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Clinical Genitourinary Cancer May 2024The number of cancer patients undergoing chronic treatment with target therapy is increasing. Although much is known about the toxicity of conventional anticancer... (Review)
Review
The number of cancer patients undergoing chronic treatment with target therapy is increasing. Although much is known about the toxicity of conventional anticancer therapies, evidence on the effects of tyrosine kinase inhibitors (TKIs) on fertility is still lacking. Therefore, this review was undertaken to evaluate the effects of TKIs on male gonadal function. A comprehensive search of PubMed and Scopus databases was conducted, focusing on the effects of TKIs on spermatogenesis and testicular endocrine function. We included animal studies, observational studies, and case reports published up to December 31, 2023. Identified articles were reviewed and analyzed to evaluate the impact of TKIs on the male gonad. Their long-term effects, the reversibility of the observed changes, and the underlying molecular mechanisms involved were recorded. The findings emerging on the effects of TKIs on male gonadal function are conflicting. Although specific TKIs (imatinib, gefitinib, sorafenib, sunitinib, quizartinib, dasatinib, and nilotinib) have been identified as potentially as potential interfering with spermatogenesis and hormone production, the extent and severity of these effects may vary from patient to patient and between different drugs within this drug class. Experimental studies on mouse models have suggested a potential interference with spermatogenesis. Evidence also suggests that TKIs affects the hypothalamic-pituitary-testicular axis, decreasing serum testosterone and gonadotropin levels. The effects of TKIs on male gonadal function highlight the need for personalized treatment choices. Potential fertility concerns can help minimize adverse effects and improve patient outcomes. Addressing the potential impact of TKIs on male fertility helps optimize cancer treatment and survival outcomes.
PubMed: 38901138
DOI: 10.1016/j.clgc.2024.102131 -
Scientific Reports Jun 2024The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight... (Meta-Analysis)
Meta-Analysis
The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).
Topics: Humans; Abortion, Habitual; Heparin, Low-Molecular-Weight; Female; Pregnancy; Aspirin; Anticoagulants; Randomized Controlled Trials as Topic; Live Birth
PubMed: 38898143
DOI: 10.1038/s41598-024-62949-5 -
European Urology Focus Jun 2024Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited... (Review)
Review
BACKGROUND AND OBJECTIVE
Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited sensitivity, resulting in a substantial burden. Thus, noninvasive biomarkers have been investigated, among which DNA methylation has shown promise. This systematic review and meta-analysis sought to assess the diagnostic accuracy of DNA methylation biomarkers reported in the literature for bladder cancer detection, pinpointing the most informative one.
METHODS
The search for this systematic review and meta-analysis was conducted on PubMed, Scopus, and Cochrane Library for relevant studies published until December 31, 2022. A meta-analysis was performed using a random-effect model, to compute the pooled sensitivity and specificity of the markers. PROSPERO's registration ID for the study is CRD42023397703.
KEY FINDINGS AND LIMITATIONS
Out of the 2297 studies retrieved, 68 were included in the final analysis, despite considerable heterogeneity. These involved 12 696 participants, of whom 5557 were diagnosed with bladder cancer. Using diagnostic odds ratio (DOR) as a comparative measure, the five most promising markers (pooled sensitivity, specificity, and DOR) were SALL3 (61%, 97%, and 55.67, respectively), PENK (77%, 93%, and 47.90, respectively), ZNF154 (87%, 90%, and 45.07, respectively), VIM (82%, 90%, and 44.81, respectively), and POU4F2 (81%, 89%, and 34.89, respectively). Urinary cytology identified bladder cancer with 55% sensitivity, 92% specificity, and 14.37 DOR.
CONCLUSIONS AND CLINICAL IMPLICATIONS
DNA methylation biomarkers disclose high accuracy for bladder cancer detection in urine. Nonetheless, validation studies in different clinical settings are scarce, hampering clinical use. The identified biomarkers should be prioritized in future validation studies.
PATIENT SUMMARY
In this meta-analysis, we include previously published studies that used urine samples of bladder cancer patients' from all around the globe. We were able to compare the diagnostic accuracy of noninvasive markers across different populations. We were able to conclude on the most promising DNA methylation markers to detect bladder cancer using urine.
PubMed: 38897871
DOI: 10.1016/j.euf.2024.05.024 -
Seizure Jun 2024To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs).
OBJECTIVE
To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs).
METHODS
This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed.
RESULTS
The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old.
CONCLUSION
Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group.
PubMed: 38897163
DOI: 10.1016/j.seizure.2024.06.013 -
Frontiers in Oncology 2024Breast cancer is a significant public health issue, exhibiting the most pronounced occurrence and fatality rates among malignant neoplasms globally. Targeted therapy is...
BACKGROUND
Breast cancer is a significant public health issue, exhibiting the most pronounced occurrence and fatality rates among malignant neoplasms globally. Targeted therapy is a medical intervention that focuses on specific molecular markers. This study aims to investigate and evaluate the current research trends and directions in the field of targeted therapy for breast cancer using bibliometric analysis.
METHOD
The Web of Science database was utilized to retrieve relevant articles published between 2003 and 2022. The VOSviewer software and Bibliometrix package in the R language were employed to conduct co-occurrence and clustering analyses of authors, countries, institutions, journals, references, and the CiteSpace tool was utilized for keyword burst detection.
RESULTS
A total of 2,258 articles were included and the annual number of publications increased rapidly. The most prolific country on this topic was the USA (n=898, 39.77%) and the University of Texas MD Anderson Cancer Center published most papers (n=93). Dennis J. Slamon and Gabriel N. Hortobagyi stood out in the field, with Dennis J. Slamon leading in terms of co-citations(n=653) and Gabriel N. Hortobagyi topping the list in terms of published articles(n=18). The most productive journal was Breast Cancer Research and Treatment and the most cited journal was Journal of Clinical Oncology. The clustering of keywords indicated that the primary focus of researches in the past two decades was on the development and clinical evaluation of tumor-targeted drugs associated with the epidermal growth factor receptor (EGFR) family signaling pathway, and explored mechanisms related to biological behavior of breast cancer. Keywords co-occurrence and burst analysis identified current research hotspots and potential research trends.
CONCLUSION
This study employed bibliometric analysis to examine research on targeted therapy for breast cancer over a span of 20 years, and identified development trends of research and elucidated potential research trajectories in the domain of this topic. This study helps in the identification of prospective collaborators and partner institutions for researchers.
PubMed: 38894873
DOI: 10.3389/fonc.2024.1366900 -
Diagnostics (Basel, Switzerland) May 2024Neck infections are often prone to being underestimated and can manifest insidiously. The spread of infection can lead to translocation into thoracic areas, causing... (Review)
Review
Neck infections are often prone to being underestimated and can manifest insidiously. The spread of infection can lead to translocation into thoracic areas, causing descending necrotizing mediastinitis (DNM). However, the application of the post-mortem approach in such cases is not well-described in the literature. A literature review was carried out according to the PRISMA methods. Nine papers were included in the final review, revealing different levels of involvement of neck layers that can be linked to different causes. Expertise with respect to the anatomy of the fasciae and spaces of the neck enables an understanding of the pathogenesis of DNM. However, a clear autoptic description was not provided in any of the articles. Therefore, we also employed a practical post-mortem approach to cases of death due to DNM. It is fundamental for pathologists to identify the exact head and neck structures involved. Providing dissectors with support from an otolaryngologist could be useful. This paper could help address such difficult cases.
PubMed: 38893677
DOI: 10.3390/diagnostics14111150 -
Diagnostics (Basel, Switzerland) May 2024Sudden unexpected deaths often remain unresolved despite forensic examination, posing challenges for pathologists. Molecular autopsy, through genetic testing, can reveal... (Review)
Review
Sudden unexpected deaths often remain unresolved despite forensic examination, posing challenges for pathologists. Molecular autopsy, through genetic testing, can reveal hidden causes undetectable by standard methods. This review assesses the role of molecular autopsy in clarifying SUD cases, examining its methodology, utility, and effectiveness in autopsy practice. This systematic review followed PRISMA guidelines and was registered with PROSPERO (registration number: CRD42024499832). Searches on PubMed, Scopus, and Web of Science identified English studies (2018-2023) on molecular autopsy in sudden death cases. Data from selected studies were recorded and filtered based on inclusion/exclusion criteria. Descriptive statistics analyzed the study scope, tissue usage, publication countries, and journals. A total of 1759 publications from the past 5 years were found, with 30 duplicates excluded. After detailed consideration, 1645 publications were also excluded, leaving 84 full-text articles for selection. Out of these, 37 full-text articles were chosen for analysis. Different study types were analyzed. Mutations were identified in 17 studies, totaling 47 mutations. Molecular investigations are essential when standard exams fall short in determining sudden death causes. Expertise in molecular biology is crucial due to diverse genetic conditions. Discrepancies in post-mortem protocols affect the validity of results, making standardization necessary. Multidisciplinary approaches and the analysis of different tissue types are vital.
PubMed: 38893676
DOI: 10.3390/diagnostics14111151 -
Journal of Clinical Medicine Jun 2024Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an emerging technique for delivering chemotherapy directly to the peritoneum via a pressurized aerosol. Its... (Review)
Review
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an emerging technique for delivering chemotherapy directly to the peritoneum via a pressurized aerosol. Its growing attention stems from its effectiveness in treating peritoneal carcinomatosis (PC) originating from various primary tumors, with gastric cancer (GC) being among the most prevalent. This study aimed to systematically investigate PIPAC's therapeutic role in gastric cancer peritoneal metastasis (GCPM). The systematic review and meta-analysis followed the PRISMA 2020 guidelines, searching Pubmed, Web of Science, and SCOPUS databases. The meta-analysis of relative risks and mean differences compared patients undergoing one or two PIPAC sessions with those completing three or more, assessing various outcomes. Eighteen studies underwent qualitative analysis, and four underwent quantitative analysis. Patients with three or more PIPAC procedures had shorter hospital stays (MD = -1.2; 95%CI (-1.9; -0.5); < 0.001), higher rates of histopathological response (RR = 1.77, 95%CI 1.08; 2.90; = 0.023), and significantly improved overall survival (MD = 6.0; 95%CI 4.2; 7.8; < 0.001). Other outcomes showed no significant differences. PIPAC demonstrated efficacy in carefully selected patients, enhancing histopathologic response rates and overall survival without prolonging hospital stays. This study underscores the necessity for randomized controlled trials and precise selection criteria to refine PIPAC's implementation in clinical practice.
PubMed: 38893031
DOI: 10.3390/jcm13113320 -
Journal of Clinical Medicine Jun 2024: The Carlevale lens (FIL SSF, Soleko IOL Division, Italy) is a new lens for suture-less scleral fixation. This paper aimed to systematically review articles on this... (Review)
Review
: The Carlevale lens (FIL SSF, Soleko IOL Division, Italy) is a new lens for suture-less scleral fixation. This paper aimed to systematically review articles on this lens, the surgical techniques used for its implantation, complications and outcomes. : This systematic review was performed following the PRISMA guidelines. The search string used was "Carlevale" AND "scleral fixation" from inception until March 2024. For completeness, either case-control studies, case reports or case series written in English were included. The authors used the Newcastle-Ottawa scale for the case-control studies and the JBI Critical Appraisal Checklist for case reports and case series. : Twenty-nine articles were included. Scleral fixation with Carlevale lens can be performed by creating scleral flaps or, alternatively, by using scleral pockets. The two sclerotomies must be diametrically opposed, and are preferably created by 25-gauge trocars. A pars plana vitrectomy should be performed every time, and the design of the lens should be suitable for self-anchoring to the sclera; the most accredited strategy to achieve this is to avoid scleral sutures. There were only a few intraoperative and postoperative complications reported; vitreous hemorrhages were the most frequent intraoperative events, while the most relevant postoperative complications were vitreous hemorrhages, cystoid macular oedema and transient variations in the intraocular pressure. Excellent results have been obtained in terms of BCVA, IOL centration and stability, mean intraocular pressure, postoperative spherical equivalent, separation between anterior and posterior chamber and the distance of the IOL from anterior chamber structures. : The foldable hydrophilic design of the Carlevale lens has shown good effectiveness, IOL stability and few intra and post-operative complications.
PubMed: 38892997
DOI: 10.3390/jcm13113287 -
Journal of Clinical Medicine May 2024: There are limited data on the risks and benefits of using Andexanet alfa (AA) compared with four-factor prothrombin complex concentrate (4F-PCC) for the reversal of... (Review)
Review
Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies.
: There are limited data on the risks and benefits of using Andexanet alfa (AA) compared with four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitor-associated intracranial hemorrhage (ICH). Our aim was to describe a compilation of the information available in the literature to date. : PubMed, Embase, Web of Science (Clarivate Analytics) and the Cochrane Central Register of Controlled Trials were searched until December 2023. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review included studies that were retrospective in design and evaluated both drugs to control bleeding and complications (death and thromboembolic events). Two researchers re-examined the studies for relevance, extracted the data and assessed the risk of bias. No meta-analyses were performed for the results. : In this limited patient sample, we found no differences between published articles in terms of neuroimaging stability or thrombotic events. However, some studies show significant differences in mortality, suggesting that one of the AAs may be superior to 4F-PCC. : Our qualitative analysis shows that AA has a better efficacy profile compared with 4F-PCC. However, further studies monitoring these patients and a multicenter collaborative network dedicated to this topic are needed.
PubMed: 38892788
DOI: 10.3390/jcm13113077