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BMJ Mental Health Oct 2023This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
QUESTION
This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
STUDY SELECTION AND ANALYSIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed.
FINDINGS
Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio.
CONCLUSIONS
The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.
Topics: Humans; Acetylcysteine; Amino Acids; Anti-Inflammatory Agents; Antipsychotic Agents; Schizophrenia; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37852631
DOI: 10.1136/bmjment-2023-300771 -
The Indian Journal of Radiology &... Oct 2023High-grade gliomas (HGGs) are the most prevalent primary malignancy of the central nervous system. The tumor results in vasogenic and infiltrative edema . Exact... (Review)
Review
High-grade gliomas (HGGs) are the most prevalent primary malignancy of the central nervous system. The tumor results in vasogenic and infiltrative edema . Exact anatomical differentiation of these edemas is so important for surgical planning. Multimodal imaging could be used to differentiate the edema type. The aim of this study was to investigate the role of multimodal imaging in the differentiation of vasogenic edema from infiltrative edema in patients with HGG (grade III and grade IV). A search on PubMed, EMBASE, Scopus, and ISI Web of Science Core Collection up to June 2022 using terms related to (a) multimodal imaging AND (b) HGG AND (c) edema. (PROSPERO registration number: CRD42022336131) Two reviewers screened the articles and independently extracted the data. We included original articles assessing the role of multimodal imaging in differentiating vasogenic from infiltrative edema in patients with HGG. Six high-quality articles remained for the narrative synthesis. Dynamic susceptibility contrast imaging showed that relative cerebral blood volume and relative cerebral blood flow were higher in the infiltrative edema component than in the vasogenic edema component. Diffusion tensor imaging revealed a dispute on fractional anisotropy. The apparent diffusion coefficient was comparable between the two edematous components. Magnetic resonance spectroscopy exhibited an increment in choline/creatinine ratio and choline/N-acetyl aspartate ratio in the infiltrative edema component. Strict study selection, low sample size of relevant published studies, and heterogeneity in endpoint variables were the major drawbacks. Multimodal imaging, including dynamic susceptibility contrast and magnetic resonance spectroscopy, might help differentiate between vasogenic and infiltrative edema.
PubMed: 37811185
DOI: 10.1055/s-0043-1772466 -
Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
Journal of Genetics and Genomics = Yi... Mar 2024Protein post-translational modifications (PTMs), such as ubiquitination, phosphorylation, and small ubiquitin-like modifier (SUMO)ylation, are crucial for regulating...
Protein post-translational modifications (PTMs), such as ubiquitination, phosphorylation, and small ubiquitin-like modifier (SUMO)ylation, are crucial for regulating protein stability, activity, subcellular localization, and binding with cofactors. Such modifications remarkably increase the variety and complexity of proteomes, which are essential for regulating numerous cellular and physiological processes. The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development. Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations. Thus, a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes. This review discusses the progress of protein ubiquitination, phosphorylation, histone acetylation and methylation, SUMOylation, and S-nitrosylation in the regulation of auxin signaling.
Topics: Indoleacetic Acids; Protein Processing, Post-Translational; Signal Transduction; Sumoylation; Ubiquitination
PubMed: 37451336
DOI: 10.1016/j.jgg.2023.07.002 -
Diabetology International Jul 2023Cardiovascular autonomic neuropathy (CAN) is a debilitating complication of diabetes mellitus. To date, there is no systematic review on all the available drug... (Review)
Review
BACKGROUND
Cardiovascular autonomic neuropathy (CAN) is a debilitating complication of diabetes mellitus. To date, there is no systematic review on all the available drug treatments for CAN in diabetic patients, except for one review focusing on aldose reductase inhibitors.
OBJECTIVE
To evaluate available drug treatment options for CAN in diabetic patients.
METHODS
A systematic review was conducted with a search of CENTRAL, Embase, PubMed and Scopus from database inception till 14th May 2022. Randomised controlled trials (RCTs) of diabetic patients with CAN that investigated the effect of treatment on blood pressure, heart rate variability, heart rate or QT interval were included.
RESULTS
Thirteen RCTs with a total of 724 diabetic patients with CAN were selected. There was a significant improvement in the autonomic indices of diabetic patients with CAN given angiotensin-converting enzyme inhibitor (ACEI) for 24 weeks (<0.05) to two years (<0.001), angiotensin-receptor blocker (ARB) for one year (<0.05), single dose of beta blocker (BB) (<0.05), omega-3 polyunsaturated fatty acids (PUFAs) for three months (<0.05), alpha-lipoic acid (ALA) for four months ( < 0.05) to six months (=0.048), vitamin B12 in combination with ALA, acetyl L‑carnitine (ALC), superoxide dismutase (SOD) for one year (=0.001) and near significant improvement in the autonomic indices of diabetic patients with CAN given vitamin E for four months ( = 0.05) compared to the control group. However, there was no significant improvement in the autonomic indices of patients given vitamin B12 monotherapy ( ≥ 0.05).
CONCLUSION
ACEI, ARB, BB, ALA, omega-3 PUFAs, vitamin E, vitamin B12 in combination with ALA, ALC and SOD could be effective treatment options for CAN, while vitamin B12 monotherapy might be unlikely to be recommended for the treatment of CAN due to its lack of efficacy.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s13340-023-00629-x.
PubMed: 37397902
DOI: 10.1007/s13340-023-00629-x -
The Cochrane Database of Systematic... Jun 2023Advanced chronic liver disease is characterised by a long compensated phase followed by a rapidly progressive 'decompensated' phase, which is marked by the development... (Review)
Review
Granulocyte colony-stimulating factor with or without stem or progenitor cell or growth factors infusion for people with compensated or decompensated advanced chronic liver disease.
BACKGROUND
Advanced chronic liver disease is characterised by a long compensated phase followed by a rapidly progressive 'decompensated' phase, which is marked by the development of complications of portal hypertension and liver dysfunction. Advanced chronic liver disease is considered responsible for more than one million deaths annually worldwide. No treatment is available to specifically target fibrosis and cirrhosis; liver transplantation remains the only curative option. Researchers are investigating strategies to restore liver functionality to avoid or slow progression towards end-stage liver disease. Cytokine mobilisation of stem cells from the bone marrow to the liver could improve liver function. Granulocyte colony-stimulating factor (G-CSF) is a 175-amino-acid protein currently available for mobilisation of haematopoietic stem cells from the bone marrow. Multiple courses of G-CSF, with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, might be associated with accelerated hepatic regeneration, improved liver function, and survival.
OBJECTIVES
To evaluate the benefits and harms of G-CSF with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, compared with no intervention or placebo in people with compensated or decompensated advanced chronic liver disease.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two trial registers (October 2022) together with reference-checking and web-searching to identify additional studies. We applied no restrictions on language and document type.
SELECTION CRITERIA
We only included randomised clinical trials comparing G-CSF, independent of the schedule of administration, as a single treatment or combined with stem or progenitor cell infusion, or with other medical co-interventions, with no intervention or placebo, in adults with chronic compensated or decompensated advanced chronic liver disease or acute-on-chronic liver failure. We included trials irrespective of publication type, publication status, outcomes reported, or language.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane procedures. All-cause mortality, serious adverse events, and health-related quality of life were our primary outcomes, and liver disease-related morbidity, non-serious adverse events, and no improvement of liver function scores were our secondary outcomes. We undertook meta-analyses, based on intention-to-treat, and presented results using risk ratios (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI) and I statistic values as a marker of heterogeneity. We assessed all outcomes at maximum follow-up. We determined the certainty of evidence using GRADE, evaluated the risk of small-study effects in regression analyses, and conducted subgroup and sensitivity analyses.
MAIN RESULTS
We included 20 trials (1419 participants; sample size ranged from 28 to 259), which lasted between 11 and 57 months. Nineteen trials included only participants with decompensated cirrhosis; in one trial, 30% had compensated cirrhosis. The included trials were conducted in Asia (15), Europe (four), and the USA (one). Not all trials provided data for our outcomes. All trials reported data allowing intention-to-treat analyses. The experimental intervention consisted of G-CSF alone or G-CSF plus any of the following: growth hormone, erythropoietin, N-acetyl cysteine, infusion of CD133-positive haemopoietic stem cells, or infusion of autologous bone marrow mononuclear cells. The control group consisted of no intervention in 15 trials and placebo (normal saline) in five trials. Standard medical therapy (antivirals, alcohol abstinence, nutrition, diuretics, β-blockers, selective intestinal decontamination, pentoxifylline, prednisolone, and other supportive measures depending on the clinical status and requirement) was administered equally to the trial groups. Very low-certainty evidence suggested a decrease in mortality with G-CSF, administered alone or in combination with any of the above, versus placebo (RR 0.53, 95% CI 0.38 to 0.72; I = 75%; 1419 participants; 20 trials). Very low-certainty evidence suggested no difference in serious adverse events (G-CSF alone or in combination versus placebo: RR 1.03, 95% CI 0.66 to 1.61; I = 66%; 315 participants; three trials). Eight trials, with 518 participants, reported no serious adverse events. Two trials, with 165 participants, used two components of the quality of life score for assessment, with ranges from 0 to 100, where higher scores indicate better quality of life, with a mean increase from baseline of the physical component summary of 20.7 (95% CI 17.4 to 24.0; very low-certainty evidence) and a mean increase from baseline of the mental component summary of 27.8 (95% CI 12.3 to 43.3; very low-certainty evidence). G-CSF, alone or in combination, suggested a beneficial effect on the proportion of participants who developed one or more liver disease-related complications (RR 0.40, 95% CI 0.17 to 0.92; I = 62%; 195 participants; four trials; very low-certainty evidence). When we analysed the occurrences of single complications, there was no suggestion of a difference between G-CSF, alone or in combination, versus control, in participants in need of liver transplantation (RR 0.85, 95% CI 0.39 to 1.85; 692 participants; five trials), in the development of hepatorenal syndrome (RR 0.65, 95% CI 0.33 to 1.30; 520 participants; six trials), in the occurrence of variceal bleeding (RR 0.68, 95% CI 0.37 to 1.23; 614 participants; eight trials), and in the development of encephalopathy (RR 0.56, 95% CI 0.31 to 1.01; 605 participants; seven trials) (very low-certainty evidence). The same comparison suggested that G-CSF reduces the development of infections (including sepsis) (RR 0.50, 95% CI 0.29 to 0.84; 583 participants; eight trials) and does not improve liver function scores (RR 0.67, 95% CI 0.53 to 0.86; 319 participants; two trials) (very low-certainty evidence).
AUTHORS' CONCLUSIONS
G-CSF, alone or in combination, seems to decrease mortality in people with decompensated advanced chronic liver disease of whatever aetiology and with or without acute-on-chronic liver failure, but the certainty of evidence is very low because of high risk of bias, inconsistency, and imprecision. The results of trials conducted in Asia and Europe were discrepant; this could not be explained by differences in participant selection, intervention, and outcome measurement. Data on serious adverse events and health-related quality of life were few and inconsistently reported. The evidence is also very uncertain regarding the occurrence of one or more liver disease-related complications. We lack high-quality, global randomised clinical trials assessing the effect of G-CSF on clinically relevant outcomes.
Topics: Adult; Humans; Esophageal and Gastric Varices; Quality of Life; Acute-On-Chronic Liver Failure; Gastrointestinal Hemorrhage; Liver Cirrhosis; Stem Cells; Granulocyte Colony-Stimulating Factor; Intercellular Signaling Peptides and Proteins; Erythropoietin; Growth Hormone
PubMed: 37278488
DOI: 10.1002/14651858.CD013532.pub2 -
Antioxidants (Basel, Switzerland) Mar 2023Our aim was to review the current literature regarding the effect of antioxidant supplementation (AS) on male fertility parameters, as AS is commonly used to treat male... (Review)
Review
UNLABELLED
Our aim was to review the current literature regarding the effect of antioxidant supplementation (AS) on male fertility parameters, as AS is commonly used to treat male infertility due to the availability and affordability of antioxidants in many parts of the world.
MATERIALS AND METHODS
PubMed, Medline, and Cochrane electronic bibliographies were searched using the modified Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate studies on the benefit of antioxidant therapy on infertile men. Results were analyzed regarding the following aspects: (a) ingredient and dose; (b) potential mechanism of action and rationale for use; and (c) effect on various reported outcomes.
RESULTS
Thus, 29 studies found a substantial positive effect of AS on outcomes of assisted reproductive therapy (ART), WHO semen parameters, and live-birth rate. Carnitines, Vitamin E and C, N-acetyl cysteine, coenzyme Q10, selenium, zinc, folic acid, and lycopene were beneficial ingredients. Nevertheless, some studies did not show a substantial change in one or more factors.
CONCLUSION
AS seems to have a positive effect on male fertility. Environmental factors may play an increasing role in fertility. Further studies are needed to determine the optimal AS combination and the influence of environmental factors.
PubMed: 37107211
DOI: 10.3390/antiox12040836 -
PloS One 2023Arylamine N-acetyltransferase 2 has been related to drug side effects and cancer susceptibility; its protein structure and acetylation capacity results from the...
Arylamine N-acetyltransferase 2 has been related to drug side effects and cancer susceptibility; its protein structure and acetylation capacity results from the polymorphism's arrays on the NAT2 gene. Absorption, distribution, metabolism, and excretion, cornerstones of the pharmacological effects, have shown diversity patterns across populations, ethnic groups, and even interethnic variation. Although the 1000 Genomes Project database has portrayed the global diversity of the NAT2 polymorphisms, several populations and ethnicities remain underrepresented, limiting the comprehensive picture of its variation. The NAT2 clinical entails require a detailed landscape of its striking diversity. This systematic review spans the genetic and acetylation patterns from 164 articles from October 1992 to October 2020. Descriptive studies and controls from observational studies expanded the NAT2 diversity landscape. Our study included 243 different populations and 101 ethnic minorities, and, for the first time, we presented the global patterns in the Middle Eastern populations. Europeans, including its derived populations, and East Asians have been the most studied genetic backgrounds. Contrary to the popular perception, Africans, Latinos and Native Americans have been significantly represented in recent years. NAT2*4, *5B, and *6A were the most frequent haplotypes globally. Nonetheless, the distribution of *5B and *7B were less and more frequent in Asians, respectively. Regarding the acetylator status, East Asians and Native Americans harboured the highest frequencies of the fast phenotype, followed by South Europeans. Central Asia, the Middle East, and West European populations were the major carriers of the slow acetylator status. The detailed panorama presented herein, expands the knowledge about the diversity patterns to genetic and acetylation levels. These data could help clarify the controversial findings between acetylator states and the susceptibility to diseases and reinforce the utility of NAT2 in precision medicine.
Topics: Arylamine N-Acetyltransferase; Acetylation; Polymorphism, Genetic; Haplotypes; Phenotype; Genotype
PubMed: 37023111
DOI: 10.1371/journal.pone.0283726 -
The role of chidamide in the treatment of B-cell non-Hodgkin lymphoma: An updated systematic review.Biomolecules & Biomedicine Sep 2023B-cell non-Hodgkin lymphoma (B-NHL) is a lymphoid malignancy derived from B-cells that remains difficult to treat. Moreover, relapses and refractory cases are common.... (Review)
Review
B-cell non-Hodgkin lymphoma (B-NHL) is a lymphoid malignancy derived from B-cells that remains difficult to treat. Moreover, relapses and refractory cases are common. Abnormalities in epigenetic mechanisms, such as imbalanced histone acetylation affecting certain genes, contribute to relapses and refractory cases. Chidamide (tucidinostat) is a novel histone deacetylase inhibitor that can reverse this epigenetic imbalance and has been approved for the treatment of T-cell malignancies. However, the use of chidamide for B-NHL remains limited, and the lack of relevant literature exacerbates this limitation. We conducted this review to summarize the anticancer activity of chidamide against B-NHL and its clinical applications to overcome drug resistance. This systematic review was conducted according to the PRISMA 2020 guidelines, using some keyword combinations from MEDLINE and EBSCO. The inclusion and exclusion criteria were also defined. Of the 131 records retrieved from databases, 16 were included in the review. Nine articles revealed that chidamide limited tumor progression by modifying the tumor microenvironment, stopping the cell cycle, inducing apoptosis and autophagy, and enhancing complement-dependent and antibody-dependent cell-mediated cytotoxicities.According to seven other studies, administering chidamide in combination with another existing therapeutic regimen may benefit not only patients with relapsed/refractory B-NHL, but also those with newly diagnosed B-NHL. Chidamide plays many important roles in limiting B-NHL progression through epigenetic modifications. Thus, combining chidamide with other anticancer drugs may be more beneficial for patients with newly diagnosed and relapsed/refractory B-NHL.
Topics: Humans; Neoplasm Recurrence, Local; Lymphoma, B-Cell; Antineoplastic Agents; Aminopyridines; Tumor Microenvironment
PubMed: 37004241
DOI: 10.17305/bb.2023.8791 -
Research in Pharmaceutical Sciences Apr 2023Peripheral neuropathy is one of the most prevalent and undesirable side effects of taxane-containing chemotherapy regimens. This study aimed to investigate the effect of... (Review)
Review
BACKGROUND AND PURPOSE
Peripheral neuropathy is one of the most prevalent and undesirable side effects of taxane-containing chemotherapy regimens. This study aimed to investigate the effect of acetyl-L-carnitine (ALC) on the prevention of taxane-induced neuropathy (TIN).
EXPERIMENTAL APPROACH
MEDLINE, PubMed, Cochrane Library, Embase, Web of Science, and Google scholar were systemically applied as electronic databases from 2010 to 2019. The current systematic review was carried out based on the main considerations of PRISMA preferential reporting items for systematic review and meta-analyses. Since there was no significant discrepancy, the random-effect model was used for 12-24 weeks' analysis (I = 0%, = 0.999).
FINDINGS/RESULTS
Twelve related titles and abstracts were found during the search, 6 of them were excluded in the first phase. In the second phase, the full text of the remaining 6 articles was comprehensively evaluated and 3 papers were rejected. Finally, 3 articles complied with the inclusion criteria and pooled analyses. The meta-analysis showed a risk ratio of 0.796 (95% CI between 0.486 and 1.303), so, the effects model was used for 12-24 weeks' analysis (I = 0%, = 0.999) since no significant discrepancies were observed. There was no evidence of ALC's positive effect on the prevention of TIN during 12 weeks, and it was revealed that ALC significantly increased TIN in 24 weeks.
CONCLUSION AND IMPLICATIONS
According to our findings, the hypothesis that ALC had a positive effect on preventing TIN in 12 weeks has not been proved; however, ALC led to an increase in the TIN in 24 weeks.
PubMed: 36873277
DOI: 10.4103/1735-5362.367791