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Journal of Cancer 2024Immune-activating anti-CTLA4 and anti-PD1 monoclonal antibodies (alone or in combination) are being used to treat advanced melanoma patients and can lead to durable... (Review)
Review
Immune-activating anti-CTLA4 and anti-PD1 monoclonal antibodies (alone or in combination) are being used to treat advanced melanoma patients and can lead to durable remissions, and long-term overall survival may be achieved in between 50-60% of patients. Although intracranial metastases are very common in melanoma (about 50-75% of all patients with advanced disease), most of the pivotal prospective clinical trials exclude patients with intra-cranial metastases, certainly if their lesions are symptomatic and steroid-requiring and the degree of sensitivity of intra-cranial melanoma to immunotherapy remains uncertain, and requires further investigation especially in view of the demonstrable activity of RAF-MEK inhibitors in this clinical setting and the emergence of stereotactic radiotherapy. Our study aimed to evaluate the efficacy and toxicity of immunotherapy against advanced melanoma patients with brain metastases. In terms of comparative studies, only retrospective analyses could be identified. Based on 3 retrospective studies, treatment of patients with melanoma brain metastases with immunotherapeutic approaches improves overall survival substantially compared with supportive measures alone (no active anticancer treatment). The efficacy of targeted therapy appeared to be comparable to that of immune therapy in terms of overall survival, based on a small number of patients. The combination of concurrent radiation therapy to the brain and systemic immunotherapy led to improved overall survival compared to radiotherapy alone, suggesting potential synergism between the approaches, and combination treatment could be delivered safely. Our review supports the use of immunotherapeutic strategies for these patients although treatment efficacy appears to be lower for symptomatic lesions. In view of the extremely high efficacy of stereotactic radiotherapy approaches in the brain, understanding the interaction between radiotherapy and immunotherapy is vital and should be an area of active investigation.
PubMed: 38817862
DOI: 10.7150/jca.93306 -
PloS One 2024This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment. (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVES
This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment.
METHODS
A computerized search through PubMed/MEDLINE, SCOPUS, and the Cochrane Library was conducted to find relevant papers. We used the "netmeta" and "meta" packages for network meta-analysis (NMA) in RStudio 1.2.5019 (2009-2019 RStudio, Inc.) to conduct all of our statistical tests.
RESULTS
Seven articles (n = 2,006 patients) were included. The fixed-effect size showed that TC 1% bis in die (BID) showed potential effectiveness in reducing the inflammatory and non-inflammatory lesion count compared to placebo (Standardized mean difference, SMD = -0.27, 95% CI: -0.36 to -0.17) and (SMD = -0.31, 95% CI: -0.41 to -0.22), respectively. The random-effect size showed that TC 1% BID was significantly associated with a 12-week treatment success compared to placebo (Odds ratio, OR = 2.44, 95% CI: 1.12 to 5.30). Spironolactone 200 mg was associated with a significant reduction in total lesion count (SMD = -4.46, 95% CI: -5.60 to -3.32).
CONCLUSION
TC appears to reduce both inflammatory and non-inflammatory lesion count and may lead to treatment success. Spironolactone at 200 mg showed potential effectiveness in terms of total lesion count reduction. These results suggest that both TC and Spironolactone could be beneficial in treating patients with acne vulgaris.
Topics: Acne Vulgaris; Humans; Spironolactone; Network Meta-Analysis; Treatment Outcome; Administration, Topical; Cortodoxone; Propionates
PubMed: 38814916
DOI: 10.1371/journal.pone.0298155 -
Annals of Medicine Dec 2024Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults.
METHODS
We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554.
RESULTS
We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity between the studies was low.
CONCLUSIONS
Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).
Topics: Humans; Tension-Type Headache; Analgesics; Adult; Network Meta-Analysis; Ibuprofen; Acetaminophen; Bayes Theorem; Treatment Outcome; Diclofenac; Randomized Controlled Trials as Topic; Naproxen; Ketoprofen; Anti-Inflammatory Agents, Non-Steroidal; Female; Male
PubMed: 38813682
DOI: 10.1080/07853890.2024.2357235 -
Indian Journal of Orthopaedics Jun 2024The most effective injective treatment approach for sacroiliac joint (SIJ) pain remains unclear. Aim of this study was to quantify the safety and effectiveness of the... (Review)
Review
BACKGROUND
The most effective injective treatment approach for sacroiliac joint (SIJ) pain remains unclear. Aim of this study was to quantify the safety and effectiveness of the available injective strategies to address SIJ pain.
METHODS
A systematic review and meta-analysis of the literature was conducted on PubMed, Scopus, and Embase databases from inception until January 2023. Inclusion criteria were studies written in English, comparative and non-comparative studies regardless of the minimum follow-up, and case series on SIJ injections. Safety and efficacy of the different injection therapies for the SIJ were quantified. A meta-analysis was conducted on the available data of the documented injective therapies. The "Checklist for Measuring Quality" by Downs and Black was used to assess the risk of bias and the quality of papers.
RESULTS
The literature search retrieved 43 papers (2431 patients): 16 retrospective case series, 2 retrospective comparative studies, 17 prospective case series, 3 prospective comparative studies, and 5 randomized controlled trials. Of the selected studies, 63% examined the effect of steroid injections, 16% of PRP injections, while 21% reported other heterogeneous treatments. The failure rate was 26% in steroid injections and 14% in PRP injections. The meta-analysis showed a statistically significant reduction in pain with the VAS score for both steroids and PRP: steroids improvement at mid-term 3.4 points ( < 0.05), at long-term 3.0 ( < 0.05), PRP improvement at mid-term 2.2 ( = 0.007), at long-term 2.3 points of the VAS pain scale ( = 0.02).
CONCLUSIONS
Steroids are the most documented injective approach, with studies showing an overall safety and effectiveness. Still, the high number of failures underlined by some studies suggest the need for alternative procedures. Early PRP data showed promise, but the limitations of the current literature do not allow to clearly define the most suitable injective approach, and further studies are needed to identify the best injective treatment for SIJ patients.
PubMed: 38812868
DOI: 10.1007/s43465-024-01164-w -
Plastic and Reconstructive Surgery Jun 2024
Meta-Analysis Comparative Study
Discussion: Comparing Combination Triamcinolone Acetonide and 5-Fluorouracil with Monotherapy Triamcinolone Acetonide or 5-Fluorouracil in the Treatment of Hypertrophic Scars: A Systematic Review and Meta-Analysis.
Topics: Humans; Cicatrix, Hypertrophic; Triamcinolone Acetonide; Fluorouracil; Drug Therapy, Combination; Glucocorticoids; Treatment Outcome; Meta-Analysis as Topic
PubMed: 38810159
DOI: 10.1097/PRS.0000000000011351 -
Frontiers in Endocrinology 2024This systematic review and meta-analysis was conducted to compare the benefits of adrenalectomy and conservative treatment for comorbidities associated with mild... (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVE
This systematic review and meta-analysis was conducted to compare the benefits of adrenalectomy and conservative treatment for comorbidities associated with mild autonomous cortisol secretion (MACS) in patients diagnosed with MACS.
BACKGROUND
MACS is the most common benign hormone-secreting functional adrenal incidentaloma. Overproduction of cortisol is observed in MACS patients, resulting in a variety of long-term health issues, including arterial hypertension (HTN), diabetes mellitus (DM), dyslipidemia, obesity, and osteoporosis; however, the classic clinical manifestations of Cushing's syndrome (CS) are not present.
METHODS
A systematic search was conducted using MEDLINE, Embase, Web of Sciences, and Scopus databases on December, 2023. Two reviewers independently extracted data and assessed the quality of the included articles. A meta-analysis was performed to compare the beneficial effects of adrenalectomy versus conservative management for MACS-related comorbidities.
RESULTS
Fifteen articles were included in this study, which evaluated 933 MACS patients (384 Adrenalectomy and 501 Conservative treatment, and 48 excluded due to incomplete follow-up duration). MACS diagnosis criteria were different among the included articles. All studies, however, stated that there must be no overt CS symptoms. Meta-analysis demonstrates the overall advantage of adrenalectomy over conservative treatment for MACS-related comorbidities (Cohen's d = -0.49, 95% CI [-0.64, -0.34], p = 0.00). Subgroup analysis indicated that the systolic blood pressure (pooled effect size = -0.81, 95% CI [-1.19, -0.42], p = 0.03), diastolic blood pressure (pooled effect size = -0.63, 95% CI [-1.05, -0.21], p = 0.01), and BMD (pooled effect size = -0.40, 95% CI [-0.73, -0.07], p = 0.02) were significantly in favor of adrenalectomy group rather than conservative treatment but no significant differences between the two treatment groups in other MACS-related comorbidities were reported.
CONCLUSION
Despite the limited and diverse data, this study demonstrates the advantage of adrenalectomy over conservative treatment for MACS-related comorbidities.
Topics: Humans; Adrenalectomy; Hydrocortisone; Adrenal Gland Neoplasms; Conservative Treatment; Cushing Syndrome; Hypertension
PubMed: 38808111
DOI: 10.3389/fendo.2024.1374711 -
Psychopharmacology Jul 2024Zuranolone, a newly FDA-approved synthetic neurosteroid, shows promise in treating depression. (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Zuranolone, a newly FDA-approved synthetic neurosteroid, shows promise in treating depression.
OBJECTIVES
Our aim is to evaluate Zuranolone's efficacy and safety in treating depression.
METHODS
Five databases were searched until September 2023 for relevant randomized clinical trials evaluating the efficacy and safety of zuranolone. The potential risk of bias in the included trials was evaluated by the Cochrane Risk of Bias II guideline Data were extracted and pooled using Review Manager Software (RevMan 5.3).
RESULTS
An analysis of eight studies highlights Zuranolone's efficacy in treating depression compared to placebo across most of the outcomes. Notably, the 30mg and 50mg doses demonstrated significant improvements in reducing HAM-D scores by over 50% within a 15-day follow-up (RR) of 1.46 (95% CI [1.27, 1.68], p < 0.0001) and 1.14 (95% CI [1.01, 1.3], p = 0.04). Additionally, the HAM-D ≤ 7% score analysis revealed significant enhancements with the 30mg dose over both 15-day (RR = 1.82, 95% CI [1.44, 2.31], p < 0.0001) and 45-day (RR = 1.43, 95% CI [1.16, 1.77], p = 0.0008) durations. Adverse Events Drug Discontinuation demonstrated no overall significant difference (OR = 1.33, 95% CI: [0.79, 2.23], p = 0.282). Further, specific adverse events, such as headache, showed no significant overall difference between Zuranolone and placebo (OR = 1.11, 95% CI: [0.84, 1.47], p = 0.47), with dose-dependent analysis revealing less headache in the 30 mg group.
CONCLUSION
Zuranolone demonstrates favorable tolerability and safety, particularly at 30mg and 50mg doses after 15 days, suggesting its potential and effective treatment for depression.
Topics: Humans; Randomized Controlled Trials as Topic; Antidepressive Agents; Depression; Dose-Response Relationship, Drug; Treatment Outcome; Pregnanolone; Pyrazoles
PubMed: 38802705
DOI: 10.1007/s00213-024-06611-y -
CJEM May 2024Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of...
OBJECTIVES
Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of evidence. The objective was to determine if anti-inflammatory medication (non-steroidal anti-inflammatory drugs [NSAIDs], corticosteroids) as adjunct cellulitis treatment improves clinical response and cure.
METHODS
Systematic review and meta-analysis including randomized controlled trials of patients with cellulitis treated with antibiotics irrespective of age, gender, severity and setting, and an intervention of anti-inflammatories (NSAIDs or corticosteroids) vs. placebo or no intervention. Medline (PubMed), Embase (via Elsevier), and Cochrane CENTRAL were searched from inception to August 1, 2023. Data extraction was conducted independently in pairs. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Data were pooled using a random effects model. Primary outcomes are time to clinical response and cure.
RESULTS
Five studies (n = 331) were included, all were adults. Three trials reported time to clinical response. There was a benefit with use of an oral NSAID as adjunct therapy at day 3 (risk ratio 1.81, 95%CI 1.42-2.31, I = 0%). There was no difference between groups at day 5 (risk ratio 1.19, 95%CI 0.62-2.26), although heterogeneity was high (I = 96%). Clinical cure was reported by three trials, and there was no difference between groups at all timepoints up to 22 days. Statistical heterogeneity was moderate to low. Adverse events (N = 3 trials) were infrequent.
CONCLUSIONS
For patients with cellulitis, the best available data suggest that oral nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunct therapy to antibiotics may lead to improved early clinical response, although this is not sustained beyond 4 days. There is insufficient data to comment on the role of corticosteroids for clinical response. These results must be interpreted with caution due to the small number of included studies.
REGISTRATION
Open Science Framework: https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .
PubMed: 38796807
DOI: 10.1007/s43678-024-00718-z -
Nutrients May 2024Previous studies have shown encouraging results regarding the efficacy and safety of nutraceuticals, such as "red yeast rice (RYR) extract", on reducing... (Meta-Analysis)
Meta-Analysis Review
Safety and Efficacy of the Consumption of the Nutraceutical "Red Yeast Rice Extract" for the Reduction of Hypercholesterolemia in Humans: A Systematic Review and Meta-Analysis.
Previous studies have shown encouraging results regarding the efficacy and safety of nutraceuticals, such as "red yeast rice (RYR) extract", on reducing hypercholesterolemia in humans. A systematic review and meta-analysis was conducted from January 2012 to May 2022. The search was strictly focused on clinical trials that examined the association between RYR extract consumption and parameters of the lipid profile in humans. Fourteen double-blinded clinical trials were identified. The interventions lasted 4-24 weeks. In most studies, there was one intervention group and one control group. RYR extract consumption statistically significantly reduced total cholesterol (mean absolute reduction: 37.43 mg/dL; 95% confidence interval [CI]: -47.08, -27.79) and low-density lipoprotein cholesterol (LDL-C; mean absolute reduction: 35.82 mg/dL; 95% CI: -43.36, -28.29), but not high-density lipoprotein cholesterol, triglycerides and apolipoproteins A-I and B. As regards the safety, RYR extract was considered a safe choice with neither threatening nor frequent side effects. The consumption of RYR extract by people with hypercholesterolemia was associated with statistically significant reduction in total cholesterol and LDL-C, whereas it was not associated with an increase in life-threatening side effects. Further research on specific subpopulations and outcomes could establish a consensus on determining the clinical benefits and potential risks, if any, of this nutraceutical.
Topics: Adult; Humans; Middle Aged; Anticholesteremic Agents; Biological Products; Cholesterol; Cholesterol, LDL; Dietary Supplements; Hypercholesterolemia; Treatment Outcome; Young Adult; Aged; Aged, 80 and over
PubMed: 38794691
DOI: 10.3390/nu16101453 -
International Journal of Molecular... May 2024The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated... (Review)
Review
The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.
Topics: Humans; Epilepsy; Nuclear Receptor Subfamily 4, Group A, Member 2; Developmental Disabilities; Intellectual Disability
PubMed: 38791237
DOI: 10.3390/ijms25105198