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Frontiers in Pharmacology 2024Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer...
Efficacy and safety of PARP inhibitors combined with antiangiogenic agents in the maintenance treatment of ovarian cancer: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.
Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer (OC). However, there is currently a lack of evidence-based study to directly compare the effects of combination therapy with these two drugs. Therefore, this study aimed to compare the efficacy and safety of combination therapy with PARP inhibitors and antiangiogenic agents in women with OC using a meta-analysis. An exhaustive search of literature was undertaken using multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library to identify pertinent randomized controlled trials (RCTs) published up until 17 December 2023. The data on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled. We computed the pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for PFS and OS, along with the relative risks (RRs) and 95% CIs for AEs. Trial sequential analysis, heterogeneity test, sensitivity analysis, and publication bias assessment were performed. Stata 12.0 and Software R 4.3.1 were utilized for all analyses. This meta-analysis included 7 RCTs with a total of 3,388 participants. The overall analysis revealed that combination therapy of PARP inhibitors and antiangiogenic agents significantly improved PFS (HR = 0.615, 95% CI = 0.517-0.731; 95% PI = 0.379-0.999), but also increased the risk of AEs, including urinary tract infection (RR = 1.500, 95% CI = 1.114-2.021; 95% PI = 0.218-10.346), fatigue (RR = 1.264, 95% CI = 1.141-1.400; 95% PI = 1.012-1.552), headache (RR = 1.868, 95% CI = 1.036-3.369; 95% PI = 0.154-22.642), anorexia (RR = 1.718, 95% CI = 1.320-2.235; 95% PI = 0.050-65.480), and hypertension (RR = 5.009, 95% CI = 1.103-22.744; 95% PI = 0.016-1580.021) compared with PARP inhibitor or antiangiogenic agent monotherapy. Our study has not yet confirmed the benefit of combination therapy on OS in OC patients (HR = 0.885, 95% CI = 0.737-1.063). Additionally, subgroup analyses further showed that combination therapy resulted in an increased risk of AEs, encompassing thrombocytopenia, vomiting, abdominal pain, proteinuria, fatigue, headache, anorexia, and hypertension (all < 0.05). Our study demonstrated the PFS benefit of combination therapy with PARP inhibitors and antiangiogenic agents in patients with OC. The OS result need to be updated after the original trial data is mature. Clinicians should be vigilant of AEs when administering the combination therapy in clinical practice. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023494482.
PubMed: 38584601
DOI: 10.3389/fphar.2024.1372077 -
Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487 -
BMC Urology Mar 2024The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy.
METHODS
Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework.
RESULTS
Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05).
CONCLUSIONS
Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy.
TRIAL REGISTRATION
The PROSPERO registration number is CRD42022361883.
Topics: Humans; Leflunomide; Glomerulonephritis, IGA; Immunosuppressive Agents; Adrenal Cortex Hormones; Glomerular Filtration Rate
PubMed: 38468247
DOI: 10.1186/s12894-024-01438-3 -
The Lancet. Microbe Apr 2024Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infections, respectively. We aimed to collate all available evidence on the accuracy of other proposed diagnostic techniques.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane Library, and LILACS for studies published from database inception to Dec 31, 2022, investigating the sensitivity and specificity of diagnostic tests for S haematobium and S mansoni infections against Kato-Katz thick smears or urine microscopy (reference tests) involving adults (aged ≥18 years), school-aged children (aged 7 to 18 years), or preschool-aged children (aged 1 month to 7 years). We extracted raw data on true positives, true negatives, false positives, and false negatives for the diagnostic tests and data on the number of participants, study authors, publication year, journal, study design, participants' age and sex, prevalence of Schistosoma infection, and treatment status. To account for imperfect reference tests, we used a hierarchical Bayesian latent class meta-analysis to model test accuracy.
FINDINGS
Overall, we included 121 studies, assessing 28 different diagnostic techniques. Most studies (103 [85%] of 121) were done in Africa, 14 (12%) in South America, one (1%) in Asia, and one (1%) in an unknown country. Compared with the reference test, Kato-Katz thick smears, circulating cathodic antigen urine cassette assay version 1 (CCA1, 36 test comparisons) had excellent sensitivity (95% [95% credible interval 88-99]) and reasonable specificity (74% [63-83]) for S mansoni. ELISA-based tests had a performance comparable to circulating cathodic antigen, but there were few available test comparisons. For S haematobium, proteinuria (42 test comparisons, sensitivity 73% [62-82]; specificity 94% [89-98]) and haematuria (75 test comparisons, sensitivity 85% [80-90]; specificity 96% [92-99]) reagent strips showed high specificity, with haematuria reagent strips having better sensitivity. Despite limited data, nucleic acid amplification tests (NAATs; eg, PCR or loop-mediated isothermal amplification [LAMP]) showed promising results with sensitivity estimates above 90%. We found an unclear risk of bias of about 70% in the use of the reference or index tests and of 50% in patient selection. All analyses showed substantial heterogeneity (I>80%).
INTERPRETATION
Although NAATs and immunological diagnostics show promise, the limited information available precludes drawing definitive conclusions. Additional research on diagnostic accuracy and cost-effectiveness is needed before the replacement of conventional tests can be considered.
FUNDING
WHO and Luxembourg Institute of Health.
Topics: Child; Child, Preschool; Adult; Animals; Humans; Adolescent; Schistosoma mansoni; Schistosoma haematobium; Hematuria; Reagent Strips; Microscopy; Bayes Theorem; Feces; Antigens, Helminth; Urinalysis; Schistosomiasis haematobia; Diagnostic Tests, Routine
PubMed: 38467130
DOI: 10.1016/S2666-5247(23)00377-4 -
Clinical Kidney Journal Feb 2024Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis...
BACKGROUND
Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population.
METHODS
A comprehensive literature search was conducted in the MEDLINE, Embase and Cochrane databases from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycaemic and metabolic parameters, weight, cardiovascular outcomes and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190).
RESULTS
Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12 months (interquartile range 6-23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate [SMD -0.07 ml/min/1.73 m (95% CI -0.64-0.50)] or creatinine [SMD -0.08 mg/dl (95% CI -0.44-0.28)], they were associated with a significant decrease in urine protein:creatinine ratio [SMD -0.47 (95% CI -0.77 to -0.18)] and haemoglobin A1c levels [MD -0.85% (95% CI -1.41 to -0.28)]. Total daily insulin dose, weight and body mass index also decreased significantly. Tacrolimus levels remained stable [MD -0.43 ng/ml (95% CI -0.99 to 0.13)]. Side effects were primarily nausea and vomiting (17.6%), diarrhoea (7.6%) and injection site pain (5.4%).
CONCLUSIONS
GLP-1RAs are effective in reducing proteinuria, improving glycaemic control and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.
PubMed: 38410684
DOI: 10.1093/ckj/sfae018 -
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 -
Medicine Feb 2024In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different studies have reported conflicting results. Therefore, a systematic review and meta-analysis are necessary to assess the efficacy and safety of SML injection for the treatment of DKD.
METHODS
We searched 6 electronic literature databases comparing randomized controlled trials (RCTs) of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), SML injection in combination with ACEIs/ARBs that were conducted from inception until September 5, 2023. Two reviewers extracted data and independently assessed the risk of bias. Using the Cochrane Risk of Bias Tool for Risk Assessment. Mean differences (MD) were combined with random-effects models and the corresponding 95% confidence intervals (CI) were reported. Review Manager 5.4 software was used for meta-analysis. Stata 17.0 software was used for sensitivity analysis and Egger test.
RESULTS
The combined results show that the use of SML injection along with ACEI/ARB led to better outcomes than the use of controls in terms of enhancing recovery: renal function: Serum creatinine (MD = -14.69, 95% CI (-19.38, -10.00)), Blood urea nitrogen (MD = -1.23, 95% CI (-1.72, -0.74)), Urinary β2-microglobulin (MD = -4.58, 95% CI (-7.72, -1.44)); urinary protein: Urinary albumin excretion rate (MD = -45.74, 95% CI (-58.92, -32.56)), Urine albumin-creatinine ratio (MD = -11.93, 95% CI (-13.89, -9.96)), 24-h urine proteinuria (MD = -0.59, 95% CI (-0.86, -0.32)), Urine microalbumin (MD = -13.50, 95% CI (-20.18, -6.83)). Additionally, adjuvant therapy with SML injection enhanced results in blood glucose, blood pressure, lipids, and inflammatory responses, and no significant variations in adverse events were discovered between the 2 groups.
CONCLUSIONS
In patients with DKD, combining SML injection with ACEI/ARB improves renal function, renal proteinuria, hyperglycemia, blood pressure, dyslipidemia, and inflammatory response.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Salvia miltiorrhiza; Proteinuria; Albumins; Angiotensin Receptor Antagonists; Diabetes Mellitus; Pyrazines
PubMed: 38394516
DOI: 10.1097/MD.0000000000035853 -
Cureus Jan 2024Idiopathic membranous nephropathy (IMN) with moderate risk or above was recommended to receive immunosuppressive therapy. We attempted to evaluate the optimal dose of... (Review)
Review
PURPOSE
Idiopathic membranous nephropathy (IMN) with moderate risk or above was recommended to receive immunosuppressive therapy. We attempted to evaluate the optimal dose of glucocorticoid when combined with evidence-proven effective immunosuppressants by network meta-analysis.
METHODS
A systematic review of the literature was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until January 2022. Randomized controlled trials (RCTs) in IMN limited to supportive care, glucocorticoids, cyclophosphamide, chlorambucil, calcineurin inhibitors (CNIs), and rituximab were screened.
RESULTS
Twenty-eight RCTs of 1,830 patients were included. Therapeutic regimens were divided as follows: moderate- to high-dose glucocorticoids plus CNIs (HMSCn), moderate- to high-dose glucocorticoids plus cyclophosphamide (HMSCt), moderate- to high-dose glucocorticoids plus chlorambucil (HMSCh), zero- to low-dose glucocorticoids plus CNIs (LNSCn), zero- to low-dose glucocorticoids plus cyclophosphamide (LNSCt), rituximab alone (R), glucocorticoids alone (SE), and supportive care alone (SP). Compared with SP, HMSCh (risk ratio [RR]: 1.77, 95% confidence interval [CI]: 1, 3.18), HMSCn (RR: 2.5, 95%CI: 1.25, 5.11), HMSCt (RR: 2.15, 95%CI: 1.29, 3.64), LNSCn (RR: 2.16, 95%CI: 1.25, 3.95), and R (RR: 2.07, 95%CI: 1, 4.39) had a higher probability of total remission rate, while HMSCn represented the highest probability depending on the surface under the cumulative ranking area (SUCRA) ranking values. Regarding infection, no significant difference was found between different doses of glucocorticoids plus the same immunosuppressant. HMSCn and HMSCt showed superiority in reducing 24-hour urine total protein compared with HMSCh, LNSCn, SE, and SP, while HMSCn seemed to be the most effective regimen through the ranking of SUCRA value.
CONCLUSION
Moderate- to high-dose glucocorticoids showed superiority in proteinuria remission when combined with CNIs in IMN, with no increasing risk of infection.
PubMed: 38333440
DOI: 10.7759/cureus.51936 -
Systematic Reviews Feb 2024Hydroxyurea is an affordable drug that reduces vaso-occlusive crises and transfusion requirements in sickle cell disease. However, its effectiveness in preventing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hydroxyurea is an affordable drug that reduces vaso-occlusive crises and transfusion requirements in sickle cell disease. However, its effectiveness in preventing chronic organ damage is still unclear. This systematic review and meta-analysis aimed to evaluate the role of hydroxyurea in preventing organ morbidity.
METHOD
We included original articles published in English from 1st January 1990 to 31st January 2023, reporting hydroxyurea therapy and organ damage from PubMed, Google Scholar, Scopus, and CrossRef databases. A total of 45 studies with 4681 sickle cell disease patients were evaluated for organ damage.
RESULTS
Our analysis showed that hydroxyurea intervention significantly lowered transcranial Doppler and tricuspid regurgitant velocity, with a standardized mean difference of - 1.03 (- 1.49; - 0.58); I = 96% and - 1.37 (CI - 2.31, - 0.42); I = 94%, respectively. Moreover, the pooled estimate for albuminuria showed a beneficial effect post-hydroxyurea therapy by reducing the risk of albuminuria by 58% (risk ratio of 0.42 (0.28; 0.63); I = 28%).
CONCLUSION
Our study found that a hydroxyurea dose above 20 mg/kg/day with a mean rise in HbF by 18.46% post-hydroxyurea therapy had a beneficial role in reducing transcranial doppler velocity, tricuspid regurgitant velocity, albuminuria, and splenic abnormality.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023401187.
Topics: Humans; Hydroxyurea; Antisickling Agents; Albuminuria; Anemia, Sickle Cell; Blood Transfusion
PubMed: 38331925
DOI: 10.1186/s13643-024-02461-z -
Frontiers in Endocrinology 2024[This corrects the article DOI: 10.3389/fendo.2023.1168648.].
[This corrects the article DOI: 10.3389/fendo.2023.1168648.].
PubMed: 38318297
DOI: 10.3389/fendo.2024.1357219