Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma - A Systematic Review and Meta-analysis.

BACKGROUND: Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias. RESULTS: We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved. CONCLUSION: CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.

Improving Diabetic Wound Healing Outcomes with Topical Growth Factor Therapies: Systematic Review and Network Meta-analysis of Randomised-controlled Trials.

CONTEXT: Diabetes mellitus is associated with morbid complications such as diabetic foot ulcers (DFUs) that may lead to amputations or mortality if not managed adequately. OBJECTIVE: New adjunctive interventions to treat diabetic wounds include topical biologics and growth factors. This study aims to evaluate their efficacy in improving wound healing outcomes and safety. DATA SOURCES: Comprehensive database searches of MEDLINE via PubMed, EMBASE and Cochrane performed from inception to December 2022. STUDY SELECTION: Three independent researchers selected the studies. Randomised-controlled trials that compared the use of a topical biologic growth factor-containing regimen to other biologics or standard of care (SOC) were included. DATA EXTRACTION AND SYNTHESIS: This review followed PRISMA guidelines. Risk of bias analysis was performed using the Jadad scale. Network meta-analysis was performed. Treatments were grouped into common nodes based on the type of biologic agent. MAIN OUTCOMES AND MEASURES: Primary outcomes of interest were healing rate and time to wound closure. Secondary outcomes included wound infection, serious adverse events, and amputation rate. RESULTS: Human umbilical cord (HUC) was associated with the highest cure, followed by recombinant human epidermal growth factor (hEGF). A significantly greater reduction in the time to cure DFUs was seen in HUC, hEGF and fibroblast growth factor (FGF). There was a significantly lower risk of adverse events (AEs) when platelet-rich plasma (PRP) was administered. CONCLUSION: HUC, hEGF and FGF are promising topical biologics with statistically significant primary outcomes compared to SOC, while PRP is effective in reducing ulcer-related AEs. HUC has been found to be the most effective in terms of cure rate and a reduction in time to cure.

Cataract Surgery and Cognitive Benefits in the Older Person: A Systematic Review and Meta-analysis.

TOPIC: This systematic review and meta-analysis aims to clarify the association of cataract surgery with cognitive impairment and dementia. CLINICAL RELEVANCE: The association between vision impairment and cognitive decline is well-established. However, the cognitive benefits of cataract surgery are less clear. Given the lack of cure for dementia, identifying modifiable risk factors is key in caring for patients with cognitive deficits. METHODS: The study was conducted following Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. PubMed, Embase, and Cochrane Library were searched from inception through October 11, 2022, for studies reporting the effect of cataract surgery on cognitive impairment and dementia. We pooled maximally adjusted hazard ratios (HRs) for dichotomous outcomes and ratio of means (RoM) for continuous outcomes using a random-effects model. Heterogeneity was examined using sensitivity and subgroup analyses. The quality of evidence was evaluated using the Newcastle-Ottawa scale, Cochrane risk-of-bias tool for randomized trials, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: This review included 24 articles comprising 558 276 participants, of which 19 articles were analyzed qualitatively. The bias of studies ranged from low to moderate, and GRADE extended from very low to low. Cataract surgery was associated with a 25% reduced risk of long-term cognitive decline compared with those with uncorrected cataracts (HR, 0.75; 95% confidence interval [CI], 0.72-0.78). This cognitive benefit was seen across various cognitive outcomes and remained robust to sensitivity analyses. Participants who underwent cataract surgery showed a similar risk of long-term cognitive decline as healthy controls without cataracts (HR, 0.84; 95% CI, 0.66-1.06). Additionally, cataract surgery was associated with a 4% improvement in short-term cognitive test scores among participants with normal cognition (RoM, 0.96; 95% CI, 0.94-0.99), but no significant association was observed among participants with preexisting cognitive impairment. DISCUSSION: Cataract surgery may be associated with a lower risk of cognitive impairment and dementia, and cataract-associated vision impairment may be a modifiable risk factor for cognitive decline. Physicians should be aware of the cognitive sequelae of cataracts and the possible benefits of surgery. The cognitive benefits of cataract surgery should be investigated further in randomized trials. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association of Benign Paroxysmal Positional Vertigo with Depression and Anxiety-A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the extent to which Benign Paroxysmal Positional Vertigo (BPPV) is associated with a higher prevalence of depression and anxiety in patients. DATA SOURCES: Three databases including PubMed, Embase, and The Cochrane Library were searched by two independent authors from inception to June 12, 2022 for observational studies and randomized controlled trials investigating the association between BPPV and depression and anxiety. We included studies published as full-length articles in peer-reviewed journals with an adult population aged at least 18 years who have BPPV, detected through validated clinical methods like clinical diagnosis, interview and Dix-Hallpike test. RESULTS: A total of 23 articles met the final inclusion criteria and 19 articles were included in the meta-analysis. BPPV was associated with a 3.19 increased risk of anxiety compared to controls, and 27% (17%-39%) of BPPV patients suffered from anxiety. Furthermore, the weighted average Beck's Anxiety Inventory score was 18.38 (12.57; 24.18), while the weighted average State-Trait Anxiety Index score was 43.08 (37.57; 48.60). CONCLUSION: There appears to be some association between BPPV and anxiety, but further studies are required to confirm these associations. Laryngoscope, 134:526-534, 2024.

The association of obstructive sleep apnea with blood and cerebrospinal fluid biomarkers of Alzheimer's dementia - A systematic review and meta-analysis.

Alzheimer's disease (AD) is the most common type of dementia and is characterized by the aggregation of extracellular amyloid-beta and intracellular hyperphosphorylation of tau proteins. Obstructive Sleep Apnea (OSA) is associated with increased AD risk. We hypothesize that OSA is associated with higher levels of AD biomarkers. The study aims to conduct a systematic review and meta-analysis of the association between OSA and levels of blood and cerebrospinal fluid biomarkers of AD. Two authors independently searched PubMed, Embase, and Cochrane Library for studies comparing blood and cerebrospinal fluid levels of dementia biomarkers between patients with OSA and healthy controls. Meta-analyses of the standardized mean difference were conducted using random-effects models. From 18 studies with 2804 patients, meta-analysis found that cerebrospinal fluid amyloid beta-40 (SMD:-1.13, 95%CI:-1.65 to -0.60), blood total amyloid beta (SMD:0.68, 95%CI: 0.40 to 0.96), blood amyloid beta-40 (SMD:0.60, 95%CI: 0.35 to 0.85), blood amyloid beta-42 (SMD:0.80, 95%CI: 0.38 to 1.23) and blood total-tau (SMD: 0.664, 95% CI: 0.257 to 1.072, I2 = 82, p<0.01, 7 studies) were significantly higher in OSA patients compared with healthy controls. These findings suggest that OSA is associated with an elevation of some biomarkers of AD.

Efficacy of Anti-PD1 Blockade in Treating Recurrent or Metastatic Nasopharyngeal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVES: Anti-PD1 antibody has emerged as a promising immunotherapeutic option in patients with recurrent and/or metastatic nasopharyngeal cancers (RM-NPC). We aim to summarise existing evidence on the use of anti-PD1 antibodies in the treatment of these patients and compare its effectiveness with standard-of-care palliative chemotherapy. Our secondary aim is to explore potential combination therapies with anti-PD1 antibodies. MATERIALS AND METHODS: PubMed, Embase and Cochrane databases were systematically searched for studies comparing the efficacy of various anti-PD1 antibodies in the treatment of RM-NPC (either as first or second line treatment) from inception to 2 September 2022. Meta-analyses were performed to correlate the various anti-PD1 antibodies with primary endpoints including overall response rate disease control rate (DCR), progression free survival (PFS) and overall survival (OS). RESULTS: Eighteen studies with 1,887 patients met the inclusion criteria. The use of anti-PD1 antibody monotherapy as second-line treatment of RM-NPC revealed an ORR of 23 % (95 % CI = 19 %-28 %) and DCR of 51 % (95 % CI = 42 %-60 %). The ORRs for first-line as well as a combination of first and second-line treatments were 21 % (95 % CI = 15 % - 30 %) and 22 % (95 % CI = 6 % - 56 %, I2 = 75 %) respectively. The 12-month PFS and 12-month OS was also 27 % (95 % CI = 21 %-33 %) and 63 % (95 % CI = 53 %-72 %) respectively. ORR was much higher at 73 % (95 % CI = 32 %-94 %) when anti-PD1 antibodies were combined with Gemcitabine plus Cisplatin. CONCLUSION: Anti-PD1 antibody demonstrate considerable activity in previously treated RM-NPC patients. Combining anti-PD1 antibodies with gemcitabine and cisplatin chemotherapy enhanced the efficacy of treatment.

Association of Hearing Aids and Cochlear Implants With Cognitive Decline and Dementia: A Systematic Review and Meta-analysis.

Importance: Hearing loss is associated with cognitive decline. However, it is unclear if hearing restorative devices may have a beneficial effect on cognition. Objective: To evaluate the associations of hearing aids and cochlear implants with cognitive decline and dementia. Data Sources: PubMed, Embase, and Cochrane databases for studies published from inception to July 23, 2021. Study Selection: Randomized clinical trials or observational studies published as full-length articles in peer-reviewed journals relating to the effect of hearing interventions on cognitive function, cognitive decline, cognitive impairment, and dementia in patients with hearing loss. Data Extraction and Synthesis: The review was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) reporting guidelines. Two authors independently searched the PubMed, Embase, and Cochrane databases for studies relating to the effect of hearing interventions on cognitive decline and dementia in patients with hearing loss. Main Outcomes and Measures: Maximally adjusted hazard ratios (HRs) were used for dichotomous outcomes and ratio of means for continuous outcomes. Sources of heterogeneity were investigated using sensitivity and subgroup analyses, and publication bias was assessed using visual inspection, the Egger test, and trim and fill. Results: A total of 3243 studies were screened; 31 studies (25 observational studies, 6 trials) with 137 484 participants were included, of which 19 (15 observational studies, 4 trials) were included in quantitative analyses. Meta-analysis of 8 studies, which had 126 903 participants, had a follow-up duration ranging from 2 to 25 years, and studied long-term associations between hearing aid use and cognitive decline, showed significantly lower hazards of any cognitive decline among hearing aid users compared with participants with uncorrected hearing loss (HR, 0.81; 95% CI, 0.76-0.87; I2 = 0%). Additionally, meta-analysis of 11 studies with 568 participants studying the association between hearing restoration and short-term cognitive test score changes revealed a 3% improvement in short-term cognitive test scores after the use of hearing aids (ratio of means, 1.03; 95% CI, 1.02-1.04, I2 = 0%). Conclusions and Relevance: In this meta-analysis, the usage of hearing restorative devices by participants with hearing loss was associated with a 19% decrease in hazards of long-term cognitive decline. Furthermore, usage of these devices was significantly associated with a 3% improvement in cognitive test scores that assessed general cognition in the short term. A cognitive benefit of hearing restorative devices should be further investigated in randomized trials.

Improved Inflammatory and Cardiometabolic Profile After Soft-Tissue Sleep Surgery for Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.

Importance: Obstructive sleep apnea (OSA) is associated with a rise in serum inflammatory markers, which may be attenuated by sleep surgery. Objective: To evaluate whether sleep surgery was associated with improved levels of proinflammatory markers in adults with OSA. Data Sources: Two authors independently searched Cochrane, Embase, and PubMed databases from inception through June 14, 2022. Study Selection: Two authors searched the Cochrane, Embase, and PubMed databases for studies comparing preoperative and postoperative levels of serum biomarkers in patients undergoing sleep surgery. Data Extraction and Synthesis: Data were extracted from included articles into a structured proforma. Meta-analyses of the standardized mean difference (SMD) were conducted in random-effects models. To ensure relevance to clinicians and patients, the probability of benefit and number needed to treat were calculated for outcomes that demonstrated a statistically significant effect after sleep surgery. Main Outcomes and Measures: The primary outcome was the preoperative and postoperative levels of serum biomarkers in patients undergoing sleep surgery, including C-reactive protein (CRP), glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and interleukin-6 (IL-6). Data analysis was performed from April to May 2022. Results: Of the 3218 studies screened, 26 studies with 1187 patients (mean [SD] age, 42.8 [11.1] years; 932 [78.5%] men and 255 [21.5%] women) were included. Soft-tissue sleep surgery was associated with a large decrease in CRP (SMD, -0.377; 95% CI, -0.617 to -0.137), total cholesterol (SMD, -0.267; 95% CI, -0.417 to -0.116), LDL (SMD, -0.201; 95% CI, -0.344 to -0.058), IL-6 (SMD, -1.086; 95% CI, -1.952 to -0.221), tumor necrosis factor-α (SMD, -0.822; 95% CI, -1.617 to -0.027), triglyceride (SMD, -0.186; 95% CI, -0.301 to -0.071), and leptin (SMD, -0.519; 95% CI, -0.954 to -0.083) in patients with OSA. Meta-regression highlighted that increased age, higher preoperative score for cumulative sleep time percentage with oxyhemoglobin saturation less than 90% (CT90), and greater change in CT90 postoperatively were associated with a greater decrease in serum CRP levels after soft-tissue sleep surgery. A greater reduction in apnea hypopnea index (AHI) was strongly associated with a greater reduction in total cholesterol and LDL. A greater reduction in body mass index and AHI were also associated with a greater increase in HDL. Conclusions and Relevance: The findings of this systematic review and meta-analysis of 26 studies suggest that sleep surgery is associated with decreased levels of CRP, total cholesterol, LDL, triglyceride, IL-6, leptin, and TNF-α, which may improve the inflammatory and cardiometabolic profile of patients who undergo sleep surgery.

Trainee participation does not adversely affect the safety of thyroid surgery: Systematic review and meta-analysis.

Surgical traineeship is essential but must be safe for patients. In thyroid surgery, surgeon volume correlates with improved clinical/economic outcomes. However, it is presently unclear how far does trainee participation affect post-thyroidectomy complication rates in real-world and randomized data. We systematically searched four databases for associations of trainee participation with any post-thyroidectomy outcome. We conducted univariate meta-analyses, sensitivity analyses, and assessed publication bias qualitatively and quantitatively. We included 1 randomized and 15 observational studies from 3755 records, comprising 34 774 thyroid surgical patients. Trainee participation was associated with 12 min longer operative time, but not higher complication rates (hypoparathyroidism, recurrent laryngeal nerve palsy, hematoma, blood loss, return to operating room, hospitalization duration, readmission, and mortality). Sensitivity, publication bias, and multivariate analyses did not change our findings. Real-world and limited randomized data suggest that trainee participation in thyroid surgery is safe, given adequate consultant supervision and appropriate case selection.