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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 -
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 -
International Journal of Surgery... Aug 2023Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimized. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis.
METHODS
Five databases were searched for relevant and original papers published from January 2000 to December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies.
RESULTS
Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30 758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs were determined. Potential triage tests (negative predictive value >90%) were identified for the ruling out of CR-POPF and included postoperative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300 U/l) and in mixed surgical cohorts (2500 U/l), POD3 drain amylase in PD patients (1000-1010 U/l) and drain lipase in mixed surgery groups (180 U/l). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1.
CONCLUSIONS
The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multivariable risk-stratification models and the improvement of pancreatectomy outcomes.
Topics: Humans; Pancreatic Fistula; Pancreas; Pancreatectomy; Pancreaticoduodenectomy; Postoperative Complications; Drainage; Biomarkers; Amylases; Risk Factors
PubMed: 37216227
DOI: 10.1097/JS9.0000000000000482 -
Neuroscience and Biobehavioral Reviews Aug 2023This systematic review and narrative synthesis characterized parents' physiological stress responses to child distress and how parents' physiological and behavioural... (Review)
Review
This systematic review and narrative synthesis characterized parents' physiological stress responses to child distress and how parents' physiological and behavioural responses relate. The review was pre-registered with PROSPERO (#CRD42021252852). In total, 3607 unique records were identified through Medline, Embase, PsycINFO, and CINAHL. Fifty-five studies reported on parents' physiological stress responses during their young child's (0-3 years) distress and were included in the review. Results were synthesized based on the biological outcome and distress context used and risk of bias was evaluated. Most studies examined cortisol or heart rate variability (HRV). Small to moderate decreases in parents' cortisol levels from baseline to post-stressor were reported across studies. Studies of salivary alpha amylase, electrodermal activity, HRV, and other cardiac outcomes reflected weak or inconsistent physiological responses or a paucity of relevant studies. Among the studies that examined associations between parents' physiological and behavioural responses, stronger associations emerged for insensitive parenting behaviours and during dyadic frustration tasks. Risk of bias was a significant limitation across studies and recommendations for future research are discussed.
Topics: Child; Humans; Parenting; Hydrocortisone; Parents; Heart Rate
PubMed: 37196925
DOI: 10.1016/j.neubiorev.2023.105229 -
Critical Reviews in Food Science and... Apr 2023Appraised for being one of the oldest staple nutritive foods mainly in the Arabian Peninsula, the date palm tree ( L.), is a crop native to the subtropical and tropical...
Appraised for being one of the oldest staple nutritive foods mainly in the Arabian Peninsula, the date palm tree ( L.), is a crop native to the subtropical and tropical regions of Southern Asia and Africa. Different parts of the date tree have been extensively studied for their nutritional and therapeutic properties. Despite an array of publications on the date tree, there has been no attempt to compile in a single study the traditional uses, nutritive value, phytochemical profile, the medicinal properties as well as the potential of the different plant parts as a functional food. Therefore, this review endeavors to systematically review the scientific literature to highlight the traditional uses of date fruit and parts around the world, the nutritional profile of several parts and the medicinal properties. A total of 215 studies was retrieved (traditional uses (n = 26), nutritional (n = 52), and medicinal (n = 84)). Scientific articles were further categorized as in vitro (n = 33), in vivo (n = 35), and clinical (n = 16) evidences. Date seeds were found to be effective against and . Aqueous date pollen was used to manage hormonal problems and boost fertility. Palm leaves showed anti-hyperglycemic effects inhibition of α-amylase and α-glucosidase. Unlike previous studies, this study highlighted the functional roles of all the plant parts of the palm tree and provided insights into the various mechanism of action of their bioactive compounds. Although scientific shreds of evidence have been growing over the years, there is still a dearth of studies concerning the clinical validation of the date fruit and other plant parts to provide strong evidence on their medicinal uses. In conclusion, can be regarded as a potent medicinal plant with prophylactic potential and should be further explored to alleviate the burden of both communicable and non-communicable diseases.
PubMed: 37070182
DOI: 10.1080/10408398.2023.2191285 -
European Review For Medical and... Mar 2023Chinese herbal medicine (CHM) has been widely used in the treatment of hyperlipidemic acute pancreatitis (HLAP), but the credibility of the evidence for this practice is... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Chinese herbal medicine (CHM) has been widely used in the treatment of hyperlipidemic acute pancreatitis (HLAP), but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of CHM therapy for HLAP.
MATERIALS AND METHODS
In this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, PubMed, EMBASE, CBM, CNKI, VIP, and Wanfang databases from inception to October 16, 2022, for randomized controlled trials comparing the combination of CHM and Western medicine therapy vs. Western medicine therapy alone in HLAP adults. This study is registered with PROSPERO (No. CRD 42022371052).
RESULTS
A total of 50 eligible studies involving 3,635 patients were assessed in this meta-analysis. Compared with Western medicine therapy, the combination of CHM increased the total effective rate by 19% in HLAP patients [relative risk (RR): 1.19, 95% CI: (1.16, 1.23)]. There were significant differences between the two groups in improving clinical symptoms, promoting serum amylase and triglyceride recovery, reducing mortality [RR: 0.28, 95% CI: (0.14, 0.56)] and complication rates [RR:0.40, 95% CI: (0.31, 0.52)], and shortening the length of hospital stay [MD: -3.96, 95% CI: (-4.76, -3.16)]. Adverse reactions were similar between groups. Findings were robust in the sensitivity analysis.
CONCLUSIONS
The combined CHM treatment was more effective than Western medicine alone in HLAP patients. However, due to the methodological shortcoming of the eligible studies, caution is needed when interpreting these findings.
Topics: Adult; Humans; Drugs, Chinese Herbal; Acute Disease; Pancreatitis; Randomized Controlled Trials as Topic; Phytotherapy
PubMed: 37013744
DOI: 10.26355/eurrev_202303_31760 -
Cureus Feb 2023A lipase/amylase (L/A) ratio of more than three may be a tool for differentiating alcoholic pancreatitis from non-alcoholic pancreatitis. We conducted a systematic... (Review)
Review
A lipase/amylase (L/A) ratio of more than three may be a tool for differentiating alcoholic pancreatitis from non-alcoholic pancreatitis. We conducted a systematic literature review to identify published studies. A thorough data search of various databases was conducted using keywords. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 survey. Data were extracted under the following headings: country, sample size, baseline characteristics, specificity, and sensitivity of the L/A ratio. Studies were analyzed using a bivariate random-effects model, and the sensitivity and specificity of the L/A ratio were pooled separately. Summary receiver operating characteristic (SROC) curves were plotted using the hierarchical method. A total of nine studies with 1,825 patients were identified for inclusion. SROC showed estimates of the area under the curve to be 0.75 (confidence interval (CI) = 0.71-0.79). Forest plots for sensitivity and specificity showed pooled estimates of sensitivity to be 74% (95% CI = 62-83%) while that of specificity was 63% (95% CI = 47-77%). The pooled diagnostic odds ratio was estimated to be 5 (95% CI = 3-9), the pooled positive likelihood ratio was estimated at 2.0, and the pooled negative likelihood ratio was estimated to be 0.41. We concluded that an L/A ratio of more than 3 has moderate accuracy for the diagnosis of alcoholic pancreatitis.
PubMed: 37007426
DOI: 10.7759/cureus.35618 -
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 -
Biological Psychology Feb 2023Growing evidence indicates the presence of racial differences in sympathetic nervous system (SNS) functioning, yet the nature of these differences is unclear and appears... (Review)
Review
Growing evidence indicates the presence of racial differences in sympathetic nervous system (SNS) functioning, yet the nature of these differences is unclear and appears to vary across different indices of SNS activity. Moreover, racial differences among commonly used indices of SNS activity are under-investigated. This systematic review examines racial differences among widely used resting SNS indices, such as electrodermal activity (EDA), pre-ejection period (PEP), and salivary alpha-amylase (sAA). Our review reveals that Black participants have consistently been found to display lower resting EDA compared to White participants. The few studies that have investigated or reported racial differences in PEP and sAA yield mixed findings about whether racial differences exist. We discuss potential reasons for racial differences in SNS activity, such as index-specific factors, lab confounds, psychosocial environmental factors, and their interactions. We outline a framework characterizing possible contributors to racial differences in SNS functioning. Lastly, we highlight the implications of several definitional, analytic, and interpretive issues concerning the treatment of group differences in psychophysiological activity and provide future recommendations.
Topics: Humans; Saliva; Race Factors; Salivary alpha-Amylases; Sympathetic Nervous System; Psychophysiology
PubMed: 36641137
DOI: 10.1016/j.biopsycho.2023.108496 -
International Journal of Molecular... Jan 2023Social anxiety disorder (SAD) is a common psychiatric condition associated with a high risk of psychiatric comorbidity and impaired social/occupational functioning when... (Review)
Review
Social anxiety disorder (SAD) is a common psychiatric condition associated with a high risk of psychiatric comorbidity and impaired social/occupational functioning when not promptly treated. The identification of biological markers may facilitate the diagnostic process, leading to an early and proper treatment. Our aim was to systematically review the available literature about potential biomarkers for SAD. A search in the main online repositories (PubMed, ISI Web of Knowledge, PsychInfo, etc.) was performed. Of the 662 records screened, 61 were included. Results concerning cortisol, neuropeptides and inflammatory/immunological/neurotrophic markers remain inconsistent. Preliminary evidence emerged about the role of chromosome 16 and the endomannosidase gene, as well as of epigenetic factors, in increasing vulnerability to SAD. Neuroimaging findings revealed an altered connectivity of different cerebral areas in SAD patients and amygdala activation under social threat. Some parameters such as salivary alpha amylase levels, changes in antioxidant defenses, increased gaze avoidance and QT dispersion seem to be associated with SAD and may represent promising biomarkers of this condition. However, the preliminary positive correlations have been poorly replicated. Further studies on larger samples and investigating the same biomarkers are needed to identify more specific biological markers for SAD.
Topics: Humans; Phobia, Social; Neuroimaging; Biomarkers; Hydrocortisone; Amygdala; Anxiety
PubMed: 36614278
DOI: 10.3390/ijms24010835