-
The Lancet. Global Health Jun 2023Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests.
METHODS
In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337.
FINDINGS
We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies.
INTERPRETATION
AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples.
FUNDING
FIND, the Global Alliance for Diagnostics.
Topics: Humans; Male; Female; Sputum; Bayes Theorem; Cross-Sectional Studies; Tuberculosis; Lipopolysaccharides; HIV Infections; Sensitivity and Specificity; Mycobacterium tuberculosis
PubMed: 37202025
DOI: 10.1016/S2214-109X(23)00135-3 -
Stem Cells Translational Medicine Sep 2021Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this... (Meta-Analysis)
Meta-Analysis Review
Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this systematic review and meta-analysis summarized the effect of cell-based interventions in DKD animal models and treatment-related factors modifying outcomes. Electronic databases were searched for original investigations applying cell-based therapy in diabetic animals with kidney endpoints (January 1998-May 2019). Weighted or standardized mean differences were estimated for kidney outcomes and pooled using random-effects models. Subgroup analyses tested treatment-related factor effects for outcomes (creatinine, urea, urine protein, fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others (11%). Cell-based therapy significantly improved kidney function while reducing injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis, epithelial-mesenchymal-transition, oxidative stress). Preconditioning, xenotransplantation, and disease-source approaches were effective. MSC and UC/AF cells had greater effect on kidney function while cell products improved fibrosis. BM and UC/AF tissue sources more effectively improved kidney function and proteinuria vs adipose or other tissues. Cell dose, frequency, and administration route also imparted different benefits. In conclusion, cell-based interventions in diabetic animals improved kidney function and reduced injury with treatment-related factors modifying these effects. These findings may aid in development of optimal repair strategies through selective use of cells/products, tissue sources, and dose administrations to allow for successful adaptation of this novel therapeutic in human DKD.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Fibrosis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 34106528
DOI: 10.1002/sctm.19-0419 -
Medicina (Kaunas, Lithuania) Feb 2022Telomere length is an indicator of biological aging, and it shortens during cell division. A short telomere length is associated with various age-related diseases and... (Meta-Analysis)
Meta-Analysis Review
Telomere length is an indicator of biological aging, and it shortens during cell division. A short telomere length is associated with various age-related diseases and mortality. It is suggested that physical activity has a positive effect on the rate of telomere length shortening. Related studies, published in electronic databases, were searched with keywords, including exercise, telomere length, and randomized controlled trial. The data were weighted and pooled through a fixed-effect model. Of the total 49 studies searched, 7 studies with 939 participants were considered suitable, and were analyzed qualitatively and quantitatively. Exercise is beneficial to telomere length. Aerobic exercise was effective as the type of exercise (MD, -0.03; 95% CI, -0.04 to -0.01). In addition, exercise for more than 6 months, with a change in lifestyle, is beneficial for telomere length (MD, -0.02; 95% CI, -0.04 to -0.01). The type and duration of exercise for positive improvement in telomere length is aerobic exercise for more than 6 months.
Topics: Exercise; Humans; Life Style; Randomized Controlled Trials as Topic; Telomere
PubMed: 35208566
DOI: 10.3390/medicina58020242 -
Molecules (Basel, Switzerland) Apr 2023Magnolin is a naturally occurring, multi-bioactive lignan molecule with inherent anticancer effects. This study aims to summarize the botanical origins and anticancer... (Review)
Review
Magnolin is a naturally occurring, multi-bioactive lignan molecule with inherent anticancer effects. This study aims to summarize the botanical origins and anticancer properties of magnolin. For this, a recent (as of March 2023) literature review was conducted using various academic search engines, including PubMed, Springer Link, Wiley Online, Web of Science, Science Direct, and Google Scholar. All the currently available information about this phytochemical and its role in various cancer types has been gathered and investigated. Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways. In conclusion, magnolin showed robust anticancer activity against many cancer cell lines by altering several cancer signaling pathways in various non- and pre-clinical experimental models, making it a promising plant-derived chemotherapeutic option for further clinical research.
Topics: Humans; Lignans; Signal Transduction; Cell Cycle; Neoplasms; Phytochemicals
PubMed: 37175081
DOI: 10.3390/molecules28093671 -
Clinical and Translational Medicine Jan 2024The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes... (Review)
Review
BACKGROUND
The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes interact with immunocytes by secreting growth factors, cytokines, and chemokines, leading to wound healing, fibrosis, and escape of cancer immune surveillance. However, the specific mechanisms involved in the fibroblast-immunocyte interaction network have not yet been fully elucidated.
MAIN BODY AND CONCLUSION
Therefore, we systematically reviewed the molecular mechanisms of fibroblast-immunocyte interactions in fibrosis, from the history of cellular evolution and cell subtype divisions to the regulatory networks between fibroblasts and immunocytes. We also discuss how these communications function in different tissue and organ statuses, as well as potential therapies targeting the reciprocal fibroblast-immunocyte interplay in fibrosis. A comprehensive understanding of these functional cells under pathophysiological conditions and the mechanisms by which they communicate may lead to the development of effective and specific therapies targeting fibrosis.
Topics: Humans; Fibroblasts; Cross Reactions; Cell Division; Cytokines; Fibrosis
PubMed: 38264932
DOI: 10.1002/ctm2.1545 -
The Journal of Rheumatology Jul 2021To identify shared and distinct features of giant cell arteritis (GCA) and coronavirus disease 2019(COVID-19) to reduce diagnostic errors that could cause delays in...
OBJECTIVE
To identify shared and distinct features of giant cell arteritis (GCA) and coronavirus disease 2019(COVID-19) to reduce diagnostic errors that could cause delays in correct treatment.
METHODS
Two systematic literature reviews determined the frequency of clinical features of GCA and COVID-19 in published reports. Frequencies in each disease were summarized using medians and ranges.
RESULTS
Headache was common in GCA but was also observed in COVID-19 (GCA 66%, COVID-19 10%). Jaw claudication or visual loss (43% and 26% in GCA, respectively) generally were not reported in COVID-19. Both diseases featured fatigue (GCA 38%, COVID-19 43%) and elevated inflammatory markers (C-reactive protein [CRP] elevated in 100% of GCA, 66% of COVID-19), but platelet count was elevated in 47% of GCA but only 4% of COVID-19 cases. Cough and fever were commonly reported in COVID-19 and less frequently in GCA (cough, 63% for COVID-19 vs 12% for GCA; fever, 83% for COVID-19 vs 27% for GCA). Gastrointestinal upset was occasionally reported in COVID-19 (8%), rarely in GCA (4%). Lymphopenia was more common in COVID-19 than GCA (53% in COVID-19, 2% in GCA). Alteration of smell and taste have been described in GCA but their frequency is unclear.
CONCLUSION
Overlapping features of GCA and COVID-19 include headache, fever, elevated CRP and cough. Jaw claudication, visual loss, platelet count and lymphocyte count may be more discriminatory. Physicians should be aware of the possibility of diagnostic confusion. We have designed a simple checklist to aid evidence-based evaluation of patients with suspected GCA.
Topics: COVID-19; Diagnosis, Differential; Giant Cell Arteritis; Headache; Humans; Vision Disorders
PubMed: 33060304
DOI: 10.3899/jrheum.200766 -
Nutrients Mar 2022Telomere length (TL) is a robust marker of biological aging, and increased telomere attrition is noted in adults with obesity. The primary objective of this systematic... (Review)
Review
OBJECTIVE
Telomere length (TL) is a robust marker of biological aging, and increased telomere attrition is noted in adults with obesity. The primary objective of this systematic review was to summarize current knowledge on the effects of childhood obesity in TL. The secondary objective was to assess the effect of weight management interventions in TL.
METHODS
The following databases were searched: PubMed, Scopus, Web of Science and Heal-link.gr from inception to September 2021. The search was performed using the following combinations of terms: "telomer*" [All Fields] AND ("length" [All Fields] OR "lengths" [All Fields]) AND "obes*" [All Fields] AND ("child*" [All Fields] OR "adolescen*" [All Fields]).
RESULTS
A total of 16 original articles were included in this systematic review. Eleven of them were cross-sectional and five were lifestyle interventions.
CONCLUSIONS
There was a tendency towards a negative association between childhood obesity and TL. Life-style interventions in children have been associated with increased TL peripherally, indicating a possible association of the redistribution of younger cells in the periphery with the favorable effect of these interventions. Further prospective studies with larger sample sizes that employ other markers of cell aging would potentially elucidate this important mechanistic relation.
Topics: Adult; Aging; Child; Humans; Pediatric Obesity; Prospective Studies; Telomere; Telomere Homeostasis
PubMed: 35334902
DOI: 10.3390/nu14061244 -
Critical Reviews in Oncology/hematology Dec 2023The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised... (Meta-Analysis)
Meta-Analysis
Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials.
The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade > = 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Neoadjuvant Therapy; Platinum; Randomized Controlled Trials as Topic
PubMed: 37871779
DOI: 10.1016/j.critrevonc.2023.104190 -
Actas Urologicas Espanolas Nov 2022Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology. In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis.
MATERIALS AND METHODS
A systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS.
RESULTS
In total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively.
CONCLUSIONS
Our study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma.
Topics: Humans; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Transitional Cell; Hyaluronan Receptors; Keratin-20; Ki-67 Antigen; Tumor Suppressor Protein p53; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium
PubMed: 36216762
DOI: 10.1016/j.acuroe.2022.08.013 -
Current Oncology (Toronto, Ont.) Nov 2023Basal cell carcinoma (BCC) is the most common skin cancer, with a lifetime risk currently approaching up to 40% in Caucasians. Among these, some clinical and... (Review)
Review
Basal cell carcinoma (BCC) is the most common skin cancer, with a lifetime risk currently approaching up to 40% in Caucasians. Among these, some clinical and pathological BCC variants pose a higher risk due to their more aggressive biological behavior. Morpheaform BCC (morBCC), also known as sclerosing, fibrosing, or morpheic BCC, represents up to 5-10% of all BCC. Overall, morBCC carries a poorer prognosis due to late presentation, local tissue destruction, tumor recurrence, and higher frequency of metastasis. In this systematic review, we review the epidemiological, clinical, morphological, dermatoscopical, and molecular features of morBCC. After the title and abstract screening of 222 studies and the full-text review of 84 studies, a total of 54 studies met the inclusion criteria and were thus included in this review.
Topics: Humans; Neoplasm Recurrence, Local; Carcinoma, Basal Cell; Skin Neoplasms; Transcription Factors
PubMed: 37999140
DOI: 10.3390/curroncol30110720