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Frontiers in Immunology 2023This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.
METHODS
We conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic review and meta-analysis.
RESULTS
59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy.
CONCLUSION
Our study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier 345350.
Topics: Humans; Immune Checkpoint Inhibitors; Pancreatitis; Neoplasms; Amylases; Lipase
PubMed: 37359551
DOI: 10.3389/fimmu.2023.1166299 -
Molecules (Basel, Switzerland) Jan 2022(1) Background: Benth. is a traditional medicine used in the treatment of diabetes and chronic renal failure in southern China, Malaysia, and Thailand. Diabetes is a...
(1) Background: Benth. is a traditional medicine used in the treatment of diabetes and chronic renal failure in southern China, Malaysia, and Thailand. Diabetes is a chronic metabolic disease and the number of diabetic patients in the world is increasing. This review aimed to systematically review the effects of in the treatment of diabetes and its complications and the pharmacodynamic material basis. (2) Methods: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the databases ScienceDirect, PubMed, and Web of Science. (3) Results: Thirty-one articles related to and diabetes were included. The mechanisms of in the treatment of diabetes and its complications mainly included inhibiting α-amylase and α-glucosidase activities, antioxidant and anti-inflammatory activities, regulating lipid metabolism, promoting insulin secretion, ameliorating insulin resistance, increasing glucose uptake, promoting glycolysis, inhibiting gluconeogenesis, promoting glucagon-likepeptide-1 (GLP-1) secretion and antiglycation activity. Phenolic acids, flavonoids and triterpenoids might be the main components for hypoglycemia effects in . (4) Conclusion: could be an antidiabetic agent to treat diabetes and its complications. However, it needs further study on a pharmacodynamic substance basis and the mechanisms of effective constituents.
Topics: Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Resistance; Lipid Metabolism; Medicine, East Asian Traditional; Orthosiphon; Plant Extracts; Plants, Medicinal
PubMed: 35056765
DOI: 10.3390/molecules27020444 -
Immunopharmacology and Immunotoxicology Dec 2023Immune checkpoint inhibitors have advanced immunotherapy for melanoma patients. This study evaluates efficacy and safety of ipilimumab and nivolumab combination (IN) for... (Meta-Analysis)
Meta-Analysis
CONTEXT
Immune checkpoint inhibitors have advanced immunotherapy for melanoma patients. This study evaluates efficacy and safety of ipilimumab and nivolumab combination (IN) for melanoma brain metastases (MBM) patients.
MATERIALS AND METHODS
Literature search was conducted in electronic databases and studies were included if they reported efficacy and safety of IN in MBM patients or prognostic information related to brain metastases. Outcomes evaluated were objective response rate (ORR), complete remission/stable disease/progressive disease rates, progression-free survival (PFS), overall survival (OS), incidence rates of adverse events, and hazard ratios of disease progression or mortality between IN-treated patients with and without brain metastasis.
RESULTS
Intracranial ORR was higher in IN-treated MBM patients than with control therapies (nivolumab or ipilimumab plus fotemustine). IN treatment led to longer PFS and OS in than control treatments. Five-year OS of IN-treated MBM patients was up to 51% compared to 34% for nivolumab. Outcomes were better for treatment naïve and asymptomatic patients. Whereas many studies reported significantly higher mortality or progression risk with IN treatment in MBM patients compared to non-MBM melanoma patients, many others did not find this risk significant. Incidence of grade 3/4 adverse events in IN-treated MBM patients was: diarrhea or colitis (16%), hepatitis (15%), rash (8%), increased alanine transaminase (8%), increased aspartate aminotransferase (7%), increased lipase (6%), increased amylase (4%), fatigue (3%), hypophysitis (2%), pneumonitis (2%), headache (2%), nausea or vomiting (1%), and neutropenia (1%).
CONCLUSION
IN is an efficacious and safer treatment option for MBM patients, especially for asymptomatic and treatment naïve patients.
Topics: Humans; Nivolumab; Ipilimumab; Melanoma; Brain Neoplasms; Progression-Free Survival; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37228242
DOI: 10.1080/08923973.2023.2215403 -
Diabetes Research and Clinical Practice Jan 2020While there is plentiful evidence on elevated serum levels of amylase, lipase, and trypsin in acute illness, low serum levels of these digestive enzymes have been... (Meta-Analysis)
Meta-Analysis
AIMS
While there is plentiful evidence on elevated serum levels of amylase, lipase, and trypsin in acute illness, low serum levels of these digestive enzymes have been studied infrequently. The aim was to systematically review published studies on the relationship between low serum levels of amylase, lipase, or trypsin and metabolic disorders.
METHODS
The search was conducted in MEDLINE and Scopus databases. Studies in humans were included if they reported on the association between serum levels of amylase, lipase, or trypsin within normal range and metabolic disorders. Random-effects meta-analysis was conducted.
RESULTS
A total of 20 studies encompassing 20,916 participants were included. Compared with healthy individuals, individuals with type 2 diabetes mellitus (mean difference = -5.3; p < 0.001), metabolic syndrome (mean difference = -5.1; p < 0.001), and overweight/obesity (mean difference = -0.8; p = 0.02) had significantly lower serum levels of amylase. Both individuals with type 1 diabetes mellitus (mean difference = -1.8; p < 0.001) and type 2 diabetes mellitus (mean difference = -0.8; p < 0.001) had significantly lower serum levels of lipase compared with healthy individuals. Data on serum trypsin were not suitable for meta-analysis. In the pooled analysis, individuals with type 2 diabetes mellitus had 3.1-times lower serum levels of amylase, 2.9-times lower serum levels of lipase, and 2.5-times lower serum levels of trypsin levels than the upper limits of normal for the three digestive enzymes.
CONCLUSION
Low serum levels of amylase and lipase are significantly associated with type 2 diabetes mellitus, type 1 diabetes mellitus, excess adiposity, and metabolic syndrome. The role of digestive enzymes in the pathogenesis of metabolic disorders warrants further investigations.
Topics: Amylases; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Lipase; Metabolic Diseases; Metabolic Syndrome; Obesity; Overweight; Trypsin
PubMed: 31811884
DOI: 10.1016/j.diabres.2019.107974 -
Journal of Clinical Pathology Aug 2016Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities.
METHODS
PubMed database was used to identify relevant literature. Primary end point was comparison of positive immunostaining of the biomarkers in chRCC and RO, with extracted data used to calculate OR and 95% CI and statistical I(2) test of heterogeneity for multiple studies.
RESULTS
One hundred and nine manuscripts were available for review. Data extracted were subjected to quantitative meta-analysis. Ten most effective biomarkers (OR of chRCC/RO and CI) are: amylase α1A (n=129, OR=0.001, 95% CI 0.0001 to 0.019); Wnt-5a (n=38, OR=0.0076, 95% CI 0.0004 to 0.015); FXYD2 (n=57, OR=130, 95% CI 14.2 to 1192.3); ankyrin-repeated protein with a proline-rich region (ARPP) (n=25, OR=0.0054, 95% CI 0.0002 to 0.12); cluster of differentiation 63 (CD63) (n=62, diffuse (chRCC) vs apical/polar (RO) stain pattern); transforming growth factor β 1 (TGFβ1) (n=34, membranous (chRCC) vs cytoplasmic (RO)); cytokeratin 7 (CK7) (11 studies, n=448, pooled OR=44.22, 95% CI 22.52 to 86.64, I(2)=15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I(2)=0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I(2)=70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I(2)=0%).
CONCLUSIONS
We recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.
Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Neoplasms
PubMed: 26951082
DOI: 10.1136/jclinpath-2015-203585 -
Oral Diseases Oct 2023The objective of this systematic review was to evaluate which salivary biomarkers are altered in patients with burning mouth syndrome (BMS) compared to a control group... (Meta-Analysis)
Meta-Analysis Review
The objective of this systematic review was to evaluate which salivary biomarkers are altered in patients with burning mouth syndrome (BMS) compared to a control group (CG). A comprehensive literature search was conducted in four databases. Case-control studies evaluating salivary biomarkers in BMS patients were included. Risk of bias was assessed using the Newcastle-Ottawa tool. RevMan was used for meta-analysis. Seventeen studies were selected. The included studies collected 54 different biomarkers. Of these biomarkers, only three (cortisol, α-amylase, and dehydroepiandrosterone) were analyzed in three or more studies. Dehydroepiandrosterone obtained contradictory results among the studies. However, cortisol and α-amylase levels were found to be higher in BMS patients. Cortisol was the only biomarker which could be included for meta-analysis. Cortisol levels were significantly higher in the BMS group compared to the CG (Mean Difference = 0.39; 95% CI [0.14-0.65]; p = 0.003). In conclusion, different studies investigated salivary biomarkers in patients with BMS compared to a CG, with controversial results. Meta-analysis, confirmed by trial-sequential analysis, showed how cortisol levels were significantly higher in BMS. Cortisol emerges as an interesting salivary biomarker in BMS, but future properly designed studies are needed to evaluate its role in diagnosis and/or response to treatment.
Topics: Humans; Saliva; Burning Mouth Syndrome; Hydrocortisone; Biomarkers; alpha-Amylases; Dehydroepiandrosterone
PubMed: 36135356
DOI: 10.1111/odi.14390 -
Current Issues in Molecular Biology May 2024The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the... (Review)
Review
The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries ( < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.
PubMed: 38785526
DOI: 10.3390/cimb46050258 -
Endoscopy International Open Jul 2022Post-ERCP pancreatitis (PEP) is the most common complication attributed to the procedure, its incidence being approximately 9.7 %. Numerous studies have evaluated the...
Post-ERCP pancreatitis (PEP) is the most common complication attributed to the procedure, its incidence being approximately 9.7 %. Numerous studies have evaluated the predictive efficacy of post-procedure serum amylase and lipase levels but with varied procedure-to-test time intervals and cut-off values. The aim of this meta-analysis was to present pooled data from available studies to compare the predictive accuracies of serum amylase and lipase for PEP. A total of 18 studies were identified after a comprehensive search of various databases until June 2021 that reported the use of pancreatic enzymes for PEP. The sample size consisted of 11,790 ERCPs, of which PEP occurred in 764 (6.48 %). Subgroups for serum lipase and amylase were created based on the cut-off used for diagnosing PEP, and meta-analysis was done for each subgroup. Results showed that serum lipase more than three to four times the upper limit of normal (ULN) performed within 2 to 4 hours of ERCP had the highest pooled sensitivity (92 %) for PEP. Amylase level more than five to six times the ULN was the most specific serum marker with a pooled specificity of 93 %. Our analysis indicates that a lipase level less than three times the ULN within 2 to 4 hours of ERCP can be used as a good predictor to rule out PEP when used as an adjunct to patient clinical presentation. Multicenter randomized controlled trials using lipase and amylase are warranted to further evaluate their PEP predictive accuracy, especially in high-risk patients.
PubMed: 35845027
DOI: 10.1055/a-1793-9508 -
Natural Products and Bioprospecting Jan 2024Diabetes mellitus remains a major global health issue, and great attention is directed at natural therapeutics. This systematic review aimed to assess the potential of... (Review)
Review
Diabetes mellitus remains a major global health issue, and great attention is directed at natural therapeutics. This systematic review aimed to assess the potential of flavonoids as antidiabetic agents by investigating their inhibitory effects on α-glucosidase and α-amylase, two key enzymes involved in starch digestion. Six scientific databases (PubMed, Virtual Health Library, EMBASE, SCOPUS, Web of Science, and WHO Global Index Medicus) were searched until August 21, 2022, for in vitro studies reporting IC values of purified flavonoids on α-amylase and α-glucosidase, along with corresponding data for acarbose as a positive control. A total of 339 eligible articles were analyzed, resulting in the retrieval of 1643 flavonoid structures. These structures were rigorously standardized and curated, yielding 974 unique compounds, among which 177 flavonoids exhibited inhibition of both α-glucosidase and α-amylase are presented. Quality assessment utilizing a modified CONSORT checklist and structure-activity relationship (SAR) analysis were performed, revealing crucial features for the simultaneous inhibition of flavonoids against both enzymes. Moreover, the review also addressed several limitations in the current research landscape and proposed potential solutions. The curated datasets are available online at https://github.com/MedChemUMP/FDIGA .
PubMed: 38185713
DOI: 10.1007/s13659-023-00424-w -
Nutrition Research (New York, N.Y.) Mar 2023Mango has long been an attractive source of nutrition and pharmacological therapeutics. The mango plant (Mangifera indica L.) contains bioactive compounds that may have... (Review)
Review
Mango has long been an attractive source of nutrition and pharmacological therapeutics. The mango plant (Mangifera indica L.) contains bioactive compounds that may have antidiabetic properties. This systematic review investigated the evidence for antidiabetic properties of the different parts of the mango plant in managing type 2 diabetes mellitus in animal models and humans. The electronic databases PubMed, FSTA, Web of Science, CINAHL, MEDLINE, and Cochrane Library were systematically searched to identify articles with clear objectives and methodologies available in the English language with publication date limits up to December 2020. Twenty-eight of 1001 animal and human studies met the inclusion criteria that investigated antidiabetic properties of mango from leaf (31%), flesh (38%), seed-kernel (7%), peel (14%), stem-bark (7%), and by-product (3%). Results support the glucose-lowering properties of mango in both animals and human. Proposed antidiabetic mechanisms of action include inhibition of α-amylase and α-glucosidase, improved antioxidant status, improved insulin sensitivity, facilitated glucose uptake, and gene regulation of glucose transporter type 4, insulin receptor substrate 1, and phosphoinositide 3-kinase. The animal and randomized control trial findings suggest that mango may be beneficial as an antidiabetic agent. Although these studies hold promise, additional observational studies and randomized control trials are required because human studies are significantly fewer in number, use mango flesh almost exclusively, and had modest blood glucose effects. Additional research gaps include identifying the mechanisms of action for the different components of the mango plant.
Topics: Animals; Humans; Mangifera; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Plant Extracts; Phosphatidylinositol 3-Kinases; Fruit; Models, Animal
PubMed: 36841190
DOI: 10.1016/j.nutres.2023.01.003