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Cancer Treatment Reviews Jul 2023Antibody drug conjugates (ADCs) represent a revolutionary drug class in cancer therapy, combining the precision of targeted therapy with the cytotoxic effects of... (Review)
Review
BACKGROUND
Antibody drug conjugates (ADCs) represent a revolutionary drug class in cancer therapy, combining the precision of targeted therapy with the cytotoxic effects of chemotherapy. Promising activity of novel ADCs, namely Trastuzumab Deruxtecan and Patritumab Deruxtecan, has been observed in hard-to treat molecular subtypes, such as HER2-positive and heavily pretreated EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). However, therapeutic advances are expected in certain subgroups of lung cancer patients, including non-oncogene-addicted NSCLC after failure of current standard of care (e.g., immunotherapy with or without chemotherapy, chemo-antiangiogenic treatment). Trophoblastic Cell Surface Antigen 2 (TROP-2) is a surface transmembrane glycoprotein member of the epithelial cell adhesion molecule (EpCAM) family. TROP-2 represents a promising therapeutic target in refractory non-oncogene-addicted NSCLC.
METHODOLOGY
We performed a systematic literature search of the clinical trials about TROP-2 directed ADCs in NSCLC referenced in the pubmed.gov database, Cochrane Library database and clinicaltrial.gov database.
RESULTS
First-in-humans ADCs targeting TROP-2, namely Sacituzumab Govitecan (SN-38) and Datopotamab Deruxtecan (Dxd), yielded promising activity signals in NSCLC with a manageable safety profile. Most common grade ≥ 3 adverse events (AEs) of Sacituzumab Govitecan included neutropenia (28 %), diarrhea (7 %), nausea (7 %), fatigue (6 %), and febrile neutropenia (4 %). Nausea and stomatitis were the most common all grade AEs with Datopotamab Deruxtecan; dyspnea, amylase increase, hyperglycemia and lymphopenia were reported as grade ≥ 3 AEs in less than 12 % of patients.
CONCLUSION
As more effective strategies are needed for patients with refractory non-oncogene-addicted NSCLC, the design of novel clinical trials with ADCs targeting TROP-2 is encouraged as both a monotherapy or combination strategy with existing agents (e.g., monoclonal antibodies targeting immune checkpoint inhibitors or chemotherapy).
Topics: Humans; Antineoplastic Agents; Camptothecin; Carcinoma, Non-Small-Cell Lung; Immunoconjugates; Irinotecan; Lung Neoplasms
PubMed: 37230055
DOI: 10.1016/j.ctrv.2023.102572 -
The Cochrane Database of Systematic... Apr 2017The treatment of people with acute abdominal pain differs if they have acute pancreatitis. It is important to know the diagnostic accuracy of serum amylase, serum... (Review)
Review
BACKGROUND
The treatment of people with acute abdominal pain differs if they have acute pancreatitis. It is important to know the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis, so that an informed decision can be made as to whether the person with abdominal pain has acute pancreatitis. There is currently no Cochrane review of the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis.
OBJECTIVES
To compare the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase, either alone or in combination, in the diagnosis of acute pancreatitis in people with acute onset of a persistent, severe epigastric pain or diffuse abdominal pain.
SEARCH METHODS
We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase.
SELECTION CRITERIA
We included all studies that evaluated the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis. We excluded case-control studies because these studies are prone to bias. We accepted any of the following reference standards: biopsy, consensus conference definition, radiological features of acute pancreatitis, diagnosis of acute pancreatitis during laparotomy or autopsy, and organ failure. At least two review authors independently searched and screened the references located by the search to identify relevant studies.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the included studies. The thresholds used for the diagnosis of acute pancreatitis varied in the trials, resulting in sparse data for each index test. Because of sparse data, we used -2 log likelihood values to determine which model to use for meta-analysis. We calculated and reported the sensitivity, specificity, post-test probability of a positive and negative index test along with 95% confidence interval (CI) for each cutoff, but have reported only the results of the recommended cutoff of three times normal for serum amylase and serum lipase, and the manufacturer-recommended cutoff of 50 mg/mL for urinary trypsinogen-2 in the abstract.
MAIN RESULTS
Ten studies including 5056 participants met the inclusion criteria for this review and assessed the diagnostic accuracy of the index tests in people presenting to the emergency department with acute abdominal pain. The risk of bias was unclear or high for all of the included studies. The study that contributed approximately two-thirds of the participants included in this review was excluded from the results of the analysis presented below due to major concerns about the participants included in the study. We have presented only the results where at least two studies were included in the analysis.Serum amylase, serum lipase, and urinary trypsinogen-2 at the standard threshold levels of more than three times normal for serum amylase and serum lipase, and a threshold of 50 ng/mL for urinary trypsinogen-2 appear to have similar sensitivities (0.72 (95% CI 0.59 to 0.82); 0.79 (95% CI 0.54 to 0.92); and 0.72 (95% CI 0.56 to 0.84), respectively) and specificities (0.93 (95% CI 0.66 to 0.99); 0.89 (95% CI 0.46 to 0.99); and 0.90 (95% CI 0.85 to 0.93), respectively). At the median prevalence of 22.6% of acute pancreatitis in the studies, out of 100 people with positive test, serum amylase (more than three times normal), serum lipase (more than three times normal), and urinary trypsinogen (more than 50 ng/mL), 74 (95% CI 33 to 94); 68 (95% CI 21 to 94); and 67 (95% CI 57 to 76) people have acute pancreatitis, respectively; out of 100 people with negative test, serum amylase (more than three times normal), serum lipase (more than three times normal), and urinary trypsinogen (more than 50 ng/mL), 8 (95% CI 5 to 12); 7 (95% CI 3 to 15); and 8 (95% CI 5 to 13) people have acute pancreatitis, respectively. We were not able to compare these tests formally because of sparse data.
AUTHORS' CONCLUSIONS
As about a quarter of people with acute pancreatitis fail to be diagnosed as having acute pancreatitis with the evaluated tests, one should have a low threshold to admit the patient and treat them for acute pancreatitis if the symptoms are suggestive of acute pancreatitis, even if these tests are normal. About 1 in 10 patients without acute pancreatitis may be wrongly diagnosed as having acute pancreatitis with these tests, therefore it is important to consider other conditions that require urgent surgical intervention, such as perforated viscus, even if these tests are abnormal.The diagnostic performance of these tests decreases even further with the progression of time, and one should have an even lower threshold to perform additional investigations if the symptoms are suggestive of acute pancreatitis.
Topics: Acute Disease; Amylases; Biomarkers; Diagnostic Errors; Humans; Lipase; Pancreatitis; Trypsin; Trypsinogen
PubMed: 28431198
DOI: 10.1002/14651858.CD012010.pub2 -
World Journal of Microbiology &... Aug 2022With the advent of green chemistry, the use of enzymes in industrial processes serves as an alternative to the conventional chemical catalysts. A high demand for... (Review)
Review
With the advent of green chemistry, the use of enzymes in industrial processes serves as an alternative to the conventional chemical catalysts. A high demand for sustainable processes for catalysis has brought a significant attention to hunt for novel enzymes. Among various hydrolases, the α-amylase has a gamut of biotechnological applications owing to its pivotal role in starch-hydrolysis. Industrial demand requires enzymes with thermostability and to ameliorate this crucial property, various methods such as protein engineering, directed evolution and enzyme immobilisation strategies are devised. Besides the traditional culture-dependent approach, metagenome from uncultured bacteria serves as a bountiful resource for novel genes/biocatalysts. Exploring the extreme-niches metagenome, advancements in protein engineering and biotechnology tools encourage the mining of novel α-amylase and its stable variants to tap its robust biotechnological and industrial potential. This review outlines α-amylase and its genetics, its catalytic domain architecture and mechanism of action, and various molecular methods to ameliorate its production. It aims to impart understanding on mechanisms involved in thermostability of α-amylase, cover strategies to screen novel genes from futile habitats and some molecular methods to ameliorate its properties.
Topics: Enzymes, Immobilized; Metagenome; Protein Engineering; Starch; alpha-Amylases
PubMed: 35999473
DOI: 10.1007/s11274-022-03396-0 -
Sports (Basel, Switzerland) Jul 2023The use of saliva to monitor immune and hormonal responses in training, competitions, and during recovery is an easy and non-invasive alternative means of collecting... (Review)
Review
The use of saliva to monitor immune and hormonal responses in training, competitions, and during recovery is an easy and non-invasive alternative means of collecting samples compared to serum collection. Saliva can provide insight into a number of interesting biomarkers such as cortisol, testosterone, immunoglobulins, alpha-amylase, and melatonin, among others. High-intensity and exhaustive exercises, such as training or competition, provide variations in immune, protein and hormonal markers. An adequate recovery period, calming down, and recovery methods can contribute to a fast normalization of these markers, decreasing illness, as well as the likelihood of overtraining and injuries, but their effectiveness is still inconclusive. The aim of this review was to investigate the evidence of salivary markers in post-exhaustive exercise during the recovery period. This study is a systematic review from three electronic databases with studies from 2011 to 2021 within healthy humans. The search found 213 studies, and after applying the inclusion and exclusion criteria, while excluding duplicated studies, 14 studies were included in this review. The most cited salivary markers were cortisol and testosterone, as well as their ratio, alpha-amylase and IgA. Half of the studies applied a variety of recovery methods that showed controversial results over salivary markers' impact. However, they showed an impact on the markers from the exercise, which was still dependent on exercise intensity, methodology, and duration.
PubMed: 37505624
DOI: 10.3390/sports11070137 -
Diseases of the Esophagus : Official... Feb 2021Esophagectomy is the gold-standard treatment for esophageal cancer; however, postoperative anastomotic leakage remains the primary concern for surgeons. No consensus...
Esophagectomy is the gold-standard treatment for esophageal cancer; however, postoperative anastomotic leakage remains the primary concern for surgeons. No consensus exists on the optimal investigations to predict an anastomotic leak. This systematic review aims to identify a single test or combination of tests with acceptable sensitivity and specificity to identify anastomotic leak after esophagectomy and to formulate a diagnostic algorithm to facilitate surgical decision-making. A systematic review of PubMed and EMBASE databases was undertaken to evaluate diagnostic investigations for anastomotic leak post-esophagectomy. Each study was reviewed and where possible, the sensitivity, specificity, positive predictive value, and negative predictive value were extracted. The review identified 3,204 articles, of which 49 met the inclusion criteria. Investigations most commonly used for diagnosis of anastomotic leak were: C-reactive protein (CRP), oral contrast imaging, computed tomography (CT), pleural drain amylase concentration, and the 'NUn score'. The sensitivity of CRP for detecting anastomotic leak varied from 69.2% to 100%. Oral contrast studies sensitivities varied between 16% and 87.5% and specificity varied from 20% to 100%. Pleural drain amylase sensitivities ranged between 75% and 100% and specificity ranged from 52% to 95.5%. The NUn score sensitivities ranged from 0% to 95% and specificity from 49% to 94.4%. No single investigation was identified to rule out anastomotic leak in asymptomatic patients. However, the authors propose a diagnostic algorithm incorporating CRP, pleural drain amylase concentration, and CT with oral contrast to aid clinicians in predicting anastomotic leak to facilitate safe, timely discharge post-esophagectomy.
Topics: Anastomosis, Surgical; Anastomotic Leak; Esophageal Neoplasms; Esophagectomy; Humans
PubMed: 33565590
DOI: 10.1093/dote/doaa076 -
Frontiers in Immunology 2023Immune checkpoint inhibitor (ICI) combination therapy has changed the treatment landscape for metastatic renal cell carcinoma (mRCC). However, little evidence exists on... (Meta-Analysis)
Meta-Analysis
Severe and fatal adverse events of immune checkpoint inhibitor combination therapy in patients with metastatic renal cell carcinoma: a systematic review and meta-analysis.
INTRODUCTION
Immune checkpoint inhibitor (ICI) combination therapy has changed the treatment landscape for metastatic renal cell carcinoma (mRCC). However, little evidence exists on the treatment-related severe adverse events (SAEs) and fatal adverse events (FAEs) of ICI combination therapy in mRCC.
METHOD
We searched PubMed, Embase, and Cochrane Library databases to evaluate randomized controlled trials (RCTs) of ICI combination therapy versus conventional tyrosine kinase inhibitor (TKI)-targeted therapy in mRCC. Data on SAEs and FAEs were analyzed using revman5.4 software.
RESULTS
Eight RCTs (n=5380) were identified. The analysis showed no differences in SAEs (60.5% vs. 64.5%) and FAEs (1.2% vs. 0.8%) between the ICI and TKI groups (odds ratio [OR], 0.83; 95%CI 0.58-1.19, p=0.300 and OR, 1.54; 95%CI 0.89-2.69, p=0.120, respectively). ICI-combination therapy was associated with less risk of hematotoxicities, including anemia (OR, 0.24, 95%CI 0.15-0.38, p<0.001), neutropenia (OR, 0.07, 95%CI 0.03-0.14, p<0.001), and thrombocytopenia (OR, 0.05, 95%CI 0.02-0.12, p<0.001), but with increased risks of hepatotoxicities (ALT increase [OR, 3.39, 95%CI 2.39-4.81, p<0.001] and AST increase [OR, 2.71, 95%CI 1.81-4.07, p<0.001]), gastrointestinal toxicities (amylase level increase [OR, 2.32, 95%CI 1.33-4.05, p=0.003] and decreased appetite [OR, 1.77, 95%CI 1.08-2.92, p=0.020]), endocrine toxicity (adrenal insufficiency [OR, 11.27, 95%CI 1.55-81.87, p=0.020]) and nephrotoxicity of proteinuria (OR, 2.21, 95%CI 1.06-4.61, p=0.030).
CONCLUSIONS
Compared with TKI, ICI combination therapy has less hematotoxicity in mRCC but more specific hepatotoxicity, gastrointestinal toxicity, endocrine toxicity, and nephrotoxicity, with a similar severe toxicity profile.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023412669.
Topics: Humans; Carcinoma, Renal Cell; Antineoplastic Agents; Immune Checkpoint Inhibitors; Kidney Neoplasms
PubMed: 37404816
DOI: 10.3389/fimmu.2023.1196793 -
Developmental Psychobiology Nov 2022The aim of this systematic review was to better understand whether and to what extent psychosocial stressors are associated with hypothalamic-pituitary-adrenal axis or... (Review)
Review
The aim of this systematic review was to better understand whether and to what extent psychosocial stressors are associated with hypothalamic-pituitary-adrenal axis or autonomic nervous system stress responses in young children (1-6 years of age). Studies were classified by psychosocial stressors from the ecobiodevelopmental model: social and economic resources, maternal mental health, parent-child relationships, and the physical environment. Of the 2388 identified studies, 32 met full inclusion criteria, including over 9107 children. Child physiologic stress responses were measured as hair and urinary cortisol and cortisone, salivary diurnal and reactive cortisol, salivary reactive alpha-amylase, and respiratory sinus arrhythmia. There were 107 identified relations between psychosocial stressors and physiologic stress responses. Nearly two thirds of these relations suggested that children have dysregulated stress responses as either significantly blunted (n = 27) or increased (n = 37); 43 relations were not significant. Children most consistently had significantly dysregulated stress responses if they experienced postnatal maternal depression or anxiety. Some reasons for the mixed findings may be related to characteristics of the child (i.e., moderators) or stressor, how the stress response or psychosocial stressor was measured, unmeasured variables (e.g., caregiving buffering), researcher degrees of freedom, or publication bias.
Topics: Child, Preschool; Humans; Pituitary-Adrenal System; Hypothalamo-Hypophyseal System; Hydrocortisone; Cortisone; Stress, Psychological; alpha-Amylases; Saliva
PubMed: 36282746
DOI: 10.1002/dev.22320 -
Frontiers in Oral Health 2023Some salivary proteins seem to be differently abundant among caries-free (CF) and caries-affected (CA) individuals, but previous results are contradictory precluding... (Review)
Review
OBJECTIVE
Some salivary proteins seem to be differently abundant among caries-free (CF) and caries-affected (CA) individuals, but previous results are contradictory precluding that definitive conclusion be drawn. A pooled analysis of the available evidence may provide more robust data on identifying oral cavity protein patterns among CF and CA individuals. This systematic review and meta-analysis (PROSPERO CRD42021269079) aimed to compare the oral cavity protein abundance among caries-free and caries-affected individuals.
METHODS
This study was conducted following PRISMA guidelines. PubMed, Embase, and Web of Science databases were systematically assessed (up to February 2023) to retrieve clinical studies written in English, German, or in Latin-based languages that compared the oral cavity protein abundance among CF and CA individuals. Data extraction and methodological quality assessment (NIH guidelines) were independently performed by two investigators. Qualitative synthesis was performed from all included studies and meta-analysis was performed using a random-effects model with inverse variance for studies that reported the concentration of proteins or enzymatic activity. Standardized mean difference (SMD) with respective 95% confidence interval (CI) were calculated for each outcome.
RESULTS
A total of 90 studies (two cohort and 88 cross-sectional designs) of more than 6,000 participants were selected for data extraction, being the quality of evidence graded as "fair" for most of them. The oral cavity of CF individuals presented lower total protein concentration [SMD = 0.37 (95% CI: 0.07-0.68; 18 studies)], lower total antioxidant capacity [SMD = 1.29 (95% CI: 0.74-1.85); 17 studies], and lower carbonic anhydrase activity [SMD = 0.83 (95% CI: 0.58-1.09); three studies], whereas CA individuals presented lower carbonic anhydrase concentration [SMD = -0.66 (95% CI: -1.00 to -0.32); three studies], urease [SMD = -0.95 (IC 95%: -1.72 to -0.17); four studies], and arginine deiminase system [SMD = -2.07 (95% CI: -3.53 to -0.62); three studies] activities. Antimicrobial peptides, secretory immunoglobulin-A concentrations and alpha-amylase activity were similar among individuals.
CONCLUSION
Differences on oral cavity protein abundance were observed among CF and CA individuals. These data indicate some protein patterns for the oral health and dental caries conditions. Even when statistically significant, some of the results were not very consistent. Cohort studies need to be conducted to validate these results.
PubMed: 37780687
DOI: 10.3389/froh.2023.1265817 -
ANZ Journal of Surgery Jun 2022Postoperative pancreatic fistula (POPF) remains a significant complication of pancreatic resection with recent evidence showing a strong association between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative pancreatic fistula (POPF) remains a significant complication of pancreatic resection with recent evidence showing a strong association between post-operative pancreatitis and subsequent development of POPF. Incidence and severity of pancreatitis following endoscopic therapy has been effectively reduced with indomethacin prophylaxis, however further agents require evaluation. We present a systematic literature review and meta-analysis of the prophylactic treatment with corticosteroids or n-acetyl cysteine (NAC) of induced pancreatitis in rodent models.
METHODS
A systematic literature search was conducted using Pubmed, Medline, Embase and Cochrane library to identify eligible randomized control trials (RCT) involving animal models that examined NAC or corticosteroids. The primary outcome was the subsequent effect on serum amylase and IL-6 and the histopathological markers of severity such as pancreatic oedema and necrosis.
RESULTS
Four RCTs (n = 178) met inclusion criteria examining NAC and eight RCTs (n = 546) examining corticosteroid agents (dexamethasone, hydrocortisone, methylprednisolone). Prophylactic administration of all corticosteroid agents showed a net effect in favour of reducing markers of severity of pancreatitis. NAC showed a significant reduction in severity of amylase and necrosis.
CONCLUSION
The RCTs examined suggest that prophylactic administration of corticosteroid agents and NAC can reduce the severity of pancreatitis as indicated by histopathologic markers, serum amylase and IL-6 levels.
Topics: Amylases; Animals; Humans; Interleukin-6; Necrosis; Pancreatitis; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 34936178
DOI: 10.1111/ans.17417 -
International Journal of Surgery... Oct 2015This study to evaluate the utility of drain fluid amylase as a predictor of PF in patients undergoing pancreatic surgery based on the International Study Group of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
This study to evaluate the utility of drain fluid amylase as a predictor of PF in patients undergoing pancreatic surgery based on the International Study Group of Pancreatic Fistula definitions of pancreatic fistula.
METHODS
A comprehensive search was carried out using Pubmed (Medline), Embase, Web of science and Cochrane database for clinical trials, which studied DFA as a diagnostic marker for pancreatic fistula after pancreatic surgery. Sensitivity, specificity and the diagnostic odds ratios with 95% confidence interval were calculated for each study. Summary receiver-operating curves were conducted and the area under the curve was evaluated.
RESULTS
A total of 10 studies were included. The pooled sensitivity and specificity of drain fluid amylase Day 1 for the diagnosis of postoperative pancreatic fistula were 81% and 87%, respectively (area under the curve was 0.897, diagnostic odds ratios was 16.83 and 95%CI was 12.66-22.36), the pooled sensitivity and specificity of drain fluid amylase Day 3 for the diagnosis of postoperative pancreatic fistula were 56% and 79%, respectively (area under the curve was 0.668, diagnostic odds ratios was 3.26 and 95%CI was 1.83-5.82) CONCLUSIONS: The drain fluid amylase Day 1, instead of drain fluid amylase Day 3, may be a useful criterion for the early identification of postoperative pancreatic fistula, and a value of drain fluid amylase Day 1 over than 1300 U/L was a risk factor of pancreatic fistula. And the diagnostic accuracy and the proposed cut-off levels of drain fluid amylase Day 1 in predicting the postoperative pancreatic fistula will have to be validated by multicenter prospective studies.
Topics: Amylases; Drainage; Humans; Odds Ratio; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Risk Factors; Sensitivity and Specificity
PubMed: 26211439
DOI: 10.1016/j.ijsu.2015.07.007