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Molecular Diagnosis & Therapy Jul 2024HtrA1, HtrA2, HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search...
PURPOSE
HtrA1, HtrA2, HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search performed to compare the expression of HtrA family genes and proteins in cancer versus non-cancer tissues and cell lines, assess relationships between HtrA expression and cancer clinical features in cancer, and analyse the molecular mechanism, by which HtrA family affects cancer.
METHODS
The literature search was conducted according to the PRISMA statement among four databases (PubMed, Web of Science, Embase and Scopus).
RESULTS
A total of 38 articles met the inclusion criteria and involved the expression of HtrA family members and concerned the effect of HtrA expression on cancer and metastasis development or on the factor that influences it. Additionally, 31 reports were retrieved manually. Most articles highlighted that HtrA1 and HtrA3 exhibited tumour suppressor activity, while HtrA2 was associated with tumour growth and metastasis. There were too few studies to clearly define the role of the HtrA4 protease in tumours.
CONCLUSION
Although the expression of serine proteases of the HtrA family was dependent on tumour type, stage and the presence of metastases, most articles indicated that HtrA1 and HtrA3 expression in tumours was downregulated compared with healthy tissue or cell lines. The expression of HtrA2 was completely study dependent. The limited number of studies on HtrA4 expression made it impossible to draw conclusions about differences in expression between healthy and tumour tissue. The conclusions drawn from the study suggest that HtrA1 and HtrA3 act as tumour suppressors.
Topics: Humans; Neoplasms; High-Temperature Requirement A Serine Peptidase 1; Serine Endopeptidases; High-Temperature Requirement A Serine Peptidase 2; Gene Expression Regulation, Neoplastic; Mitochondrial Proteins
PubMed: 38717523
DOI: 10.1007/s40291-024-00712-2 -
JAC-antimicrobial Resistance Jun 2024The cefazolin inoculum effect (CzIE) is a phenomenon whereby some MSSA isolates demonstrate resistance to cefazolin when a high bacterial inoculum is used for... (Review)
Review
BACKGROUND
The cefazolin inoculum effect (CzIE) is a phenomenon whereby some MSSA isolates demonstrate resistance to cefazolin when a high bacterial inoculum is used for susceptibility testing. The clinical significance of this phenotypic phenomenon remains unclear. We conducted a systematic review to answer the following question: In patients with serious MSSA infection treated with cefazolin, does infection due to CzIE-positive MSSA isolates result in worse clinical outcomes than infection due to CzIE-negative MSSA isolates?
METHODS
Ovid MEDLINE, Embase, Cochrane CENTRAL, medRxiv and bioRxiv were searched from inception until 12 April 2023. Studies were included if they tested for CzIE in clinical isolates from MSSA infections in humans. Two independent reviewers extracted data and conducted risk-of-bias assessment. Main outcomes were treatment failure and mortality. Pooling of study estimates was not performed given the heterogeneity of patient populations and outcome definitions.
RESULTS
Twenty-three observational studies were included. CzIE presence amidst MSSA isolates ranged from 0% to 55%. There was no statistically significant mortality difference in two studies that compared MSSA infections with and without CzIE, with ORs ranging from 0.72 to 19.78. Of four studies comparing treatment failure, ORs ranged from 0.26 to 13.00. One study showed a significantly higher treatment failure for the CzIE group, but it did not adjust for potential confounders.
CONCLUSIONS
The evidence on CzIE is limited by small observational studies. In these studies, CzIE did not predict higher mortality in MSSA infections treated with cefazolin. Our findings do not support CzIE testing in clinical practice currently.
PubMed: 38716403
DOI: 10.1093/jacamr/dlae069 -
BMC Public Health May 2024A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV) prefusion F vaccine.
METHODS
We conducted a comprehensive search across PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to retrieve articles related to the efficacy, immunogenicity, and safety of RSV prefusion F vaccines, published through September 8, 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 22 randomized controlled trials involving 78,990 participants were included in this systematic review and meta-analysis. The RSV prefusion F vaccine exhibited a vaccine effectiveness of 68% (95% CI: 59-75%) against RSV-associated acute respiratory illness, 70% (95% CI: 60-77%) against medically attended RSV-associated lower respiratory tract illness, and 87% (95% CI: 71-94%) against medically attended severe RSV-associated lower respiratory tract illness. Common reported local adverse reactions following RSV prefusion F vaccination include pain, redness, and swelling at the injection site, and systemic reactions such as fatigue, headache, myalgia, arthralgia, nausea, and chills.
CONCLUSIONS
Our meta-analysis suggests that vaccines using the RSV prefusion F protein as antigen exhibit appears broadly acceptable efficacy, immunogenicity, and safety in the population. In particular, it provides high protective efficiency against severe RSV-associated lower respiratory tract disease.
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Vaccine Efficacy; Respiratory Syncytial Virus, Human; Immunogenicity, Vaccine; Randomized Controlled Trials as Topic
PubMed: 38711074
DOI: 10.1186/s12889-024-18748-8 -
Wiley Interdisciplinary Reviews. RNA 2024Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is... (Review)
Review
Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is derived from chromosome 2p11.2. Many studies prove that LINC00152 influences the progression of various tumors via promoting the tumor cells malignant phenotype, chemoresistance, and immune escape. LINC00152 is regulated by multiple transcription factors and DNA hypomethylation. In addition, LINC00152 participates in the regulation of complex molecular signaling networks through epigenetic regulation, protein interactions, and competitive endogenous RNA (ceRNA). Here, we provide a systematic review of the upstream regulatory factors of LINC00152 expression level in different types of tumors. In addition, we revisit the main functions and mechanisms of LINC00152 as driver oncogene and biomarker in pan-cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
Topics: RNA, Long Noncoding; Humans; Neoplasms; Oncogenes; Gene Expression Regulation, Neoplastic
PubMed: 38702938
DOI: 10.1002/wrna.1851 -
Diseases of the Colon and Rectum Jun 2024A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to...
BACKGROUND
A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment.
OBJECTIVE
The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy.
DESIGN
A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI).
SETTING
The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online.
MAIN OUTCOME MEASURES
The main outcome was to reach consensus (80% or more agreement).
RESULTS
The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response.
LIMITATIONS
This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice.
CONCLUSIONS
Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract.
UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO
ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).
Topics: Humans; Rectal Neoplasms; Neoadjuvant Therapy; Delphi Technique; Consensus; Chemoradiotherapy; Treatment Outcome; Diffusion Magnetic Resonance Imaging
PubMed: 38701503
DOI: 10.1097/DCR.0000000000003209 -
Advances in Anatomic Pathology Jul 2024This is the first systematic review and meta-analysis of The International System (TIS) for reporting serous fluid cytopathology. Our aims were to present the pooled... (Meta-Analysis)
Meta-Analysis
This is the first systematic review and meta-analysis of The International System (TIS) for reporting serous fluid cytopathology. Our aims were to present the pooled malignancy rate of each TIS reporting category and the diagnostic accuracy of cytology using this system. Database search using a predefined strategy was followed by study selection, data extraction, study quality assessment, and statistical analysis. Data derived from 16 eligible studies were pooled. The pooled rates of malignancy were as follows: 27% (95% CI; 16%-41%) for "nondiagnostic" (ND), 11% (95% CI; 7%-18%) for negative for malignancy" (NFM), 49% (95% CI; 37%-61%) for "atypia of undetermined significance" (AUS), 90% (95% CI; 81%-95%) for "suspicious for malignancy" (SFM), and 100% (95% CI; 98%-100%) for "positive for malignancy" (MAL). Studies performed exclusively in cancer hospitals showed higher pooled malignancy rates, compared with academic and community hospitals serving the general population, in the ND [40% (95% CI; 21%-62%) vs. 22% (95% CI; 11%-39%)], NFM [20% (95% CI; 13%-30%) vs. 9% (95% CI; 5%-17%)], and AUS categories [55% (95% CI; 47%-63%) vs. 46% (95% CI; 31%-62%)]. Notably, the difference was significant in the NFM category ( P =0.04). When both SFM and MAL cytology interpretations were considered as malignant outcomes, the pooled sensitivity and specificity were 68.74% (95% CI; 59.90%-76.39%) and 98.81% (95% CI; 98.18%-99.22%), respectively. In addition, the diagnostic odds ratio (DOR) was found to be 170.7 (95% CI; 96.2-303.3). Despite its strengths, our study also had some limitations. Therefore, future large-scale longitudinal studies could strengthen the findings of this review.
Topics: Humans; Cytodiagnosis; Neoplasms; Cytology
PubMed: 38695284
DOI: 10.1097/PAP.0000000000000454 -
Oral Diseases May 2024Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard,... (Review)
Review
Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.
PubMed: 38693620
DOI: 10.1111/odi.14962 -
The Journal of Clinical Endocrinology... Jun 2024Use of artificial intelligence (AI) to predict clinical outcomes in thyroid nodule diagnostics has grown exponentially over the past decade. The greatest challenge is in...
CONTEXT
Use of artificial intelligence (AI) to predict clinical outcomes in thyroid nodule diagnostics has grown exponentially over the past decade. The greatest challenge is in understanding the best model to apply to one's own patient population, and how to operationalize such a model in practice.
EVIDENCE ACQUISITION
A literature search of PubMed and IEEE Xplore was conducted for English-language publications between January 1, 2015 and January 1, 2023, studying diagnostic tests on suspected thyroid nodules that used AI. We excluded articles without prospective or external validation, nonprimary literature, duplicates, focused on nonnodular thyroid conditions, not using AI, and those incidentally using AI in support of an experimental diagnostic outside standard clinical practice. Quality was graded by Oxford level of evidence.
EVIDENCE SYNTHESIS
A total of 61 studies were identified; all performed external validation, 16 studies were prospective, and 33 compared a model to physician prediction of ground truth. Statistical validation was reported in 50 papers. A diagnostic pipeline was abstracted, yielding 5 high-level outcomes: (1) nodule localization, (2) ultrasound (US) risk score, (3) molecular status, (4) malignancy, and (5) long-term prognosis. Seven prospective studies validated a single commercial AI; strengths included automating nodule feature assessment from US and assisting the physician in predicting malignancy risk, while weaknesses included automated margin prediction and interobserver variability.
CONCLUSION
Models predominantly used US images to predict malignancy. Of 4 Food and Drug Administration-approved products, only S-Detect was extensively validated. Implementing an AI model locally requires data sanitization and revalidation to ensure appropriate clinical performance.
Topics: Thyroid Nodule; Humans; Artificial Intelligence; Thyroid Neoplasms
PubMed: 38679750
DOI: 10.1210/clinem/dgae277 -
Biomedicine & Pharmacotherapy =... Jun 2024Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2... (Review)
Review
Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2 diabetes mellitus, have been proven to reduce major adverse cardiovascular events, including cardiovascular death, in patients with heart failure irrespective of ejection fraction and independently of the hypoglycemic effect. Because of their favorable effects on the kidney and cardiovascular outcomes, their use has been expanded in all patients with any combination of diabetes mellitus type 2, chronic kidney disease and heart failure. Although mechanisms explaining the effects of these drugs on the cardiovascular system are not well understood, their effectiveness in all these conditions suggests that they act at the intersection of the metabolic, renal and cardiac axes, thus disrupting maladaptive vicious cycles while contrasting direct organ damage. In this systematic review we provide a state of the art of the randomized controlled trials investigating the effect of SGLT2i on cardiovascular outcomes in patients with chronic kidney disease and/or heart failure irrespective of ejection fraction and diabetes. We also discuss the molecular targets and signaling pathways potentially explaining the cardiac effects of these pharmacological agents, from a clinical and experimental perspective.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Animals; Heart Failure; Treatment Outcome; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic; Blood Glucose
PubMed: 38678962
DOI: 10.1016/j.biopha.2024.116650 -
The Journal of Hospital Infection Jun 2024Surgical site infections (SSIs) pose a frequent complication in cardiac surgery patients and lead to increased patient discomfort and extended hospitalization. This... (Meta-Analysis)
Meta-Analysis
Surgical site infections (SSIs) pose a frequent complication in cardiac surgery patients and lead to increased patient discomfort and extended hospitalization. This meta-analysis aimed to evaluate the protective role of single-use negative-pressure wound therapy (sNPWT) devices on closed surgical wounds after cardiac surgery, and explored their potential preventive application across all cardiac surgery patients. A comprehensive literature search was conducted on ScienceDirect, focusing on studies related to "negative pressure wound therapy" or "PICO negative pressure wound therapy" combined with "cardiac surgery" or "sternotomy," published between 2000 and 2022. Inclusion criteria encompassed case-control studies comparing sNPWT with traditional dressings on closed cardiac surgical incisions in adult patients undergoing median sternotomy without immediate postoperative infective complications, with available details on SSIs. A retrospective analysis of cases treated with sNPWT in our centre was also performed. The meta-analysis revealed a protective role of sNPWT, indicating a 44% risk reduction in overall SSIs (odds ratio 0.56) and a 40% risk reduction in deep wound infections (odds ratio 0.60). Superficial wound infections, however, showed non-significant protective effects. A single-centre study aligned with the meta-analysis findings, confirming the efficacy of sNPWT and was included in the meta-analysis. In conclusion, the meta-analysis and the single-centre study collectively support the protective role of negative pressure wound therapy against overall and deep SSIs, suggesting its potential prophylactic use on all cardiac surgery populations.
Topics: Humans; Cardiac Surgical Procedures; Negative-Pressure Wound Therapy; Retrospective Studies; Sternotomy; Surgical Wound Infection; Treatment Outcome; Adult
PubMed: 38677481
DOI: 10.1016/j.jhin.2024.04.003