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Pharmaceuticals (Basel, Switzerland) Jun 2023Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor.... (Review)
Review
Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor. Although it is a pleiotropic molecule, curcumin's free form, which is lipophilic, has low bioavailability and is rapidly metabolized, limiting its clinical use. With the advances in techniques for loading curcumin into nanostructures, it is possible to improve its bioavailability and extend its applications. In this review, we gather evidence about the comparison of the pharmacokinetics (biodistribution and bioavailability) between free curcumin (Cur) and nanostructured curcumin (Cur-NPs) and their respective relationships with antitumor efficacy. The search was performed in the following databases: Cochrane, LILACS, Embase, MEDLINE/Pubmed, Clinical Trials, BSV regional portal, ScienceDirect, Scopus, and Web of Science. The selected studies were based on studies that used High-Performance Liquid Chromatography (HPLC) as the pharmacokinetics evaluation method. Of the 345 studies initially pooled, 11 met the inclusion criteria and all included studies classified as high quality. In this search, a variety of nanoparticles used to deliver curcumin (polymeric, copolymeric, nanocrystals, nanovesicles, and nanosuspension) were found. Most Cur-NPs presented negative Zeta potential ranging from -25 mV to 12.7 mV, polydispersion index (PDI) ranging from 0.06 to 0.283, and hydrodynamic diameter ranging from 30.47 to 550.1 nm. Selected studies adopted mainly oral and intravenous administrations. In the pharmacokinetics analysis, samples of plasma, liver, tumor, lung, brain, kidney, and spleen were evaluated. The administration of curcumin, in nanoparticle systems, resulted in a higher level of curcumin in tumors compared to free curcumin, leading to an improved antitumor effect. Thus, the use of nanoparticles can be a promising alternative for curcumin delivery since this improves its bioavailability.
PubMed: 37513855
DOI: 10.3390/ph16070943 -
The Lancet. Gastroenterology &... Sep 2023The diagnosis of clinically significant portal hypertension is crucial for prognosis and treatment guidance in patients with compensated advanced chronic liver disease...
Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a systematic review and individual patient data meta-analysis.
BACKGROUND
The diagnosis of clinically significant portal hypertension is crucial for prognosis and treatment guidance in patients with compensated advanced chronic liver disease (ACLD). Spleen stiffness measurement (SSM) might improve the non-invasive diagnosis of clinically significant portal hypertension, but previous studies have reported heterogeneous SSM cutoffs. We aimed to evaluate the accuracy of SSM and SSM-based algorithms in this setting.
METHODS
In this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from database inception to Dec 31, 2022, for articles, abstracts, and letters, with no restrictions on language. Cross-sectional studies reporting hepatic venous pressure gradient and SSM by different techniques (transient elastography; two-dimensional shear-wave elastography [2D-SWE]; point shear-wave elastography [p-SWE]) in adults (≥18 years) with compensated ACLD were eligible for inclusion. The main outcome was the diagnostic performance of two SSM-based algorithms, with the Baveno VII model as a reference, evaluating sensitivity and specificity, as well as summary negative predictive values (NPVs) and positive predictive values (PPVs). In the Baveno VII model, clinically significant portal hypertension was ruled out if patients had a liver stiffness measurement (LSM) of 15 kPa or less and a platelet count of 150 × 10 platelets per L or higher and ruled in if they had an LSM of greater than 25 kPa. The two SSM-based models combined these same cutoffs with additional criteria. In the Baveno VII-SSM single cutoff model, clinically significant portal hypertension was ruled out if at least two of the following were present: LSM of 15 kPa or less, platelet count of 150 × 10 platelets per L or higher, and SSM of 40 kPa or less; and ruled in if at least two were present: LSM of greater than 25 kPa, platelet count of less than 150 × 10 platelets per L, and SSM of greater than 40 kPa. The Baveno VII-SSM dual cutoff model used the same criteria, but with a cutoff of SSM of less than 21 kPa to rule out, and greater than 50 kPa to rule in, clinically significant portal hypertension. This study is registered with PROSPERO, CRD42019127164.
FINDINGS
Of the 44 records assessed for eligibility, 17 studies (with 1245 patients) were included in the meta-analysis. In the transient elastography cohort (n=600), the Baveno VII algorithm was validated for both ruling out (NPV 100%, 95% CI 64-100; sensitivity 100%, 95% CI 70-100) and ruling in (PPV 95%, 85-98; specificity 94%, 95% CI 87-97) clinically significant portal hypertension, but the proportion of patients with indeterminate results (grey zone) was 48% (95% CI 44-52); 57% (95% CI 52-62) of patients with clinically significant portal hypertension were included in the rule-in zone. The Baveno VII-SSM dual cutoff model had adequate NPV (98%, 95% CI 58-100; sensitivity 100%, 95% CI 91-100) and PPV (93%, 95% CI 84-97; specificity 89%, 95% CI 84-93), with 32% (95% CI 28-36) of patients in the grey zone; 76% (95% CI 72-80) of the patients with clinically significant portal hypertension were in the rule-in zone. The Baveno VII-SSM single cutoff model had a sensitivity of 93% (95% CI 85-97) and a NPV of 85% (95% CI 60-96) for ruling out, and a specificity of 86% (95% CI 80-91) and a PPV of 92% (95% CI 83-95) for ruling in, clinically significant portal hypertension. 88% (95% CI 84-91) of patients with clinically significant portal hypertension were included in the rule-in zone and 9% (95% CI 7-12) of patients were in the grey zone. In the 2D-SWE cohort (n=225), all three algorithms could safely rule in clinically significant portal hypertension with adequate PPV (≥90%), but NPV was inadequate for ruling out clinically significant portal hypertension. Insufficient data were available to evaluate the performance of SSM assessed by p-SWE. Heterogeneity was low (I<25%) for most estimates.
INTERPRETATION
Algorithms combining Baveno VII criteria with SSM showed good performance and reduced the diagnostic grey zone for clinically significant portal hypertension compared with Baveno VII criteria alone. Future studies should evaluate whether SSM-based diagnosis allows for the identification of patients who would benefit from non-selective β-blocker treatment.
FUNDING
None.
PubMed: 37478880
DOI: 10.1016/S2468-1253(23)00150-4 -
Techniques in Coloproctology Dec 2023The aim of the study was to evaluate the ability of magnifying chromoendoscopy (MCE) to correctly differentiate early colorectal cancer (CRC) lesions with massively... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aim of the study was to evaluate the ability of magnifying chromoendoscopy (MCE) to correctly differentiate early colorectal cancer (CRC) lesions with massively invasive submucosal cancer (SMm) from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, slightly invasive submucosal cancer (SMs)).
METHODS
We searched PubMed, Embase, the Cochrane Library from the time of the establishment of each database to 5 April 2023. Stata 15 software was used to perform the meta-analysis for sensitivity, specificity, positive likelihood ratio (LR), and negative LR, diagnostic odds ratio, and 95% CI. A summary receiver-operating characteristic (SROC) curve was constructed, the area under the curve (AUC) was calculated, and the diagnostic value was evaluated. Furthermore, to explore the potential sources of heterogeneity, we used meta-regression to estimate the influencing factors of these studies and their impact on the diagnostic accuracy. MCE was used to evaluate the diagnostic accuracy in differentiating CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs). Subgroup analysis was conducted as well. Deeks' funnel plots were also used to assess publication bias.
RESULTS
A total of 11,387 colorectal lesions were included in 19 articles, including polyp, adenoma, dysplasia, and early cancer (intramucosal cancer, SMs, and SMm). The aggregate sensitivity, specificity, positive LR, negative LR, and diagnostic advantage scores of MCE in the diagnosis of differentiating CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs) were 0.78 (95% CI 0.72-0.83), 0.95 (0.95% CI 0.91-0.97), 15.4 (0.95% CI 8.7-27.4), 0.23 (0.95% CI 0.18-0.30), and 66 (0.95% CI 32-136), respectively. The AUC of the SROC curve was 0.91 (0.95% CI 0.88-0.93). No significant publication bias was found with Deeks' funnel plot. The results showed significant heterogeneity due to the different objects included.
CONCLUSION
MCE can differentiate CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs) with high accuracy and it can guide assessment of invasion depth of SMm in T1 early CRCs to help us select the most appropriate treatment.
Topics: Humans; Colorectal Neoplasms; Endoscopy; Adenoma; Sensitivity and Specificity
PubMed: 37474693
DOI: 10.1007/s10151-023-02833-y -
Clinical Imaging Oct 2023To evaluate the value of four indices of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced (Gd-EOB-DTPA) magnetic resonance as a potential imaging... (Meta-Analysis)
Meta-Analysis Review
AIMS
To evaluate the value of four indices of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced (Gd-EOB-DTPA) magnetic resonance as a potential imaging marker of liver functional reserve.
METHODS
PubMed/Medline, Embase, Cochrane Library, and Web of Science were searched for studies concerning the relationship between Gd-EOB-DTPA-enhanced MRI and liver functional reserve estimated by ICG-R15, Pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated, Meanwhile, Sensitivity and subgroup analyses were performed along with Egger's test for the estimation of publication bias and potential heterogeneity.
RESULTS
14 publications with 1285 patients were included. The pooled r between relative liver enhancement (RLE), reduction rate of T1 relaxation time of the liver (rrT1), liver-to-spleen ratio (LSR), liver-to-muscle ratio (LMR), and ICG-R15 were -0.49 (95% CI, -0.56 to -0.41, p < 0.05), -0.47 (95% CI, -0.57 to -0.36, p < 0.05), -0.45 (95% CI, -0.55 to -0.34, p < 0.05), -0.50 (95% CI, -0.61 to -0.38, p < 0.05). moderate heterogeneity was observed between studies on rrT1, LSR, LMR, and ICG-R15 (p ≤ 0.05), but no significant heterogeneity was observed between RLE and ICG-R15. Further analysis shows that there was a notable heterogeneity between subgroup analysis of LSR and ICG-R15 stratified by years of publication, as well as rrT1 and LMR stratified by total patients and study design, the distribution funnel plots and the results of Egger's test showed no evidence of publication bias.
CONCLUSIONS
RLE, LSR, LMR, and rrT1 all correlated significantly with ICG-R15-estimated hepatic functional reserve. The four indices represent a promising imaging biomarker in the prediction of liver functional reserve.
Topics: Humans; Liver Function Tests; Contrast Media; Liver; Gadolinium DTPA; Magnetic Resonance Imaging; Liver Neoplasms; Retrospective Studies
PubMed: 37437466
DOI: 10.1016/j.clinimag.2023.06.018 -
Reviews in Endocrine & Metabolic... Dec 2023Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all...
Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all cases reported in the last four decades. We also describe one unreported patient. From 28 patients with ectopic insulinoma, 78.6% were female and mean age was 55.7 ± 19.2 years. Hypoglycaemia was the first symptom in 85.7% while 14.3% complained of abdominal pain or genital symptoms. Median tumour diameter was 27.5 [15-52.5] mm and it was localised by CT (73.1%), MRI (88.9%), [Ga]Ga-DOTA-exedin-4 PET/CT (100%), Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC (100%), somatostatin receptor scintigraphy (40%) and endoscopic ultrasound (50%). Ectopic insulinomas were located at duodenum (n = 3), jejunum (n = 2), and one respectively at stomach, liver, appendix, rectum, mesentery, ligament of Treitz, gastrosplenic ligament, hepatoduodenal ligament and splenic hilum. Seven insulinomas were affecting the female reproductive organs: ovary (n = 5), cervix (n = 2) and remaining tumours were at retroperitoneum (n = 3), kidney (n = 2), spleen (n = 1) and pelvis (n = 1). 89.3% underwent surgery (66.7% surgery vs. 33.3% laparoscopy) and 16% underwent an ineffective pancreatectomy. 85.7% had localized disease at diagnosis and 14.3% developed distant metastasis. Median follow-up time was 14.5 [4.5-35.5] months and mortality was reported in 28.6% with median time until death of 60 [5-144] months. In conclusion, ectopic insulinomas are presented as hypoglycaemia with female preponderance. Functional imaging [Ga]Ga-DOTA-exedin-4 PET/CT and Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC have very high sensitivity. Clinicians should be alert to the possibility of extra-pancreatic insulinomas when classic diagnostic tests and intraoperative pancreas exploration failed to locate the tumour.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Gallium Radioisotopes; Hypoglycemia; Insulinoma; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Somatostatin
PubMed: 37434098
DOI: 10.1007/s11154-023-09824-2 -
The Journal of Trauma and Acute Care... Sep 2023Observed variations in the management of pediatric solid organ injuries (SOIs) may be due to difficulty in finding and integrating recommendations from multiple clinical...
BACKGROUND
Observed variations in the management of pediatric solid organ injuries (SOIs) may be due to difficulty in finding and integrating recommendations from multiple clinical practice guidelines (CPGs) with heterogeneous methodological approaches. We aimed to systematically review CPG recommendations for pediatric SOIs.
METHODS
We conducted a systematic review of CPGs including at least one recommendation targeting pediatric SOI populations, using Medical Analysis and Retrieval System Online, Excerpta Medica dataBASE, Web of Science, and websites of clinical organizations. Pairs of reviewers independently assessed eligibility, extracted data, and evaluated the quality of CPGs using the Appraisal of Guidelines Research and Evaluation II tool. We synthesized recommendations from moderate to high-quality CPGs using a recommendations matrix based on Grades of Recommendation, Assessment, Development, and Evaluation criteria.
RESULTS
We identified eight CPGs, including three rated moderate or high quality. Methodological weaknesses included lack of stakeholder involvement beyond surgeons, consideration of applicability (e.g., implementation tools), and clarity around the definition of pediatric populations. Five of the 15 recommendations from moderate to high-quality CPGs were based on moderate quality evidence or were rated as strong; these reflected nonoperative management and angioembolization for renal injuries and required length of stay for liver and spleen injuries.
CONCLUSION
We identified 15 recommendations on pediatric SOI management from 3 moderate or high-quality CPGs, but only one third were based on at least moderate-quality evidence or were rated as strong. Our results prompt the following recommendations for future CPG development or updates: (1) include all types of clinicians involved in the care of pediatric SOIs and patient and family representatives in the process, (2) develop clear definitions of the target population, and (3) provide advice and tools to promote implementation. Results also underline the urgent need for more rigorous research to support strong evidence-based recommendations in this population.
LEVEL OF EVIDENCE
Systematic Review/Meta-analysis; Level III.
Topics: Child; Humans; Wounds and Injuries; Pediatrics; Practice Guidelines as Topic
PubMed: 37272747
DOI: 10.1097/TA.0000000000004015 -
International Journal of Legal Medicine Sep 2023Post-mortem interval (PMI) is the cornerstone of the forensic field to investigate. The examination technique by seeing the changes in the body such as algor mortis,... (Review)
Review
BACKGROUND
Post-mortem interval (PMI) is the cornerstone of the forensic field to investigate. The examination technique by seeing the changes in the body such as algor mortis, rigor mortis, and livor mortis is a traditional technique in which accuracy is influenced by many factors. A biomolecular technique that uses microRNA (miRNA) biomarkers is developing because miRNA has good stability than other RNA, so it meets the requirements to be used for PMI estimation.
METHOD
Following the PRISMA guidelines, journals were taken from 5 databases: Scopus, Science Direct, PubMed, Embase, and Springer. The review was carried out by two people. Inclusion criteria in this review are original research, published in the last 10 years, discussing miRNA as a biomarker for PMI estimation, and free full access. While exclusion criteria are not original research and not using English.
RESULT
Eighteen journals were reviewed in this study. The study was conducted using test animals (rats) and human samples with tissue sources taken from the liver, skeletal muscle, blood, bone, heart, skin, saliva, semen, brain, lung, vitreous humor, spleen, and kidney. miRNA expression levels after death showed different results based on miRNA target, tissue source, and others.
DISCUSSION
The results of each study are different due to the use of different types of miRNA targets and tissue sources. miRNA has great potential to estimate PMI in forensic science, but it is necessary to control the influencing factors to obtain an accurate conclusion.
Topics: Humans; Animals; Rats; MicroRNAs; Autopsy; Postmortem Changes; Forensic Medicine; Forensic Sciences; Biomarkers
PubMed: 37253884
DOI: 10.1007/s00414-023-03015-z -
Swiss Medical Weekly May 2023Epstein-Barr virus (EBV), also known as human herpesvirus 4, is one of the most common pathogenic viruses in humans. EBV mononucleosis always involves the spleen and as...
BACKGROUND
Epstein-Barr virus (EBV), also known as human herpesvirus 4, is one of the most common pathogenic viruses in humans. EBV mononucleosis always involves the spleen and as such it predisposes to splenic rupture, often without a trauma, and splenic infarction. Nowadays the goal of management is to preserve the spleen, thereby eliminating the risk of post-splenectomy infections.
METHODS
To characterise these complications and their management, we performed a systematic review (PROSPERO CRD42022370268) following PRISMA guidelines in three databases: Excerpta Medica, the United States National Library of Medicine, and Web of Science. Articles listed in Google Scholar were also considered. Eligible articles were those describing splenic rupture or infarction in subjects with Epstein-Barr virus mononucleosis.
RESULTS
In the literature, we found 171 articles published since 1970, documenting 186 cases with splenic rupture and 29 with infarction. Both conditions predominantly occurred in males, 60% and 70% respectively. Splenic rupture was preceded by a trauma in 17 (9.1%) cases. Approximately 80% (n = 139) of cases occurred within three weeks of the onset of mononucleosis symptoms. A correlation was found between the World Society of Emergency Surgery splenic rupture score, which was retrospectively calculated, and surgical management: splenectomy in 84% (n = 44) of cases with a severe score and in 58% (n = 70) of cases with a moderate or minor score (p = 0.001). The mortality rate of splenic rupture was 4.8% (n = 9). In splenic infarction, an underlying haematological condition was observed in 21% (n = 6) of cases. The treatment of splenic infarction was always conservative without any fatal outcomes.
CONCLUSIONS
Similarly to traumatic splenic rupture, splenic preservation is increasingly common in the management of mononucleosis-associated cases as well. This complication is still occasionally fatal. Splenic infarction often occurs in subjects with a pre-existing haematological condition.
Topics: United States; Male; Humans; Infectious Mononucleosis; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Splenic Infarction; Retrospective Studies; Rupture, Spontaneous; Splenic Rupture
PubMed: 37245117
DOI: 10.57187/smw.2023.40081 -
Clinical Nuclear Medicine Jun 2023The interactions between the administration of cold somatostatin analogs (cSAs) and their radiolabeled counterpart remain unclear, and discontinuation before imaging is...
PURPOSE
The interactions between the administration of cold somatostatin analogs (cSAs) and their radiolabeled counterpart remain unclear, and discontinuation before imaging is still advised as a precaution. The aim of this systematic review is to evaluate the consequences of cSA administration on tumoral and surrounding healthy organs' uptake at somatostatin receptor (SSTR) imaging with SPECT or PET.
METHODS
After registration of the study on Prospero (CRD42022360260), an electronic search of PubMed and Scopus databases was performed. Inclusion criteria were as follows: human patients referred for SSTR imaging for oncological purposes; at least 1 examination performed either before cSA administration or after a long-enough withdrawal of cSA treatment; at least 1 examination was performed under cSA treatment. Included articles were independently appraised by 2 authors using the standardized protocol provided by the Quality Assessment of Diagnostic Accuracy Studies. Discrepancies were solved by consensus.
RESULTS
A total of 12 articles were included, 4 using 111In-pentetreotide and 8 using 68Ga-DOTA peptides. Administration of cSAs consistently resulted in decreased spleen and liver uptake (from 6.9% to 80% for spleen, 10% to 60% for liver) and increased tumor-to-background or tumor-to-healthy organ ratios. After cSA treatment, tumor uptake alone was unchanged or moderately decreased. Similar results were noted whether patient was octreotide-naive.
CONCLUSION
Impairment in SSTR imaging quality after cSA administration has not been demonstrated. On the contrary, the administration of cSAs seems to improve the contrast between tumoral lesions and the surroundings.
Topics: Humans; Receptors, Somatostatin; Somatostatin; Octreotide; Tomography, Emission-Computed, Single-Photon; Neoplasms; Neuroendocrine Tumors
PubMed: 37133509
DOI: 10.1097/RLU.0000000000004670 -
Abdominal Radiology (New York) Jul 2023Porto-sinusoidal vascular disorder (PSVD) is one of the common causes of portal hypertension and has overlapping features with early cirrhosis. The differentiation of...
BACKGROUND
Porto-sinusoidal vascular disorder (PSVD) is one of the common causes of portal hypertension and has overlapping features with early cirrhosis. The differentiation of PSVD from cirrhosis requires a liver biopsy, which is invasive and has potential complications. This systematic review aimed at summarizing the current evidence on the performance of noninvasive modalities for differentiating PSVD from cirrhosis.
METHODS
A comprehensive search of electronic databases of MEDLINE, Embase, and Scopus was conducted from 2000 to October 2022 for the studies comparing the elastographic and radiological features of PSVD and cirrhosis, using liver biopsy as the gold standard.
RESULTS
A total of 12 studies were included in the systematic review. Transient elastography (TE) as a modality was studied in five studies, MR elastography (MRE) in two, contrast CT in two, Contrast CT and MRI in two, and ARFI in only one. Both TE and MRE showed a significantly lower liver stiffness measurement and a higher splenic stiffness measurement with a higher SSM/LSM ratio with PSVD, compared to cirrhosis. Among the radiological features, focal nodular hyperplasia-like lesions, portal vein abnormalities (intrahepatic and extrahepatic), and a larger spleen size favored a diagnosis of PSVD. In contrast, surface nodularity and atrophy of segment IV with a segment I hypertrophy favored a diagnosis of cirrhosis.
CONCLUSION
Elastography and cross-sectional imaging can help differentiate PSVD from early cirrhosis with good accuracy. Further studies are required to assess the diagnostic role of a combination of both modalities.
Topics: Idiopathic Noncirrhotic Portal Hypertension; Liver Cirrhosis; Diagnosis, Differential; Humans; Elasticity Imaging Techniques; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 37119294
DOI: 10.1007/s00261-023-03927-9