How safe and effective is irradiating radiation-induced meningiomas? Single-center experience in primary and salvage Gamma-Knife Radiosurgery, systematic review, and metanalysis of current evidence on the topic.

This is a single-center experience and metanalysis of the safety and efficacy measures of Gamma-knife stereotactic radiosurgery (SRS-GK) for radiation-induced meningiomas (RIMs). This study comprised a single-center analysis of SRS-GK for RIMs at IRCCS San Raffaele Hospital, Milan, Italy, and a systematic literature review and meta-analysis to address the actuarial local control (LC), distant control (DC), progression-free survival (PFS), and toxicity. The original series comprised 13 patients harboring 30 RIMs. Partial response was observed in 26 %, stability in 52 %, and progression in 22 %. The 5-year LC and DC rates were 71 % and 67 %. One patient developed radionecrosis, and an additional 2 presented edema. Metanalysis comprised 4 papers and data from the original series, comprising 146 patients and 308 RIMs. The 5-year LC was 84 %, the DC 67 %, and radionecrosis in 1.4 %. SRS-GK has an efficacy profile falling between that observed for radiologically suspected sporadic meningiomas and confirmed higher-grade lesions.

Cats and dogs as hosts of Blastocystis - What is the evidence?

Blastocystis is one of the most common intestinal parasites observed in human and non-human hosts. Recent meta-analyses have indicated a potential role for pets such as dogs and cats as reservoir hosts of Blastocystis, but the data underpinning this hypothesis are of mixed quality. Reviewing data for 45,894 samples tested for Blastocystis by DNA-based methods and 11,908 subtype observations, a model was developed for calculating indices that could be used for evaluating individual species as natural hosts of Blastocystis, based on weighted products of positivity rates and subtype distributions. Data from cats and dogs were analysed, using other well-sampled hosts (pig, cattle, sheep, goat, and human) as references. Data from cats and dogs meeting the inclusion criteria were entered into the model. The overall positivity rates for pigs, cattle, sheep, goats, humans, dogs, and cats were 40 %, 40 %, 35 %, 28 %, 25 %, 6 %, and 5 %, respectively, with statistically significant lower positivity rates in cats and dogs (p < 0.0001). Indices indicating Blastocystis specificity to host ranged between 0.16 (humans) and 0.49 (cattle) for the reference hosts, whereas indices for cats and dogs were only 0.01 and 0.02, respectively. Finally, indices for ST specificity to host were higher for reference hosts (range, 0.66-0.93) than for cats (0.62) and dogs (0.56). Taken together, the analyses indicate that cats and dogs are not natural or reservoir hosts of Blastocystis and that the sporadic subtype pattern observed in these hosts might indicate exposure to Blastocystis through contaminated water/feed, including Blastocystis colonizing prey animals.

Total abdominal colectomy versus diverting loop ileostomy with colonic lavage for fulminant clostridium difficile colitis: an updated systematic review and meta-analysis of outcomes.

PURPOSE: Diverting Loop Ileostomy (DLI) with intraoperative colonic lavage has emerged as a potential alternative to Total Abdominal Colectomy (TAC) for treating Fulminant Clostridium Difficile Colitis (FCDC). This study aims to provide an updated review comparing DLI with TAC in managing FCDC. METHODS: A systematic literature search was conducted using PubMed, Scopus, and Embase to identify retrospective and prospective studies comparing DLI with TAC for fulminant CDC treatment. A meta-analysis was performed to evaluate postoperative mortality rates and complications using R Studio version 4.4.1, calculating odds ratios (ORs) with 95% confidence intervals via the Mantel-Haenszel method. Heterogeneity was assessed using the Cochrane Q test and I2 statistics. RESULTS: Our search yielded 228 relevant citations, of which 7 studies with a total of 7,048 patients were included. Of these, 1,728 underwent DLI. The mean age was 63.33 years in the DLI group and 65.74 years in the TAC group. Compared to TAC, DLI had significantly lower postoperative mortality (OR 0.75; 95% CI 0.62-0.90; P = 0.002; I2 = 34%). Trial sequential analysis for postoperative mortality rates showed the benefit of DLI with a sufficiently powered sample. The DLI group also had a significantly higher rate of ostomy reversal (OR 5.68; 95% CI 2.35-13.72; P < 0.001; I2 = 36%). Postoperative complications, such as thromboembolic events, surgical site infections, urinary tract infections, renal failure, and pneumonia, were not significantly different. CONCLUSION: DLI shows a lower postoperative mortality rate and higher ostomy reversal rate than TAC, suggesting it as a potential organ-preserving, minimally invasive alternative. Further high-quality studies and trials are needed to confirm these findings.

Aberrant HIF1- α and SIX-1 Expression is Associated with Poor Prognosis in Acute Myeloid Leukemia Patients with Isocitrate Dehydrogenase 1 Mutations.

BACKGROUND: IDH1 mutations are common in many cancers, however, their role in promoting the Warburg effect remains elusive. This study elucidates the putative involvement of mutant-IDH1 in regulating hypoxia-inducible factor (HIF1-α) and Sine-Oculis Homeobox-1 (SIX-1) expression. METHODOLOGY: Genetic screening was performed using the ARMS-PCR in acute myeloid leukemia (AML), brain, and breast cancer (BC) cohorts, while transcript expression was determined using qPCR. Further, a meta-analysis of risk factors associated with the R132 mutation was performed. RESULTS: Approximately 32% of AML and ∼60% of glioma cases were mutants, while no mutation was found in the BC cohort. 'AA' and TT' were associated with higher disease risk (OR = 12.18 & 4.68) in AML and had significantly upregulated IDH1 expression. Moreover, downregulated HIF1-α and upregulated SIX-1 expression was also observed in these patients, suggesting that mutant-IDH1 may alter glucose metabolism. Perturbed IDH1 and HIF-α levels exhibited poor prognosis in univariate and multivariate analysis, while age and gender were found to be contributory factors as well. Based on the ROC model, these had a good potential to be used as prognostic markers. A significant variation in frequencies of R132 mutations in AML among different populations was observed. Cytogenesis (R2 = 12.2%), NMP1 mutation status (R2 = 18.5%), and ethnic contributions (R2 = 73.21%) were critical moderators underlying these mutations. Women had a higher risk of R132 mutation (HR = 1.3, P < 0.04). The pooled prevalence was calculated to be 0.29 (95% CI 0.26-0.33, P < 0.01), indicating that IDH1 mutations are a significant prognostic factor in AML. CONCLUSION: IDH1 and HIF1-α profiles are linked to poor survival and prognosis, while high SIX-1 expression in IDH1 mutants suggests a role in leukemic transformation and therapy response in AML.

IDH1 mutations are common in many types of cancer, but scientists have not fully understood how they contribute to the Warburg effect - a process that alters glucose metabolism in cells. In this study, we evaluate the association between mutant-IDH1 and HIF1 as well as SIX-1 gene expression. We analyzed genetic data from patients with brain cancer, breast cancer, and acute myeloid leukemia (AML), and found that roughly 32% of AML cases and 60% of glioma cases had IDH1 mutations, while no mutations were found in breast cancer. Patients with mutant genotypes had a higher risk of disease and showed upregulated IDH1 expression. They also had downregulated HIF1 and upregulated SIX-1 expression, suggesting that mutant-IDH1 can change glucose metabolism in cancer cells. Patients with abnormal IDH1 and HIF1 levels were more likely to have a poor prognosis. Further, we identified several risk factors that can influence IDH1 mutations, including cytogenesis, NMP1 mutation status, and ethnicity. The researchers calculated that IDH1 mutations are a significant factor in predicting outcomes for AML.

Paired Transcriptomic Analyses of Atheromatous and Control Vessels Reveal Novel Autophagy and Immunoregulatory Genes in Peripheral Artery Disease.

Peripheral artery disease (PAD), a significant health burden worldwide, affects lower extremities due to atherosclerosis in peripheral vessels. Although the mechanisms of PAD have been well studied, the molecular milieu of the plaques localized within peripheral arteries are not well understood. Thus, to identify PAD-lesion-specific gene expression profiles precluding genetic, environmental, and dietary biases, we studied the transcriptomic profile of nine plaque tissues normalized to non-plaque tissues from the same donors. A total of 296 upregulated genes, 274 downregulated genes, and 186 non-coding RNAs were identified. STAG1, SPCC3, FOXQ1, and E2F3 were key downregulated genes, and CD93 was the top upregulated gene. Autophagosome assembly, cellular response to UV, cytoskeletal organization, TCR signaling, and phosphatase activity were the key dysregulated pathways identified. Telomerase regulation and autophagy were identified as novel interacting pathways using network analysis. The plaque tissue was predominantly composed of immune cells and dedifferentiated cell populations indicated by cell-specific marker-imputed gene expression analysis. This study identifies novel genes, non-coding RNAs, associated regulatory pathways, and the cell composition of the plaque tissue in PAD patients. The autophagy and immunoregulatory genes may drive novel mechanisms, resulting in atheroma. These novel interacting networks and genes have potential for PAD-specific therapeutic applications.

Low-Voltage Area Ablation in Addition to Pulmonary Vein Isolation in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Low-voltage area (LVA) ablation, in addition to pulmonary vein isolation (PVI), has been proposed as a new strategy in patients with atrial fibrillation (AF), but clinical trials have shown conflicting results. We performed a systematic review and meta-analysis to assess the impact of LVA ablation in patient undergoing AF ablation (PROSPERO-registered CRD42024537696). Methods: Randomized clinical trials investigating the role of LVA ablation in addition to PVI in patients with AF were searched on PubMed, Embase, and the Cochrane Library from inception to 22 April 2024. Primary outcome was atrial arrhythmia recurrence after the first AF ablation procedure. Secondary endpoints included procedure time, fluoroscopy time, and procedure-related complication rate. Sensitivity analysis including only patients with LVA demonstration at mapping and multiple subgroups analyses were also performed. Results: 1547 patients from 7 studies were included. LVA ablation in addition to PVI reduced atrial arrhythmia recurrence (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52-0.81, p < 0.001) with a number needed to treat to prevent recurrence of 10. No difference in procedure time (mean difference [MD] -5.32 min, 95% CI -19.01-8.46 min, p = 0.45), fluoroscopy time (MD -1.10 min, 95% CI -2.48-0.28 min, p = 0.12) and complication rate (OR 0.81, 95% CI 0.40-1.61, p = 0.54) was observed. Consistent results were demonstrated when considering only patients with LVA during mapping and in prespecified subgroups for AF type (paroxysmal vs. persistent), multicentric vs. monocentric trial, and ablation strategy in control group. Conclusions: In patients with AF, ablation of LVAs in addition to PVI reduces atrial arrhythmia recurrence without a significant increase in procedure time, fluoroscopy time, or complication rate.

A Meta-Analysis of Surgical Outcomes in 25727 Patients Undergoing Anterior Cervical Discectomy and Fusion or Anterior Cervical Corpectomy and Fusion for Cervical Deformity.

STUDY DESIGN: Systematic Review. OBJECTIVES: To evaluate which cervical deformity correction technique between anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) produces better clinical, radiographic, and operative outcomes. METHODS: We conducted a meta-analysis comparing studies involving ACDF and ACCF. Adult patients with either original or previously treated cervical spine deformities were included. Two independent reviewers categorized extracted data into clinical, radiographic, and operative outcomes, including complications. Clinical assessments included patient-reported outcomes; radiographic evaluations examined C2-C7 Cobb angle, T1 slope, T1-CL, C2-7 SVA, and graft stability. Surgical measures included surgery duration, blood loss, hospital stay, and complications. RESULTS: 26 studies (25727 patients) met inclusion criteria and were extracted. Of these, 14 studies (19077 patients) with low risk of bias were included in meta-analysis. ACDF and ACCF similarly improve clinical outcomes in terms of JOA and NDI, but ACDF is significantly better at achieving lower VAS neck scores. ACDF is also more advantageous for improving cervical lordosis and minimizing the incidence of graft complications. While there is no significant difference between approaches for most surgical complications, ACDF is favorable for reducing operative time, intraoperative blood loss, and length of hospital stay. CONCLUSIONS: While both techniques benefit cervical deformity patients, when both techniques are feasible, ACDF may be superior with respect to VAS neck scores, cervical lordosis, graft complications and certain perioperative outcomes. Further studies are recommended to address outcome variability and refine surgical approach selection.

Effectiveness of deep brain stimulation on refractory aggression in pediatric patients with autism and severe intellectual disability: meta-analytic review.

Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID).Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator's bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies' quality and level of bias.Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators.Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.

Transcatheter Aortic Valve Replacement in Low Surgical Risk Patients: An Updated Metanalysis of Extended Follow-Up Randomized Controlled Trials.

The long-term safety and effectiveness of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) in low surgical risk has not been evaluated in a pooled analysis. An electronic database search was conducted for randomized controlled trials with a maximal 5 years clinical and echocardiographic follow-up including low surgical risk patients who underwent TAVR or SAVR. We calculated odds ratio (OR) and 95% confidence intervals (CIs) using a random-effects model. Subgroups analysis was performed for permanent pacemaker implantation and paravalvular leaks. Three randomized controlled trials were included with a total of 2,611 low surgical risk patients (Society of Thoracic Surgeons score <4%). Compared with SAVR, the TAVR group had similar rates of all-cause mortality (OR 0.94,95% CI 0.65 to 1.37, p = 0.75) and disabling stroke (OR 0.84, 95% CI 0.52 to 1.36, p = 0.48). No significant differences were registered in the TAVR group in terms of major cardiovascular events (OR 0.96, 95% CI 0.67 to 1.38, p = 0.83), myocardial infarction (OR 0.69, 95% CI 0.34 to 1.40, p = 0.31), valve thrombosis (OR 3.11, 95% CI 0.29 to 33.47, p = 0.35), endocarditis (OR 0.71,95% CI 0.35 to 1.48, p = 0.36), aortic valve reintervention (OR 0.93, 95% CI 0.52 to 1.66, p = 0.80), and rehospitalization (OR 0.80, 95% CI 0.52 to 1.02, p = 0.07) compared with SAVR. However, TAVR patients had a higher risk of paravalvular leaks (OR 8.21, 95% CI 4.18 to 16.14, p <0.00001), but lower rates of new-onset atrial fibrillation (OR 0.27,95% CI 0.17 to 0.30, p <0.0001). The rates of permanent pacemaker implantation were comparable from 1 year up to a maximum of 5 years (OR 1.32, 95% CI 0.88 to 1.97, p = 0.18). Lastly, TAVR had a greater effective orifice area (0.10 cm2/m2, 95% CI 0.05 to 0.15, p = 0.0001), but similar transvalvular mean gradients (0.60, 95% CI 3.94 to 2.73, p = 0.72). In conclusion, TAVR patients had similar long-term outcomes compared with SAVR, except for an elevated risk of paravalvular leaks in the TAVR group and increased rates of atrial fibrillation in the SAVR cohort.

Total laryngectomy vs. non-surgical organ preservation in advanced laryngeal cancer: a metanalysis.

OBJECTIVE: To compare the oncological results and the functional outcomes of patients undergoing Total Laryngectomy (TL) with the non-surgical treatment (organ preservation protocol) in the treatment of advanced laryngeal carcinomas through systematic review and meta-analysis. METHODS: A literature survey strategy was employed in order to perform a systematic review of the available evidence. Success rate and functional outomes after oncological treatment of patients with advanced laryngeal carcinomas was evaluated through systematic review and metanalysis, comparing TL and organ preservation protocol. RESULTS: The surgical treatment was associated with better survival outcomes. When stratifying by T stage, while patients with T4 staging have less risk of mortality with TL, there is no difference between the different treatments for patients with T3 tumors. Surgery is related to a lower chance of recurrence, late dysphagia and feeding tube dependence. CONCLUSION: Patients with T4 tumors should undergo TL as their treatment of choice. For patients with T3 tumors, there is no differences on the risk of mortality according to the therapeutic option, however, there is a greater chance of recurrence and dysphagia when surgery is not performed.

Unveiling the SOD1-mediated ALS phenotype: insights from a comprehensive meta-analysis.

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis associated with mutations in SOD1 (SOD1-ALS) might be susceptible to specific treatment. The aim of the study is to outline the clinical features of SOD1-ALS patients by comparing them to patients without ALS major gene variants and patients with variants in other major ALS genes. Defining SOD1-ALS phenotype may assist clinicians in identifying patients who should be prioritized for genetic testing. METHODS: We performed an extensive literature research including original studies which reported the clinical features of SOD1-ALS and at least one of the following patient groups: C9ORF72 hexanucleotide repeat expansion (C9-ALS), TARDBP (TARDBP-ALS), FUS (FUS-ALS) or patients without a positive test for a major-ALS gene (N-ALS). A random effects meta-analytic model was applied to clinical data extracted encompassing sex, site and age of onset. To reconstruct individual patient survival data, the published Kaplan-Meier curves were digitized. Data were measured as odds ratio (OR) or standardized mean difference (SMD) as appropriate. Median survival was compared between groups. RESULTS: Twenty studies met the inclusion criteria. We identified 721 SOD1-ALS, 470 C9-ALS, 183 TARDBP-ALS, 113 FUS-ALS and 2824 N-ALS. SOD1-ALS showed a higher rate of spinal onset compared with N-ALS and C9-ALS (OR = 4.85, 95% CI = 3.04-7.76; OR = 10.47, 95% CI = 4.32-27.87) and an earlier onset compared with N-ALS (SMD = - 0.45, 95% CI = - 0.72 to - 0.18). SOD1-ALS had a similar survival compared with N-ALS (p = 0.14), a longer survival compared with C9-ALS (p < 0.01) and FUS-ALS (p = 0.019) and a shorter survival compared with TARDBP-ALS (p < 0.01). DISCUSSION: This study indicates the presence of a specific SOD1-ALS phenotype. Insights in SOD1-ALS clinical features are important in genetic counseling, disease prognosis and support patients' stratification in clinical trials.

Prevalence of Non-alcoholic Fatty Liver Disease in Iran: A Systematic Review and Meta-analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) has a benign course in several patients; however, a serious form of this disease can turn into liver failure, liver cirrhosis, and hepatocellular carcinoma. Aim: This study aims to estimate the prevalence of NAFLD in Iran. Method: We searched the following databases from January 2000 to December 2022: Scopus, Pubmed/Medline, Embase, Web of Sciences, the Cochrane Library, and Google Scholar also a number of Iranian databases, namely MagIran, SID, and Elmnet. Additionally, the quality of the included studies was evaluated through the Newcastle-Ottawa Scale. We estimated heterogeneity between studies using the I2 statistic. Furthermore, we performed a synthesis of prevalence estimates through the random-effects DerSimonian and Laird model across the included studies with a 95% confidence interval. To assess the publication bias, we also used Egger's test. Results: Thirty-one studies were eligible for inclusion. The overall number of participants in the present study was 41,971. The overall prevalence of NAFLD in Iran was 33% [CI: 27-37%], with I2 = 99.7% (P < 0.01). The prevalence was 35% [CI: 27-43%] and 37% [CI: 27-47%] in males and females, respectively. We used Egger's test, and no significant publication bias was identified in the overall prevalence (P = 0.45). Conclusion: According to the results of this study, the prevalence of NAFLD in Iran is not only high but alsoa growing trend. Effective strategies for changing lifestyles, changing eating habits, and encouraging physical activities among Iranians are recommended. Also, providing screening tests, especially among high-risk groups, has a significant effect on early diagnosis and NAFLD control.

Total laryngectomy vs. non-surgical organ preservation in advanced laryngeal cancer: a metanalysis

Abstract Objective To compare the oncological results and the functional outcomes of patients undergoing Total Laryngectomy (TL) with the non-surgical treatment (organ preservation protocol) in the treatment of advanced laryngeal carcinomas through systematic review and meta-analysis. Methods A literature survey strategy was employed in order to perform a systematic review of the available evidence. Success rate and functional outomes after oncological treatment of patients with advanced laryngeal carcinomas was evaluated through systematic review and metanalysis, comparing TL and organ preservation protocol. Results The surgical treatment was associated with better survival outcomes. When stratifying by T stage, while patients with T4 staging have less risk of mortality with TL, there is no difference between the different treatments for patients with T3 tumors. Surgery is related to a lower chance of recurrence, late dysphagia and feeding tube dependence. Conclusion Patients with T4 tumors should undergo TL as their treatment of choice. For patients with T3 tumors, there is no differences on the risk of mortality according to the therapeutic option, however, there is a greater chance of recurrence and dysphagia when surgery is not performed.

Systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of non-surgical periodontal treatment in patients with concurrent systemic conditions.

OBJECTIVE: To conduct a systematic review of the published scientific evidence to evaluate the efficacy of nonsurgical periodontal therapy (NSPT) in treating periodontitis in patients with concurrent systemic conditions (diabetes, CVD, erectile dysfunction, chronic kidney disease, rheumatoid arthritis, polycystic ovarian syndrome, obesity, pregnancy). We hypothesised that NSPT results in better periodontal outcomes when compared to untreated controls after follow-up. MATERIALS AND METHODS: A systematic search (PUBMED/EMBASE) was conducted from 1995 to 2023 to identify randomised controlled trials (RCTs) with a minimum follow-up of 3 months. The primary outcome was the difference in mean probing depth (PD), and the secondary outcomes were mean clinical attachment loss (CAL), percentage of sites with PD ≤ 3 mm (%PD ≤ 3 mm) and percentage of sites with bleeding on probing (%BOP) between the treated and untreated control group in patients with comorbidities. RESULTS: The electronic search resulted in 2,403 hits. After removing duplicates, 1,565 titles and abstracts were screened according to the eligibility criteria, resulting in 126 articles for full-text screening. Following this, 44 studies were analysed. Restricting to studies with low bias or some concerns, NSPT group demonstrated a 0.55 mm lower mean PD (95%CI: -0.69; -0.41) after 3 months compared to the control group. CONCLUSION: Compared to the untreated controls, NSPT notably reduced mean PD, mean CAL, and %BOP while increasing %PD ≤ 3 mm in patients with concurrent systemic conditions. These findings suggest that NSPT is also an effective procedure in managing periodontitis in patients with concurrent systemic conditions. TRIAL REGISTRATION: This systematic review was registered under the protocol registration number CRD42021241517/PROSPERO.

An Update on the Efficacy of Single and Serial Intravenous Ketamine Infusions and Esketamine for Bipolar Depression: A Systematic Review and Meta-Analysis.

Ketamine has shown rapid antidepressant and anti-suicidal effects in treatment-resistant depression (TRD) with single and serial intravenous (IV) infusions, but the effectiveness for depressive episodes of bipolar disorder is less clear. We conducted an updated systematic review and meta-analysis to appraise the current evidence on the efficacy and tolerability of ketamine/esketamine in bipolar depression. A search was conducted to identify randomized controlled trials (RCTs) and non-randomized studies examining single or multiple infusions of ketamine or esketamine treatments. A total of 2657 articles were screened; 11 studies were included in the systematic review of which 7 studies were included in the meta-analysis (five non-randomized, N = 159; two RCTs, N = 33) with a mean age of 42.58 ± 13.1 years and 54.5% females. Pooled analysis from two RCTs showed a significant improvement in depression symptoms measured with MADRS after receiving a single infusion of ketamine (1-day WMD = -11.07; and 2 days WMD = -12.03). Non-randomized studies showed significant response (53%, p < 0.001) and remission rates (38%, p < 0.001) at the study endpoint. The response (54% vs. 55%) and remission (30% vs. 40%) rates for single versus serial ketamine infusion studies were similar. The affective switch rate in the included studies approximated 2.4%. Esketamine data for bipolar depression are limited, based on non-randomized, small sample-sized studies. Further studies with larger sample sizes are required to strengthen the evidence.

The Effects of Non-Pharmacological Interventions in Fibromyalgia: A Systematic Review and Metanalysis of Predominants Outcomes.

(1) Fibromyalgia (FM) is a chronic musculoskeletal condition with multiple symptoms primarily affecting women. An imbalance in cytokine levels has been observed, suggesting a chronic low-grade inflammation. The main aim of the meta-analysis was to examine the effect of multimodal rehabilitation on cytokine levels and other predominant variables in patients with FM. Furthermore, to examine which non-pharmacological tools have been used to investigate the effects that these can have on cytokines in FM patients. (2) Methods: Searches were conducted in PubMed, Scopus, Web of Science, Cochrane, and ScienceDirect databases. This systematic review and metanalysis followed the PRISMA statement protocol. The methodological quality of the studies was assessed using the PEDro scale, the risk of bias followed the Cochrane Manual 5.0.1, and the GRADE system was used for rating the certainty of evidence. (3) Results: Of 318 studies found, eight were finally selected, with a sample size of 320 women with a mean age of 57 ± 20. The proinflammatory cytokines IL-1ß, IL-6, IL-8 and TNF-α were the most studied. Resistance exercise, aquatic exercise, dynamic contractions, cycling, treadmill, and infrared therapy were the main non-pharmacological tools used. (4) Conclusions: The systematic review with meta-analysis found evidence of elevated cytokine levels in patients with FM, suggesting low chronic inflammation and a possible contribution to central sensitization and chronic pain. However, the effects of physiotherapeutic interventions on cytokine levels are variable, highlighting the importance of considering different factors and the need for further research.

Total Antioxidant Capacity in Obese and Non-Obese Subjects and Its Association with Anthropo-Metabolic Markers: Systematic Review and Meta-Analysis.

The total antioxidant capacity (TAC) has been related to the development of and complications associated with chronic diseases, but its importance during obesity is not entirely clear. We conducted a systematic review and meta-analysis to clarify whether there are differences or similarities in the TAC between subjects with obesity (SO) and subjects with normal weight (NW). Following the recommendations of PRISMA and Cochrane, we performed a systematic search in the PubMed, Scopus, Web of Science, Cochrane, and PROSPERO databases, identifying 1607 studies. Among these, 22 studies were included in the final analysis, comprising 3937 subjects (1665 SO and 2272 NW) in whom serum TAC was measured, and from these 19,201 subjects, the correlation of serum TAC with anthropo-metabolic parameters was also estimated. The Newcastle-Ottawa method was used for the evaluation of the risk of bias. Using a random-effect model (REM), TAC was reduced in SO independently of age (SMD, -0.86; 95% CI -1.38 to -0.34; p = 0.0012), whereas malondialdehyde (SMD, 1.50; 95% CI 0.60 to 2.41), oxidative stress index (SMD, 1.0; 95% CI 0.16 to 1.84), and total oxidant status (SMD, 0.80; 0.22 to 1.37) were increased. There were seven significant pooled correlations of TAC with anthropometric and metabolic parameters: weight (r = -0.17), hip circumference (r= -0.11), visceral adipose index (r = 0.29), triglycerides (r = 0.25), aspartate aminotransferase (r = 0.41), alanine aminotransferase (r = 0.38), and uric acid (r = 0.53). Our results confirm a decrease in TAC and an increase in markers of oxidative stress in SO and underpin the importance of these serum biomarkers in obesity.

A systematic review and metanalysis of questionnaires used for auditory processing screening and evaluation.

The recognition of Auditory Processing Disorder (APD) as a distinct clinical condition that impacts hearing capacity and mental health has gained attention. Although pure tone audiometry is the gold standard for assessing hearing, it inadequately reflects everyday hearing abilities, especially in challenging acoustic environments. Deficits in speech perception in noise, a key aspect of APD, have been linked to an increased risk of dementia. The World Health Organization emphasizes the need for evaluating central auditory function in cases of mild hearing loss and normal audiometry results. Specific questionnaires play a crucial role in documenting and quantifying the difficulties faced by individuals with APD. Validated questionnaires such as the Children's Auditory Processing Performance Scale, the Fisher's Auditory Problems Checklist, and the Auditory Processing Domains Questionnaire are available for children, while questionnaires for adults include items related to auditory functions associated with APD. This systematic review and meta-analysis identified six questionnaires used for screening and evaluating APD with a total of 783 participants across 12 studies. The questionnaires exhibited differences in domains evaluated, scoring methods, and evaluation of listening in quiet and noise. Meta-analysis results demonstrated that individuals with APD consistently exhibited worse scores compared to healthy controls across all questionnaires. Additionally, comparisons with clinical control groups showed varying results. The study highlights (i) the importance of standardized questionnaires in identifying and assessing APD, aiding in its diagnosis and management, and (ii) the need to use sub-scores as well as overall scores of questionnaires to elaborate on specific hearing and listening situations. There is a need to develop more APD specific questionnaires for the adult population as well as for more focused research on APD diagnosed individuals to further establish the validity and reliability of these questionnaires.

How Do Patients With Type 2 Diabetes Mellitus Value the Importance of Outcomes? An Overview of Reviews.

OBJECTIVES: We aimed to assess how patients value the importance of type 2 diabetes mellitus (T2DM) related outcomes. METHODS: Overview of systematic reviews (SRs) reporting patients' utilities or disutilities for T2DM outcomes. We searched 3 databases from inception until June 2021. Study selection and data extraction were conducted in pairs. We evaluated the quality of SRs with the Joanna Briggs Institute Checklist, and the overlap with the corrected covered area. We estimated descriptive statistics, and, when possible, conducted metanalysis. RESULTS: We identified 11 SRs, including 119 studies and 70 outcomes. Most reviews were high-quality SRs. The outcomes with the lowest utilities were hypoglycemia with very severe symptoms (acute complications), stroke (macrovascular complications), diabetic peripheral neuropathy with severe pain (microvascular complications), extreme obesity (comorbidities), and insulin only or combined (management of diabetes). Good/excellent glucose control and noninsulin injectable showed higher values than T2DM without complications. The outcomes with the highest disutilities were amputation, depression, major hypoglycemia, stroke, and management using only insulin. CONCLUSIONS: We provide standardized, reliable utility values (or associated disutilities) for T2DM, acute, microvascular and macrovascular complications, related comorbidities and treatments that may support judgments when making clinical recommendations, designing decision support tools, and developing interventions and economic analysis.