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International Journal of Molecular... May 2024Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell)... (Meta-Analysis)
Meta-Analysis Review
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Topics: Multiple Myeloma; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Treatment Outcome; Quality of Life; Neoplasm Recurrence, Local; Cytokine Release Syndrome
PubMed: 38732213
DOI: 10.3390/ijms25094996 -
Journal of Thrombosis and Thrombolysis May 2024COVID-19 has been associated with alterations in coagulation. Recent reports have shown that protein C and S activities are altered in COVID-19. This may affect the... (Review)
Review
COVID-19 has been associated with alterations in coagulation. Recent reports have shown that protein C and S activities are altered in COVID-19. This may affect the complications and outcome of the disease. However, their exact role in COVID-19 remains uncertain. The aim of the current study was therefore to analyze all papers in the literature on protein C and S activities in COVID-19. We searched three medical electronic databases. Of the 2442 papers, 28 studies were selected for the present meta-analysis. For the meta-analysis, means ± standard deviations with 95% confidence intervals (CI) for protein C and S activities were extracted. Pooled p values were calculated using STATA software. Protein C and S activities were significantly lower in COVID-19 patients than in healthy controls (pooled p values: 0.04 and 0.02, respectively). Similarly, protein C activities were considerably lower in nonsurviving patients (pooled p value = 0.00). There was no association between proteins C or S and thrombosis risk or ICU admission in COVID-19 patients (p value > 0.05). COVID-19 patients may exhibit lower activities of the C and S proteins, which might affect disease outcome; however, additional attention should be given when considering therapeutic strategies for these patients.
PubMed: 38722521
DOI: 10.1007/s11239-024-02971-6 -
Viral Immunology May 2024In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated... (Meta-Analysis)
Meta-Analysis
In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated orthopoxvirus vaccine that has been authorized by the U.S. Food and Drug Administration as the vaccine of choice for the prevention of mpox. In this study, we conducted a meta-analysis of all currently published literature on the efficacy and safety of the MVA-BN vaccine in the real world, showing that the MVA-BN vaccine is effective and safe, with efficacy of up to 75% with a single dose and up to 80% with a two-dose vaccine. Meanwhile, we found that subcutaneous injection has lower local and systemic adverse events than intradermal injection, regardless of single- or two-dose vaccination, and subcutaneous injection is better tolerated in children, the elderly, or people with underlying medical conditions. These results have important reference value for clinical practice.
Topics: Humans; Vaccine Efficacy; Vaccines, Attenuated; Poxviridae Infections; Vaccinia virus; Vaccination; Injections, Subcutaneous; Injections, Intradermal; Viral Vaccines; Orthopoxvirus; Child
PubMed: 38717823
DOI: 10.1089/vim.2023.0147 -
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 -
European Journal of Surgical Oncology :... Jul 2024Inflammatory myofibroblastic tumor (IMT) is a soft tissue neoplasm which can be locally invasive, recur, or in rare cases metastasize. Often originating from the abdomen... (Review)
Review
Inflammatory myofibroblastic tumor (IMT) is a soft tissue neoplasm which can be locally invasive, recur, or in rare cases metastasize. Often originating from the abdomen or thorax, IMT most commonly affects children and young adults. Due to its rarity comprehensive reports detailing clinical management and outcome(s) are sparse and often based on limited index case numbers. This study systematically analyzes outcome metrics of pediatric IMT and identifies risk factors for mortality. Medline/Embase databases were searched in accordance with PRISMA guidelines. Final analysis included 57 studies with 673 IMT patients (355 males, 53 %). Individual patient data was available for 405 cases with a median follow-up period of 36 months. Tumor sites included abdomen/pelvis (n = 233, 58 %), thorax (n = 125, 31 %), head/neck (n = 34, 8 %), and extremities (n = 13, 3 %). Surgical tumor resection was the mainstay of treatment, while only 20 patients (5 %) were treated non-operatively. Recurrence(s) were reported in 80 patients (20 %) with 34 (12 %) requiring reoperation. Positive tumor margins were a significant risk factor for tumor recurrence (p < 0.0001). Chemo/radiotherapy was reported in 98 patients (25 %). Most patients (94 %) survived; 81 % (n = 237) with no evidence of recurrent disease, 14 % (n = 41) were alive with disease, and 25 (6 %) died of disease. Positive margins at primary operation, and metastatic disease were associated with mortality (p < 0.0001 for both). IMT is a rare tumor with favorable outcome for the majority of patients. Whilst most patients will present with benign tumors, complete surgical resection (R0) is crucial, as positive surgical margins are a significant risk factor for tumor recurrence and mortality.
Topics: Humans; Child; Neoplasm Recurrence, Local; Margins of Excision; Granuloma, Plasma Cell; Risk Factors; Abdominal Neoplasms; Head and Neck Neoplasms; Thoracic Neoplasms; Soft Tissue Neoplasms; Reoperation; Neoplasms, Muscle Tissue
PubMed: 38713995
DOI: 10.1016/j.ejso.2024.108388 -
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