-
Asian Pacific Journal of Cancer... Jun 2021In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with...
Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) Immunohistochemistry in Pheochromocytoma, Head and Neck Paraganglioma, Thoraco-Abdomino-Pelvic Paragangliomas: Is It a Good Idea to Use in Routine Work?
BACKGROUND
In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with immunohistochemistry; compare with Pheochromacytoma of the Adrenal Gland Scaled Score (PASS) classification and analyse the differences between pheochromocytoma (Pheo), head-neck paragangliomas (HNPGL) and thoraco-abdominal-pelvic paraganglioma (TAPPGL) sub-groups.
METHODS
A total 114 PPGL cases (73 HNPGL, 15 TAPPGL and 27 Pheo belonging to 112 cases) are included. Immunohistochemically, SDHB and Ki-67 are investigated and malignancy risks are determined by PASS classification. Results are assessed statistically with chi-square test and p <0,01 is considered significant.
RESULTS
SDHB mutations are observed in 20 of 114 (17.54 %) PPGL cases, 3 (11,12%) of which is Pheo, 12 (16,44) is HNPGL, and 5 (35,71%) is TAPPGL (P <0,02). While 15/82 (18,29%) cases with SDHB mutations do not have a malignancy potential according to PASS classification, 5/32 (15,63%) cases has (p=0,73). TAPPGL, HNPGL and Pheo sub-groups have a significant difference between SDHB expression (p <0,02), malignancy potential according to PASS classification (p <0,0001) and Ki-67 proliferation index (p <0,0001).
CONCLUSION
To identify patients for molecular pathological examination, routine application of SDHB immunohistochemistry to PPGL tumors are suggested especially in HNPGLs.
Topics: Head and Neck Neoplasms; Humans; Immunohistochemistry; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase; Thoracic Neoplasms
PubMed: 34181326
DOI: 10.31557/APJCP.2021.22.6.1721 -
Frontiers in Nutrition 2020Interactions are occurring in the course of liberation, absorption, distribution, metabolism, and excretion of active ingredients, or at the target receptors. They are...
Interactions are occurring in the course of liberation, absorption, distribution, metabolism, and excretion of active ingredients, or at the target receptors. They are causing therapy failures and undesirable events. Forty-seven of fifty-seven human hepatic isoenzymes are specific and relevant in hormone and vitamin metabolism and biosynthesis. Aromatase (syn. CYP19A1) is one of the specific CYP450 isoenzymes so far not elucidated in detail. As aromatase-inhibiting phytochemicals are currently recommended for breast cancer prevention and as add-on accompanying aromatase-inhibitor pharmacotherapy, it was the aim of this literature review to assess whether a common interpretation on genetic and -omics basis could be found. Articles retrieved showed that traditional antioxidation diet is one of the most approved explanations of inhibition of aromatase by phytonutrients of flavonoid derivatives. Flavonoids compete for the oxygen provided by the heme moiety of aromatase in the course of aromatase-catalyzed conversion of steroid precursors to estrogens. Flavonoids are therefore promoted for breast cancer prevention. A further explanation of flavonoids' mechanism of action proposed was related to enzymatic histone deacetylation. By keeping DNA-structure wide through a high acetylation degree, acetylated histones favor transcription and replication. This mechanism corresponds to a procedure of switching genes on. Inhibiting acetylation and therefore switching genes off might be an important regulation of repressing cancer genes. Aromatase expression depends on the genotype and phenotype of a person. Aromatase itself depends on the expression of the heme moiety encoded in the genotype. Biosynthesis of porphyrins in turn depends on the substrates succinate and glycine, as well as on a series of further enzymes, with ALA synthetase as the rate-limiting step. The effect of the heme moiety as prosthetic group of aromatase further depends on the absorption of iron as a function of pH and redox state. To assess the function of aromatase precisely, multiple underlying biochemical pathways need to be evaluated. As a conclusion, the genetic regulation of metabolism is a complex procedure affecting multiple pathways. To understand a metabolic step, multiple underlying individually performing reactions need to be considered if personalized (nutritional) medicine should bring an advantage for a patient. Nutrition sciences need to consider the genome of an individual to truly find answers to nutrition-derived non-communicable diseases. With current GWAS (genome-wide association study) approaches, inherited errors of metabolism are identified and ideally treated effectively. It is much more difficult to get a precise genetic profile for non-communicable diseases stemming from multifactorial causes. Polygenic risks evaluation is feasible but diagnostic tools are not yet available in a desired extent. Neither flavonoid researchers nor providers of genetic testing kits are going into the details needed for a truly personalized nutritional medicine. The next step with profiling the exome and then the whole genome is on the threshold of becoming routine diagnosis and of bringing the desired details.
PubMed: 32328497
DOI: 10.3389/fnut.2020.00037 -
Anaesthesia Apr 2019Butyrylcholinesterase deficiency prolongs the effects of the drugs it degrades; succinylcholine and mivacurium. Existing literature on butyrylcholinesterase deficiency...
Butyrylcholinesterase deficiency prolongs the effects of the drugs it degrades; succinylcholine and mivacurium. Existing literature on butyrylcholinesterase deficiency is dominated by genetic and biochemical studies. We searched MEDLINE, Embase, Web of Science and Biosis to systematically review the causes and clinical consequences of butyrylcholinesterase deficiency. We considered outcomes clinically relevant if neuromuscular blockade, induced by succinylcholine or mivacurium, was assessed using clinical criteria or neuromuscular monitoring. We included 66 studies: 25 randomised controlled trials; 13 clinically controlled trials; 26 prospective observational studies; 1 retrospective study; and 1 qualitative study. Data heterogeneity precluded quantitative synthesis. Studies described genetic, physiological, acquired or pharmacologically induced causes of butyrylcholinesterase deficiency. The prolongation of neuromuscular blockade by butyrylcholinesterase deficiency was most pronounced with homozygosity of a genetic variant, but other more common factors included increasing age, pregnancy, severe liver disease, burn injuries and drug interactions.
Topics: Anesthesia; Apnea; Butyrylcholinesterase; Humans; Metabolism, Inborn Errors; Mivacurium; Neuromuscular Blockade; Neuromuscular Monitoring; Succinylcholine
PubMed: 30600548
DOI: 10.1111/anae.14545 -
Scientific Reports Oct 2022To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in... (Meta-Analysis)
Meta-Analysis
Efficacy, according to urodynamics, of OnabotulinumtoxinA compared with antimuscarinic drugs, for neurogenic detrusor overactivity: a systematic review and network meta-analysis.
To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in neurogenic detrusor overactivity (NDO). We conducted a literature search of EMBASE and PubMed, with the language limited to English. In the analysis, all of the published randomized trials of OnabotulinumtoxinA or antimuscarinic drugs used to treat NDO were found and the results were finally obtained through Bayesian model analysis. A total of 12 RCTs and 2208 patients were included. OnabotulinumtoxinA 300U was superior to other drugs in terms of MCC, volume at IDC, and Pdet endpoints. OnabotulinumtoxinA 200U was more effective on the urodynamic endpoint of BC than other drugs or doses of OnabotulinumtoxinA. According to the MCC urodynamic results, oxybutynin, solifenacin 10 mg, and tolterodine 4 mg also had positive effects. OnabotulinumtoxinA 300U, 200U and 100U were better in improving the urodynamic results of NDO, and the current evidence also shows that selective injection of onabotulinumtoxinA can effectively improve the urodynamic results.
Topics: Humans; Botulinum Toxins, Type A; Urodynamics; Muscarinic Antagonists; Urinary Bladder, Neurogenic; Solifenacin Succinate; Network Meta-Analysis; Tolterodine Tartrate; Bayes Theorem; Treatment Outcome; Urinary Bladder, Overactive
PubMed: 36289427
DOI: 10.1038/s41598-022-22765-1 -
BMC Anesthesiology Mar 2020The evidence base for the widely accepted standard regimen of succinylcholine for rapid sequence induction (1.0 mg kg) remains unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The evidence base for the widely accepted standard regimen of succinylcholine for rapid sequence induction (1.0 mg kg) remains unclear.
METHODS
We performed a systematic review and meta-analysis of randomized trials comparing any succinylcholine regimen with the standard regimen (1.0 mg kg) and reporting on intubating conditions and/or apnoea times. Results were expressed as absolute risk differences (ARD) for dichotomous data and mean differences (MD) for continuous data.
RESULTS
We retrieved six trials with relevant data of 864 patients (ASA 1 or 2, aged 18-65 years, body mass index < 30 kg m). Four regimens (0.3, 0.4, 0.5, 0.6 mg kg) were compared with 1.0 mg kg in at least three trials each, and three (0.8, 1.5, 2 mg kg) in one each. With 0.3 to 0.5 mg kg, the likelihood of excellent intubating conditions was significantly decreased (ARD - 22% to - 67%). With 0.3 and 0.4 mg kg, but not with 0.5, 0.6, 0.8, 1.5 and 2.0 mg kg, the likelihood of unacceptable intubating conditions was significantly increased (ARD + 22% and + 32%, respectively). With 2.0 mg kg, but not with 0.8 or 1.5 mg kg, the likelihood of excellent intubating conditions was significantly increased (ARD + 23%). Apnoea times were significantly shorter with regimens ≤0.8 mg kg (MD - 1.0 to - 3.4 min) but were not reported with 1.5 or 2.0 mg kg.
CONCLUSIONS
With succinylcholine regimens ≤0.5 mg kg, excellent intubating conditions are less likely and apnoea times are shorter, compared with 1 mg kg. With 0.3 and 0.4 mg kg, unacceptable intubating conditions are more common. Succinylcholine 1.5 mg kg does not produce more often excellent conditions compared with 1 mg kg, while 2.0 mg kg does, but the database with these regimens is weak and apnoea times remain unknown. Limited information size and strong statistical heterogeneity decrease the certainty of the evidence.
Topics: Dose-Response Relationship, Drug; Humans; Neuromuscular Depolarizing Agents; Randomized Controlled Trials as Topic; Rapid Sequence Induction and Intubation; Succinylcholine
PubMed: 32122305
DOI: 10.1186/s12871-020-00968-1 -
The Cochrane Database of Systematic... May 2017Tracheal intubation during induction of general anaesthesia is a vital procedure performed to secure a patient's airway. Several studies have identified difficult... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tracheal intubation during induction of general anaesthesia is a vital procedure performed to secure a patient's airway. Several studies have identified difficult tracheal intubation (DTI) or failed tracheal intubation as one of the major contributors to anaesthesia-related mortality and morbidity. Use of neuromuscular blocking agents (NMBA) to facilitate tracheal intubation is a widely accepted practice. However, because of adverse effects, NMBA may be undesirable. Cohort studies have indicated that avoiding NMBA is an independent risk factor for difficult and failed tracheal intubation. However, no systematic review of randomized trials has evaluated conditions for tracheal intubation, possible adverse effects, and postoperative discomfort.
OBJECTIVES
To evaluate the effects of avoiding neuromuscular blocking agents (NMBA) versus using NMBA on difficult tracheal intubation (DTI) for adults and adolescents allocated to tracheal intubation with direct laryngoscopy. To look at various outcomes, conduct subgroup and sensitivity analyses, examine the role of bias, and apply trial sequential analysis (TSA) to examine the level of available evidence for this intervention.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, LILACS, advanced Google, CINAHL, and the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and www.centerwatch.com, up to January 2017. We checked the reference lists of included trials and reviews to look for unidentified trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared the effects of avoiding versus using NMBA in participants 14 years of age or older.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data independently. We conducted random-effects and fixed-effect meta-analyses and calculated risk ratios (RRs) and their 95% confidence intervals (CIs). We used published data and data obtained by contacting trial authors. To minimize the risk of systematic error, we assessed the risk of bias of included trials. To reduce the risk of random errors caused by sparse data and repetitive updating of cumulative meta-analyses, we applied TSA.
MAIN RESULTS
We identified 34 RCTs with 3565 participants that met our inclusion criteria. All trials reported on conditions for tracheal intubation; seven trials with 846 participants described 'events of upper airway discomfort or injury', and 13 trials with 1308 participants reported on direct laryngoscopy. All trials used a parallel design. We identified 18 dose-finding studies that included more interventions or control groups or both. All trials except three included only American Society of Anesthesiologists (ASA) class I and II participants, 25 trials excluded participants with anticipated DTI, and obesity or overweight was an excluding factor in 13 studies. Eighteen trials used suxamethonium, and 18 trials used non-depolarizing NMBA.Trials with an overall low risk of bias reported significantly increased risk of DTI with no use of NMBA (random-effects model) (RR 13.27, 95% CI 8.19 to 21.49; P < 0.00001; 508 participants; four trials; number needed to treat for an additional harmful outcome (NNTH) = 1.9, I = 0%, D = 0%, GRADE = moderate). The TSA-adjusted CI for the RR was 1.85 to 95.04. Inclusion of all trials resulted in confirmation of results and of significantly increased risk of DTI when an NMBA was avoided (random-effects model) (RR 5.00, 95% CI 3.49 to 7.15; P < 0.00001; 3565 participants; 34 trials; NNTH = 6.3, I = 70%, D = 82%, GRADE = low). Again the cumulative z-curve crossed the TSA monitoring boundary, demonstrating harmful effects of avoiding NMBA on the proportion of DTI with minimal risk of random error. We categorized only one trial reporting on upper airway discomfort or injury as having overall low risk of bias. Inclusion of all trials revealed significant risk of upper airway discomfort or injury when an NMBA was avoided (random-effects model) (RR 1.37, 95% CI 1.09 to 1.74; P = 0.008; 846 participants; seven trials; NNTH = 9.1, I = 13%, GRADE = moderate). The TSA-adjusted CI for the RR was 1.00 to 1.85. None of these trials reported mortality. In terms of our secondary outcome 'difficult laryngoscopy', we categorized only one trial as having overall low risk of bias. All trials avoiding NMBA were significantly associated with difficult laryngoscopy (random-effects model) (RR 2.54, 95% CI 1.53 to 4.21; P = 0.0003; 1308 participants; 13 trials; NNTH = 25.6, I = 0%, D= 0%, GRADE = low); however, TSA showed that only 6% of the information size required to detect or reject a 20% relative risk reduction (RRR) was accrued, and the trial sequential monitoring boundary was not crossed.
AUTHORS' CONCLUSIONS
This review supports that use of an NMBA may create the best conditions for tracheal intubation and may reduce the risk of upper airway discomfort or injury following tracheal intubation. Study results were characterized by indirectness, heterogeneity, and high or uncertain risk of bias concerning our primary outcome describing difficult tracheal intubation. Therefore, we categorized the GRADE classification of quality of evidence as moderate to low. In light of defined outcomes of individual included trials, our primary outcomes may not reflect a situation that many clinicians consider to be an actual difficult tracheal intubation by which the patient's life or health may be threatened.
Topics: Adolescent; Adult; Confidence Intervals; Humans; Intubation, Intratracheal; Laryngoscopy; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Randomized Controlled Trials as Topic; Risk Factors; Sensitivity and Specificity; Succinylcholine
PubMed: 28513831
DOI: 10.1002/14651858.CD009237.pub2 -
Frontiers in Oncology 2021Paragangliomas (PGLs) are neuroendocrine neoplasms arising from chromaffin cells of sympathetic or parasympathetic paraganglia. Systemic therapies have been used only in...
BACKGROUND
Paragangliomas (PGLs) are neuroendocrine neoplasms arising from chromaffin cells of sympathetic or parasympathetic paraganglia. Systemic therapies have been used only in metastatic PGLs. Antiangiogenic agents, such as sunitinib, could be a viable therapeutic choice in the subgroup of patients with -positive PGLs. We describe the case of a man with Familial Paraganglioma Syndrome type 1 (FPGL) related to a novel mutation in gene treated with sunitinib. Furthermore, we performed a systematic review of the literature aimed to address the following question: is sunitinib treatment effective in patients with advanced/progressive/metastatic PGL?
METHODS
We performed a data search using MEDLINE, Cochrane Library, and Scopus between April 2019 and September 2020. We included studies reporting data on clinical or biological characteristics, or clinical outcomes of patients with PGLs treated with sunitinib.
RESULTS
The search leaded to the selection of 25 publications. Data from case reports and case series showed that disease control rate (DCR = stable disease + partial response + complete response) was achieved in 34.7% of cases under sunitinib treatment. In 39% of patients DCR was followed by progressive disease (PD) or tumor relapse, 26.1% patients showed PD. Data from clinical trials showed that DCR was 83%, and the median progression free survival was 13.4 months.
DISCUSSION
Data from the present literature review suggested that sunitinib could be a viable therapeutic option in advanced/progressive/metastatic inoperable PGLs. However, further trials on the efficacy of sunitinib in FPGL and sporadic PGL are needed.
PubMed: 34221997
DOI: 10.3389/fonc.2021.677983 -
Anaesthesia Jun 2017This systemic review was performed to determine whether rocuronium creates intubating conditions comparable to those of succinylcholine during rapid sequence intubation... (Comparative Study)
Comparative Study
This systemic review was performed to determine whether rocuronium creates intubating conditions comparable to those of succinylcholine during rapid sequence intubation of the trachea. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 2), MEDLINE (1966 to February Week 2 2015), and EMBASE (1988 to February 14 2015) for any randomised controlled trials or controlled clinical trials that reported intubating conditions comparing rocuronium and succinylcholine for rapid or modified rapid sequence intubation. The dose of rocuronium was at least 0.6 mg.kg and succinylcholine was at least 1 mg.kg . Sixty-six studies were identified and 50 included, representing 4151 participants. Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions (risk ratio (95%CI) 0.86 (0.81 to 0.92), n = 4151) and clinically acceptable intubation conditions (risk ratio (95%CI) 0.97 (0.95-0.99), n = 3992). A high incidence of detection bias amongst the trials coupled with significant heterogeneity means that the quality of evidence was moderate for these conclusions. Succinylcholine was more likely to produce excellent intubating conditions when using thiopental as the induction agent: risk ratio (95%CI) 0.81 (0.73-0.88), n = 2302) with or without the use of opioids (risk ratio (95%CI) 0.85 (0.78-0.93), n = 2292 or 0.85 (0.76-0.95), n = 1428).
Topics: Humans; Intubation, Intratracheal; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Randomized Controlled Trials as Topic; Rocuronium; Succinylcholine
PubMed: 28654173
DOI: 10.1111/anae.13903 -
Australian Family Physician Mar 2017Overactive bladder syndrome (OAB) is a common medical condition that causes significant distress and impact on the quality of life in women. Muscarinic receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Overactive bladder syndrome (OAB) is a common medical condition that causes significant distress and impact on the quality of life in women. Muscarinic receptor antagonists remain the mainstay of therapy, but they are limited by their efficacy and adverse effects. The objective of the article was to compare the clinical efficacy and tolerability of medications used to treat OAB in women through network meta-analysis.
METHODS
Data from eligible studies of commonly prescribed pharmacological agents in the treatment of OAB in women were entered into Net-MetaXL after a literature search using two online databases (PubMed and Cochrane). Studies between 31 July 2000 and 31 July 2015 were included in this study.
RESULTS
Five quantitative studies were eligible for analysis. The most efficacious drug to treat OAB in women appears to be solifenacin 10 mg once daily (OD), followed by oxybutynin 3 mg three times a day. However, solifenacin 10 mg OD caused more adverse effects that the other treatments.
DISCUSSION
Our results are similar to those of another systematic review. When considering efficacy, tolerability and cost, solifenacin 5 mg once daily is the drug of choice as it is more efficacious, albeit with more adverse effects, than other treatments. If solifenacin is unsuitable, oxybutynin 3 mg TDS is recommended.
Topics: Dose-Response Relationship, Drug; Female; Humans; Mandelic Acids; Randomized Controlled Trials as Topic; Solifenacin Succinate; Urinary Bladder, Overactive; Urological Agents; Women's Health
PubMed: 28260277
DOI: No ID Found -
PloS One 2020RDoC conceptualises psychopathology as neurobiologically-rooted behavioural psychological "constructs" that span dimensionally from normality to pathology, but its...
Exploring the utility of RDoC in differentiating effectiveness amongst antidepressants: A systematic review using proposed psychometrics as the unit of analysis for the Negative Valence Systems domain.
BACKGROUND
RDoC conceptualises psychopathology as neurobiologically-rooted behavioural psychological "constructs" that span dimensionally from normality to pathology, but its clinical utility remains controversial.
AIM
To explore RDoC's potential clinical utility by examining antidepressant effectiveness through Negative Valence Systems (NVS) domain constructs.
METHOD
A systematic review was conducted on Web of Science, MEDLINE, EMBASE and PsycINFO for antidepressant trials that included psychometric instruments assessed by Watson, Stanton & Clark (2017) to represent NVS constructs of Acute Threat, Potential Threat and Loss.
RESULTS
221 citations were identified; 13 were included in qualitative synthesis, none for quantitative analysis. All suffered from significant bias risks. 9 antidepressants were investigated, most within 1 construct, and most were found to be effective. Paroxetine, citalopram and fluvoxamine were found to be effective for Acute Threat, fluoxetine, desvenlafaxine and sertraline for Potential Threat, and sertraline, fluvoxamine, fluoxetine and desvenlafaxine effective for Loss. Nefazodone was found to be ineffective for acute fear.
CONCLUSION
Preliminary evidence supports RDoC NVS constructs' clinical utility in assessing antidepressant effectiveness, but lack of discriminant validity between Potential Threat and Loss supports their recombination into a single Distress construct. Finding of effectiveness within "normal" construct levels support the utility of a dimensional approach. Testable hypotheses were generated that can further test RDoC's clinical utility.
Topics: Algorithms; Antidepressive Agents; Citalopram; Clinical Trials as Topic; Depressive Disorder; Desvenlafaxine Succinate; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Psychometrics; Sertraline; Treatment Outcome
PubMed: 33326436
DOI: 10.1371/journal.pone.0243057