the addition of chemotherapy was the most common adjunct to the standard management of surgery and radiotherapy. Despite an exhaustive review we were unable to identify effective treatments. The majority of published cases came from centers situated in high-income countries (84%) while only 16% came from lower- and middle-income countries.
CONCLUSIONS
Metastatic meningiomas pose a pertinent, and likely underestimated, clinical challenge within modern neurosurgery. To optimize management, timely identification of these patients is important. More research is needed to explore the mechanisms underlying these tumors to better guide the development of effective screening and management protocols. However, screening of each meningioma patient is not feasible, and at the heart of this challenge is the inability to control the primary disease. Ultimately, a consensus is needed as to how to correctly screen for and manage these patients; genomic and epigenomic approaches could hold the answer to finding druggable targets.
Topics: Adult; Female; Humans; Male; Brain Neoplasms; Meningeal Neoplasms; Meningioma; Retrospective Studies; Treatment Outcome
PubMed: 37491650
DOI: 10.1007/s00701-023-05687-3 -
Cancers Aug 2023High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6... (Review)
Review
High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0-5.5% for penile and 0-87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.
PubMed: 37627099
DOI: 10.3390/cancers15164068 -
Pharmacology & Therapeutics Jan 2024The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not... (Review)
Review
The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach.
Topics: Animals; Connective Tissue Growth Factor; Fibrosis; Fibroblasts; Transforming Growth Factor beta; Idiopathic Pulmonary Fibrosis; Transforming Growth Factor beta1; Lung
PubMed: 38103794
DOI: 10.1016/j.pharmthera.2023.108578 -
Cancers Sep 2023Bladder cancer (BC) diagnosis and prediction of prognosis are hindered by subjective pathological evaluation, which may cause misdiagnosis and under-/over-treatment.... (Review)
Review
Bladder cancer (BC) diagnosis and prediction of prognosis are hindered by subjective pathological evaluation, which may cause misdiagnosis and under-/over-treatment. Computational pathology (CPATH) can identify clinical outcome predictors, offering an objective approach to improve prognosis. However, a systematic review of CPATH in BC literature is lacking. Therefore, we present a comprehensive overview of studies that used CPATH in BC, analyzing 33 out of 2285 identified studies. Most studies analyzed regions of interest to distinguish normal versus tumor tissue and identify tumor grade/stage and tissue types (e.g., urothelium, stroma, and muscle). The cell's nuclear area, shape irregularity, and roundness were the most promising markers to predict recurrence and survival based on selected regions of interest, with >80% accuracy. CPATH identified molecular subtypes by detecting features, e.g., papillary structures, hyperchromatic, and pleomorphic nuclei. Combining clinicopathological and image-derived features improved recurrence and survival prediction. However, due to the lack of outcome interpretability and independent test datasets, robustness and clinical applicability could not be ensured. The current literature demonstrates that CPATH holds the potential to improve BC diagnosis and prediction of prognosis. However, more robust, interpretable, accurate models and larger datasets-representative of clinical scenarios-are needed to address artificial intelligence's reliability, robustness, and black box challenge.
PubMed: 37760487
DOI: 10.3390/cancers15184518 -
Insights Into Imaging Dec 2023Calcifications on mammography can be indicative of breast cancer, but the prognostic value of their appearance remains unclear. This systematic review and meta-analysis... (Review)
Review
BACKGROUND
Calcifications on mammography can be indicative of breast cancer, but the prognostic value of their appearance remains unclear. This systematic review and meta-analysis aimed to evaluate the association between mammographic calcification morphology descriptors (CMDs) and clinicopathological factors.
METHODS
A comprehensive literature search in Medline via Ovid, Embase.com, and Web of Science was conducted for articles published between 2000 and January 2022 that assessed the relationship between CMDs and clinicopathological factors, excluding case reports and review articles. The risk of bias and overall quality of evidence were evaluated using the QUIPS tool and GRADE. A random-effects model was used to synthesize the extracted data. This systematic review is reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
RESULTS
Among the 4715 articles reviewed, 29 met the inclusion criteria, reporting on 17 different clinicopathological factors in relation to CMDs. Heterogeneity between studies was present and the overall risk of bias was high, primarily due to small, inadequately described study populations. Meta-analysis demonstrated significant associations between fine linear calcifications and high-grade DCIS [pooled odds ratio (pOR), 4.92; 95% confidence interval (CI), 2.64-9.17], (comedo)necrosis (pOR, 3.46; 95% CI, 1.29-9.30), (micro)invasion (pOR, 1.53; 95% CI, 1.03-2.27), and a negative association with estrogen receptor positivity (pOR, 0.33; 95% CI, 0.12-0.89).
CONCLUSIONS
CMDs detected on mammography have prognostic value, but there is a high level of bias and variability between current studies. In order for CMDs to achieve clinical utility, standardization in reporting of CMDs is necessary.
CRITICAL RELEVANCE STATEMENT
Mammographic calcification morphology descriptors (CMDs) have prognostic value, but in order for CMDs to achieve clinical utility, standardization in reporting of CMDs is necessary.
SYSTEMATIC REVIEW REGISTRATION
CRD42022341599 KEY POINTS: • Mammographic calcifications can be indicative of breast cancer. • The prognostic value of mammographic calcifications is still unclear. • Specific mammographic calcification morphologies are related to lesion aggressiveness. • Variability between studies necessitates standardization in calcification evaluation to achieve clinical utility.
PubMed: 38051355
DOI: 10.1186/s13244-023-01529-z -
Reviews in Medical Virology Sep 2023Head and neck cancer, one of the most commonly prevalent malignancies globally is a complex category of tumours that comprises cancers of the oral cavity, pharynx, and... (Review)
Review
A systematic review on the molecular and clinical association between Human Papillomavirus and Human Immunodeficiency Virus co-infection in Head, Neck and Oral squamous cell carcinoma.
Head and neck cancer, one of the most commonly prevalent malignancies globally is a complex category of tumours that comprises cancers of the oral cavity, pharynx, and larynx. A specific subgroup of such cancers has been found with some unique chromosomal, therapeutic, and epidemiologic traits with the possibility of affecting via co-infection. About 25% of all head and neck cancers in the population are human papillomavirus infection (HPV)-associated, typically developing in the oropharynx, which comprises the tonsils. In the period of efficient combined antiviral treatment, HPV-positive oral cancers are also becoming a significant contributor to illness and fatality for Human Immunodeficiency Virus (HIV)-infected persons. Although the prevalence and historical background of oral HPV transmission are not thoroughly understood, it seems likely that oral HPV transmission is relatively frequent in HIV-infected people when compared to the overall population. Therefore, there is a need to understand the mechanisms leading to this co-infection, as there is very little research related to that. Hence, this study mainly focus on the therapeutical and biomedical analysis of HPV and HIV co-infection in the above-mentioned cancer, including oral squamous cell carcinoma.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Mouth Neoplasms; Human Papillomavirus Viruses; Papillomavirus Infections; Coinfection; Head and Neck Neoplasms; HIV Infections; HIV; Papillomaviridae
PubMed: 37280764
DOI: 10.1002/rmv.2462 -
Journal of Translational Medicine Oct 2023Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models-each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types.
METHODS
We searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies.
RESULTS
We included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92-96) for orthotopic and 95% (93-96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33-72) and heterotopic 82% (73-89)] and finally GEM revealed a TTR of 34% (26-43).
CONCLUSION
This systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages).
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42022308833.
Topics: Animals; Humans; Meningeal Neoplasms; Meningioma; Reproducibility of Results; Disease Models, Animal
PubMed: 37898750
DOI: 10.1186/s12967-023-04620-7 -
European Journal of Nuclear Medicine... Sep 2023Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, Tc-tilmanocept is of particular interest due to its low molecular weight... (Meta-Analysis)
Meta-Analysis
Tc-Tilmanocept performance for sentinel node mapping in breast cancer, melanoma, and head and neck cancer: a systematic review and meta-analysis from a European expert panel.
PURPOSE
Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, Tc-tilmanocept is of particular interest due to its low molecular weight and specific binding capability for the mannose receptors of lymphatic reticuloendothelial cells. In the current systematic review and meta-analysis, we aimed to provide an update from a European expert panel on the performance of Tc-tilmanocept for SN biopsy.
METHODS
A systematic literature search of the PubMed/Medline and Embase databases was performed to identify studies on the use of Tc-tilmanocept for SN identification in oncological patients. The articles' methodological quality was assessed before inclusion. The pooled estimates of the pre-/intraoperative detection rates (DR; proportion of patients with ≥ 1 SN identified) and/or pN + sensitivity (SN + /pN + patients ratio), with 95% confidence intervals (CIs), were calculated for breast cancer, melanoma, and head and neck cancer.
RESULTS
Twenty-four articles were included in the systematic review, and twenty-one provided data for the meta-analysis. According to data availability, the Tc-tilmanocept-estimated pooled preoperative and intraoperative DRs were 0.94 (95%CI, 0.88-1.01) and 0.99 (0.98-1.00) for breast cancer, 0.98 (0.96-0.99) and 1.00 (0.99-1.00) for melanoma, and 0.97 (0.93-1.02) and 0.99 (0.96-1.01) for head and neck carcinoma. Finally, the pooled sensitivity for nodal metastasis in melanoma was 0.97 (95% CI, 0.92-1.03).
CONCLUSION
Tc-tilmanocept is a promising radiotracer for SN mapping in patients with breast cancer, melanoma, or head and neck cancer. We strongly believe that multicenter trials are still needed to assess if Tc-tilmanocept is superior to other radiotracers used in clinical routine.
Topics: Humans; Female; Breast Neoplasms; Lymphatic Metastasis; Radiopharmaceuticals; Sentinel Lymph Node Biopsy; Melanoma; Head and Neck Neoplasms; Lymph Nodes
PubMed: 37310426
DOI: 10.1007/s00259-023-06290-5 -
The Lancet. Diabetes & Endocrinology Aug 2023Enteroviruses are routinely detected with molecular methods within large cohorts that are at risk of type 1 diabetes. We aimed to examine the association between... (Meta-Analysis)
Meta-Analysis
Enteroviruses and risk of islet autoimmunity or type 1 diabetes: systematic review and meta-analysis of controlled observational studies detecting viral nucleic acids and proteins.
BACKGROUND
Enteroviruses are routinely detected with molecular methods within large cohorts that are at risk of type 1 diabetes. We aimed to examine the association between enteroviruses and either islet autoimmunity or type 1 diabetes.
METHODS
For this systematic review and meta-analysis, we searched PubMed and Embase for controlled observational studies from inception until Jan 1, 2023. Cohort or case-control studies were eligible if enterovirus RNA or protein were detected in individuals with outcomes of islet autoimmunity or type 1 diabetes. Studies in pregnancy or other types of diabetes were excluded. Data extraction and appraisal involved author contact and deduplication, which was done independently by three reviewers. Study quality was assessed with the Newcastle-Ottawa Scale and National Health and Medical Research Council levels of evidence. Pooled and subgroup meta-analyses were done in RevMan version 5.4, with random effects models and Mantel-Haenszel odds ratios (ORs; 95% CIs). The study is registered with PROSPERO, CRD42021278863.
FINDINGS
The search returned 3266 publications, with 897 full texts screened. Following deduplication, 113 eligible records corresponded to 60 studies (40 type 1 diabetes; nine islet autoimmunity; 11 both), comprising 12077 participants (5981 cases; 6096 controls). Study design and quality varied, generating substantial statistical heterogeneity. Meta-analysis of 56 studies showed associations between enteroviruses and islet autoimmunity (OR 2·1, 95% CI 1·3-3·3; p=0·002; n=18; heterogeneity χ/df 2·69; p=0·0004; I=63%), type 1 diabetes (OR 8·0, 95% CI 4·9-13·0; p<0·0001; n=48; χ/df 6·75; p<0·0001; I=85%), or within 1 month of type 1 diabetes (OR 16·2, 95% CI 8·6-30·5; p<0·0001; n=28; χ/df 3·25; p<0·0001; I=69%). Detection of either multiple or consecutive enteroviruses was associated with islet autoimmunity (OR 2·0, 95% CI 1·0-4·0; p=0·050; n=8). Detection of Enterovirus B was associated with type 1 diabetes (OR 12·7, 95% CI 4·1-39·1; p<0·0001; n=15).
INTERPRETATION
These findings highlight the association between enteroviruses and islet autoimmunity or type 1 diabetes. Our data strengthen the rationale for vaccine development targeting diabetogenic enterovirus types, particularly those within Enterovirus B. Prospective studies of early life are needed to elucidate the role of enterovirus timing, type, and infection duration on the initiation of islet autoimmunity and the progression to type 1 diabetes.
FUNDING
Environmental Determinants of Islet Autoimmunity, European Association for the Study of Diabetes, JDRF, Australian National Health and Medical Research Council, and University of New South Wales.
Topics: Pregnancy; Female; Humans; Diabetes Mellitus, Type 1; Autoimmunity; Prospective Studies; Nucleic Acids; Australia; Enterovirus; Observational Studies as Topic
PubMed: 37390839
DOI: 10.1016/S2213-8587(23)00122-5