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Medicina (Kaunas, Lithuania) Feb 2024IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage...
IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Glomerulonephritis, IGA; Angiotensin Receptor Antagonists; Nephrologists; Antihypertensive Agents; Kidney Failure, Chronic; Steroids; Immunosuppressive Agents
PubMed: 38399561
DOI: 10.3390/medicina60020274 -
Journal of Clinical Medicine Feb 2024Asthma and chronic obstructive pulmonary disease (COPD) are global health challenges leading to substantial morbidity and mortality. While existing guidelines emphasize... (Review)
Review
BACKGROUND
Asthma and chronic obstructive pulmonary disease (COPD) are global health challenges leading to substantial morbidity and mortality. While existing guidelines emphasize evidence-based treatments, the potential therapeutic role of thermal water (TW) inhalation remains under-investigated.
METHODS
This systematic review followed PRISMA-P guidelines and sought to evaluate the impact of TW in asthma and COPD. A thorough literature search, performed up to May 2023, encompassed in vitro, in vivo, randomized controlled trial (RCT), non-RCT, and observational studies.
RESULTS
The review included 12 studies reporting different findings. In vitro studies suggested TW could enhance antioxidant capacity and cell proliferation. In a murine model of non-atopic asthma, TW inhalation reduced airway hyperresponsiveness and inflammation. RCTs in COPD patients indicated mixed effects, including improved quality of life, reduced airway oxidant stress, and enhanced exercise tolerance. Asthma patients exposed to water aerosols exhibited improved lung function and reduced airway inflammation. Non-RCTs showed improved lung function and antioxidant activity after TW therapy. Additionally, observational studies reported enhanced lung function and reduced airway inflammation.
CONCLUSION
The current evidence suggests potential benefits of TW therapy in asthma and COPD. However, limited high-quality RCTs and concerns regarding occupational TW exposure necessitate further investigation. While TW therapy offers a non-invasive treatment, its therapeutic potential still needs definitive demonstration. Future research should therefore prioritize well-designed RCTs to thoroughly establish the efficacy and safety of TW as a potential therapeutic intervention for asthma and COPD.
PubMed: 38398384
DOI: 10.3390/jcm13041071 -
Journal of Clinical Medicine Feb 2024Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result...
Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli-Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review.
Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the gene (c.77delT) and a likely pathogenic missense variant in the gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads ( = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases ( = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.
PubMed: 38398243
DOI: 10.3390/jcm13040929 -
Frontiers in Oncology 2024Radiomics, an emerging field, presents a promising avenue for the accurate prediction of biomarkers in different solid cancers. Lung cancer remains a significant global...
BACKGROUND
Radiomics, an emerging field, presents a promising avenue for the accurate prediction of biomarkers in different solid cancers. Lung cancer remains a significant global health challenge, contributing substantially to cancer-related mortality. Accurate assessment of Ki-67, a marker reflecting cellular proliferation, is crucial for evaluating tumor aggressiveness and treatment responsiveness, particularly in non-small cell lung cancer (NSCLC).
METHODS
A systematic review and meta-analysis conducted following the preferred reporting items for systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guidelines. Two authors independently conducted a literature search until September 23, 2023, in PubMed, Embase, and Web of Science. The focus was on identifying radiomics studies that predict Ki-67 expression in lung cancer. We evaluated quality using both Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Radiomics Quality Score (RQS) tools. For statistical analysis in the meta-analysis, we used STATA 14.2 to assess sensitivity, specificity, heterogeneity, and diagnostic values.
RESULTS
Ten retrospective studies were pooled in the meta-analysis. The findings demonstrated that the use of computed tomography (CT) scan-based radiomics for predicting Ki-67 expression in lung cancer exhibited encouraging diagnostic performance. Pooled sensitivity, specificity, and area under the curve (AUC) in training cohorts were 0.78, 0.81, and 0.85, respectively. In validation cohorts, these values were 0.78, 0.70, and 0.81. Quality assessment using QUADAS-2 and RQS indicated generally acceptable study quality. Heterogeneity in training cohorts, attributed to factors like contrast-enhanced CT scans and specific Ki-67 thresholds, was observed. Notably, publication bias was detected in the training cohort, indicating that positive results are more likely to be published than non-significant or negative results. Thus, journals are encouraged to publish negative results as well.
CONCLUSION
In summary, CT-based radiomics exhibit promise in predicting Ki-67 expression in lung cancer. While the results suggest potential clinical utility, additional research efforts should concentrate on enhancing diagnostic accuracy. This could pave the way for the integration of radiomics methods as a less invasive alternative to current procedures like biopsy and surgery in the assessment of Ki-67 expression.
PubMed: 38384802
DOI: 10.3389/fonc.2024.1329801 -
Dermatology Practical & Conceptual Jan 2024Diffuse Melanosis Cutis (DMC) is a rare and late complication of metastatic malignant melanoma (MM) characterized by progressive pigmentation of skin and sometimes... (Review)
Review
INTRODUCTION
Diffuse Melanosis Cutis (DMC) is a rare and late complication of metastatic malignant melanoma (MM) characterized by progressive pigmentation of skin and sometimes mucous membranes. The distinctive feature is the widespread and progressive deposition of melanin precursors in the dermis.
OBJECTIVES
The purpose of this review is to define the clinical and demographic features of DMC and to promote a deeper insight into the clinical manifestation, histological findings, and pathophysiology behind DMC.
METHODS
We have conducted a systematic review of the literature on published DMC in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We also reported a case of DMC secondary to low-risk melanoma.
RESULTS
Overall, including our case report, we reported 53 articles described 62 DMC patients. Breslow level of primary melanoma was reported having a mean value of 3.3 mm. The mean survival rate from onset of DMC resulted being 4.36 months.
CONCLUSIONS
Among the most widely accepted etiopathogenetic hypotheses are deposition of melanic precursors in the dermis following tumor lysis, melanocyte proliferation induced by neoplastic growth factors, and the presence of diffuse dermal micro-metastases of MM. However, unanimous consensus on the proposed etiopathogenetic models of DMC is still lacking.
PubMed: 38364426
DOI: 10.5826/dpc.1401a8 -
Kidney International Reports Feb 2024IgA nephropathy's (IgAN's) MEST-C classification relationship with complement activation is still not fully understood because of limited and conflicting evidence. Our...
INTRODUCTION
IgA nephropathy's (IgAN's) MEST-C classification relationship with complement activation is still not fully understood because of limited and conflicting evidence. Our study aimed to delineate this relationship through a systematic review.
METHODS
We adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines and conducted a systematic review, utilizing databases like MEDLINE (PubMed), Embase, Scopus, and Cochrane from January 2016 (year of updated MEST-C classification) to January 2023. We specifically selected studies that employed established methods to evaluate complement activation and the MEST-C classification.
RESULTS
A total of 34 studies with 10,082 patients were included. Among these, 7 studies focused on the pediatric population (500 patients), and 22 studies involved 8128 patients from Asian populations. C4d, C3, C5b9, MBL, C4, and factor H-related protein 5 (FHR5) were the most frequently studied complement proteins in relation to the MEST-C classification. Complement activation assessment was primarily conducted using immunofluorescence and immunohistochemistry on kidney biopsy specimens. All complement proteins investigated showed associations with the C1-2 class. Notably, FB, FH, MASP1/3, MASP2, C5a, and C5b9 from the alternative, lectin, and terminal pathways were uniquely present in the C1-2 class. Whereas C3, FHR5, C4, and C4d were associated with all the MEST-C classes.
CONCLUSION
We found evidence supporting the involvement of alternative and lectin complement pathways across all MEST-C classes. All examined complement factors were associated with the C1-2 class, emphasizing the critical role of complement activation, possibly at the endothelial surface. These findings may guide the development of personalized treatment strategies targeting complement pathways in relation to the MEST-C lesions.
PubMed: 38344730
DOI: 10.1016/j.ekir.2023.11.005 -
Medical Image Analysis Apr 2024With the massive proliferation of data-driven algorithms, such as deep learning-based approaches, the availability of high-quality data is of great interest. Volumetric...
With the massive proliferation of data-driven algorithms, such as deep learning-based approaches, the availability of high-quality data is of great interest. Volumetric data is very important in medicine, as it ranges from disease diagnoses to therapy monitoring. When the dataset is sufficient, models can be trained to help doctors with these tasks. Unfortunately, there are scenarios where large amounts of data is unavailable. For example, rare diseases and privacy issues can lead to restricted data availability. In non-medical fields, the high cost of obtaining enough high-quality data can also be a concern. A solution to these problems can be the generation of realistic synthetic data using Generative Adversarial Networks (GANs). The existence of these mechanisms is a good asset, especially in healthcare, as the data must be of good quality, realistic, and without privacy issues. Therefore, most of the publications on volumetric GANs are within the medical domain. In this review, we provide a summary of works that generate realistic volumetric synthetic data using GANs. We therefore outline GAN-based methods in these areas with common architectures, loss functions and evaluation metrics, including their advantages and disadvantages. We present a novel taxonomy, evaluations, challenges, and research opportunities to provide a holistic overview of the current state of volumetric GANs.
Topics: Humans; Algorithms; Rare Diseases; Data Analysis
PubMed: 38340545
DOI: 10.1016/j.media.2024.103100 -
Cancers Jan 2024Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be... (Review)
Review
Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be effective in cancer prevention and treatment. Among bioactive flavonoids found in fruits and vegetables, kaempferol (KMP) is known for its anti-inflammatory, antioxidant, and anticancer properties. This systematic review aims to highlight the potential therapeutic effects of KMP on different types of solid malignant tumors. This review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Science Direct, Scopus, and Google Scholar. After the application of study criteria, 64 studies were included. In vitro experiments demonstrated that KMP exerts antitumor effects by controlling tumor cell cycle progression, proliferation, apoptosis, migration, and invasion, as well as by inhibiting angiogenesis. KMP was also able to inhibit important markers that regulate epithelial-mesenchymal transition and enhanced the sensitivity of cancer cells to traditional drugs used in chemotherapy, including cisplatin and 5-fluorouracil. This flavonoid is a promising therapeutic compound and its combination with current anticancer agents, including targeted drugs, may potentially produce more effective and predictable results.
PubMed: 38339336
DOI: 10.3390/cancers16030585 -
Cureus Jan 2024Sulindac sulfone, an active metabolite of sulindac, a non-steroidal anti-inflammatory drug, has good anti-inflammatory potential. The antineoplastic effect of sulindac... (Review)
Review
Sulindac sulfone, an active metabolite of sulindac, a non-steroidal anti-inflammatory drug, has good anti-inflammatory potential. The antineoplastic effect of sulindac sulfone is mediated through a cyclooxygenase inhibitory mechanism, followed by apoptosis and inhibition of cell proliferation. Mounting studies have explored the anti-neoplastic effect of sulindac sulfone in various types of cancers in a dose-dependent manner. In this backdrop, we have conducted a systematic review to evaluate the efficacy and dose of sulindac sulfone as an anti-neoplastic agent in human head and neck squamous cell carcinoma cell lines (HNSCCs). In this study, we used a systematic literature review approach, and articles were searched in PubMed, and Medline with the keywords "sulindac sulfone," "anti-neoplastic activity," "chemopreventive," and "head and neck squamous cell carcinoma". A hand-search of journals was also performed. Articles were reviewed and analyzed. The analysis reveals that, based on the in vitro studies on various tumor models, the optimum concentration of sulindac sulfone which elicits anti-neoplastic effects is 200-800 µM. The anti-neoplastic effect is mediated through inhibition of cell proliferation and apoptosis. The results of our systematic review show that the anti-neoplastic activity of pharmacologic Sulindac sulfone is part of its dose-dependent activity, which can be safely employed in the therapy for human HNSCCs and would be responsible for a beneficial outcome of the treatment.
PubMed: 38313951
DOI: 10.7759/cureus.51692 -
Journal of Oral and Maxillofacial... 2023The primary goal of this systematic analysis is to determine the predictive significance of proliferative markers in surgical margins of patients with oral squamous cell... (Review)
Review
The primary goal of this systematic analysis is to determine the predictive significance of proliferative markers in surgical margins of patients with oral squamous cell carcinoma (OSCC). A thorough literature search was done on databases like MEDLINE/Pub-Med, Cochrane and Scopus libraries for similar studies until December 2022. All the relevant original research studies (retrospective and prospective) published in the literature assessing the predictive value of proliferative markers in surgical margins in OSCC were included. Seventeen studies with 1159 patients were included. The research included here used p53, p44/p42, proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), Ki-67, Bcl2, Nibrin, AgNORs, Cyclin B1, Cornulin, ISG 15antibodies, MCM3 in OSCC. Four studies were done on oral premalignant lesions and OSCC. Among these studies, Ki-67 was the most accurate, followed by p53 (75%) and AgNORs, while PCNA had the least accuracy. To minimize the risk of bias panel of antibodies was suggested in most studies. For interobserver variability, analysis of variance and Chi-square test were used in most studies. The chance of recurrence rate was calculated using a log-rank test and a Kaplan-Meier curve. The significance of proliferative markers in surgical margins of OSCC has been emphasized in the present review. Future research should focus on selecting antibodies, preferably a panel, with a large sample size and extended follow-up.
PubMed: 38304496
DOI: 10.4103/jomfp.jomfp_390_23