Intra-articular Injection of Autologous Adipose-Derived Stem Cells or Stromal Vascular Fractions: Are They Effective for Patients With Knee Osteoarthritis? A Systematic Review With Meta-analysis of Randomized Controlled Trials

Background: Intra-articular injection of adipose-derived stem cells, which are divided into adipose-derived mesenchymal stem cells (ASCs) and adipose-derived stromal vascular fractions (ADSVFs), has been reported to be a viable treatment modality for knee osteoarthritis (OA); however, its efficacy remains limited. Purpose: This study aimed to provide comprehensive information about the efficacy and safety of intra-articular injections of autologous ASCs and ADSVFs without adjuvant treatment in patients with knee OA. Study Design: Meta-analysis; Level of evidence, 1. Methods: A systematic search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of intra-articular injections of autologous ASCs or ADSVFs without adjuvant treatments compared with placebo or hyaluronic acid in patients with knee OA. Clinically, the 100-mm visual analog scale for pain relief and the Western Ontario and McMaster Universities Osteoarthritis Index for functional improvement were implemented. Radiologically, cartilage status was assessed using magnetic resonance imaging (MRI). Procedure-related knee pain, swelling, and adverse events (AEs) were evaluated for safety. Additionally, we performed subgroup analyses comparing ASCs versus ADSVFs. Methodological quality was assessed using the modified Coleman Methodology Score (mCMS). Results: A total of 5 RCTs were included in this study. Based on the meta-analysis, ASCs or ADSVFs showed significantly better pain relief at 6 months ( Z = 7.62; P < .0001) and 12 months ( Z = 7.21; P < .0001) and functional improvement at 6 months ( Z = 4.13; P < .0001) and 12 months ( Z = 3.79; P = .0002), without a difference in procedure-related knee pain or swelling compared with controls. Although a meta-analysis with regard to cartilage improvements was not performed owing to heterogeneous MRI assessment, 3 studies reported significantly improved cartilage status after the injection. No serious AEs associated with ASCs or ADSVFs were reported. Subgroup analyses showed similar efficacy between ASC and ADSVF treatments. The median mCMS was 70 (range, 55-75). Conclusion: For patients with knee OA, intra-articular injection of autologous ASCs or ADSVFs without adjuvant treatment showed remarkable clinical efficacy and safety at short-term follow-up. Some degree of efficacy has been shown for cartilage regeneration in knee OA, although the evidence remains limited. Further RCTs that directly compare ASCs and ADSVFs are needed.

Full-field Electroretinography Changes Associated with Age-related Macular Degeneration: A Systematic Review with Meta-Analyses

Background: To systematically review the literature and to perform meta-analyses on full-field electroretinography (ffERG) between healthy controls and age-related macular degeneration (AMD) to map the extent of retinal dysfunction. Summary: We systematically searched 11 databases on 3 March 2021. Eligible studies had to measure retinal function using ffERG in eyes with AMD and in healthy controls. We extracted data on a-wave and b-wave function in dark- and light-adapted ffERG, and calculated summary estimates on differences between eyes with AMD and controls using weighted mean differences (WMD). Subgroup analyses were made for early and late AMD. Six studies (n=481 eyes) were eligible for review (301 with any AMD, 180 controls). For dark-adapted data, any AMD was associated with reduced a-wave amplitude (WMD: -17.16 µV; 95% CI: -31.79 to -2.52 µV; P=0.02) and b-wave amplitude (WMD: -28.70 µV; 95% CI: -51.40 to -6.01 µV; P=0.01). For light-adapted data, any AMD was associated with longer a-wave implicit time (WMD: 0.92 ms; 95% CI: 0.12 to 1.72 ms; P=0.02), reduced b-wave amplitude (WMD: -13.26 µV; 95% CI: -18.64 to -7.88 µV; P<0.0001), and longer b-wave implicit time (WMD: 0.69 ms; 95% CI: 0.30 to 1.08 ms; P=0.0006). Subgroup analyses found that these changes were only statistically significant in eyes with late AMD, not early AMD. Key messages: Reduced retinal function on ffERG is present in eyes with AMD, in particular those with late AMD. These findings suggest that AMD is a pan-retinal disease with AMD-associated photoreceptor dysfunction beyond the macula.

Association Between Prediabetes and Erectile Dysfunction: A Meta-Analysis

BackgroundDiabetes has been associated with the increased risk of erectile dysfunction (ED). However, previous studies evaluating the association between prediabetes and ED showed inconsistent results. We performed a meta-analysis of observational studies to systematically evaluate the above association.MethodsRelevant observational studies were retrieved by search of PubMed, Embase, and Web of Science databases. A random-effect model which incorporated the potential intra-study heterogeneity was used for the meta-analysis. Subgroup analyses were performed to evaluate the influences of study characteristics on the outcome.ResultsNine studies (five matched case-control studies and four cross-sectional studies) were included. Age were adjusted or matched in all of the studies. Pooled results showed that compared to men with normoglycemia, men with prediabetes were associated with higher prevalence of ED (odds ratio = 1.62, 95% confidence interval: 1.28 to 2.07, P &lt; 0.001; I2 = 78%). Subgroup analyses showed that the association was not significantly affected by definition of prediabetes, diagnostic tool for ED, or controlling of additional variables besides age (both P for subgroup difference &gt; 0.05). However, the association between prediabetes and ED seemed to be stronger in case-control studies than that in cross-sectional studies, and in studies with younger men (mean age &lt; 50 years) than in those with older men (mean age ≥ 50 years; both P for subgroup difference &lt; 0.05).ConclusionsPrediabetes is associated with higher prevalence of ED, which may be independent of age of the males and may be stronger in young men.

Utility of Systemic Inflammatory Syndrome Score in Predicting Healthcare-Associated Infections in Critically Ill Patients: A Matched Case-Control Study

Background Effective prevention of healthcare-associated infections (HAIs) requires early identification of at-risk patients. There is no score designed to predict HAIs. The present study was aimed to explore an available score, Systemic inflammatory syndrome (SIRS) score, on admission in predicting HAIs among critically ill patients. Methods This study was based on the Medical Information Mart for Intensive Care III (MIMIC III) version 1.4. Patients with HAIs were matched with control patients who had no HAIs in a 1:1 ratio based on age, gender, mechanical ventilation, deep venous catheterization, urethral catheterization, and surgical operation. Subgroup analyses were conducted according to various variables including infection likelihood on admission. The prognostic values of SIRS and infectious SIRS on admission in predicting HAIs were analyzed using logistic regression. Results A total of 2437 patients with HAIs and 2437 matched controls were enrolled in the final analysis. Adjusted odds ratio (ORs) (95% confidence interval [CI]) for HAIs of SIRS scores (1 to 4) on admission was 1.48 (0.77-2.83), 1.86 (0.99-3.47), 2.14 (1.15-3.98), and 2.58 (1.39-4.80). Adjusted ORs (95%CI) for HAIs of SIRS (score≥2) and infectious SIRS were 1.57 (1.27-1.94) and 1.78 (1.52-2.09), respectively. Subgroup analyses showed that SIRS on admission was an independent risk factor for HAIs in patients admitted without definite and probable infection likelihood (OR=1.54, 95%CI 1.28-1.93). However, it was not a risk factor for HAIs inpatients admitted with infection, in non-white patients, and in patients with liver disease or obesity, and in patients who received total parenteral nutrition (TPN) (all P>0.05). In addition, it was showed that infectious SIRS on admission was not a risk factor for HAIs in black patients and in patients with obesity, and those received TPN (all P>0.05). Conclusions Infectious SIRS on admission significantly predicts HAIs among critical illness patients. SIRS on admission was a predictor of HAIs in ICU patients admitted without infection but not in patients admitted with infection.

Performance of Rapid Antigen Tests for COVID-19 Diagnosis: A Systematic Review and Meta-Analysis

The identification of viral RNA using reverse transcription quantitative polymerase chain reaction (RT-qPCR) is the gold standard for identifying an infection caused by SARS-CoV-2. The limitations of RT-qPCR such as requirement of expensive instruments, trained staff and laboratory facilities led to development of rapid antigen tests (RATs). The performance of RATs has been widely evaluated and found to be varied in different settings. The present systematic review aims to evaluate the pooled sensitivity and specificity of the commercially available RATs. This review was registered on PROSPERO (registration number: CRD42021278105). Literature search was performed through PubMed, Embase and Cochrane COVID-19 Study Register to search studies published up to 26 August 2021. The overall pooled sensitivity and specificity of RATs and subgroup analyses were calculated. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to assess the risk of bias in each study. The overall pooled sensitivity and specificity of RATs were 70% (95% CI: 69–71) and 98% (95% CI: 98–98), respectively. In subgroup analyses, nasal swabs showed the highest sensitivity of 83% (95% CI: 80–86) followed by nasopharyngeal swabs 71% (95% CI: 70–72), throat swabs 69% (95% CI: 63–75) and saliva 68% (95% CI: 59–77). Samples from symptomatic patients showed a higher sensitivity of 82% (95% CI: 82–82) as compared to asymptomatic patients at 68% (95% CI: 65–71), while a cycle threshold (Ct) value ≤25 showed a higher sensitivity of 96% (95% CI: 95–97) as compared to higher Ct value. Although the sensitivity of RATs needs to be enhanced, it may still be a viable option in places where laboratory facilities are lacking for diagnostic purposes in the early phase of disease.

Efficacy of intrauterine insemination in women with endometrioma-associated subfertility: analysis using propensity score matching

Background Intrauterine insemination (IUI) treatment is recommended in subfertile women with AFS/ASRM stage I/II endometriosis. However, the efficacy of IUI in women with ovarian endometriomas with tubal patency is uncertain. We explored the efficacy of IUI for the treatment of endometrioma-associated subfertility. Methods We performed a retrospective matched cohort study using propensity matching (PSM) analysis. Subfertile couples undergoing IUI with and without ovarian stimulation between January 1, 2015, and May 30, 2020 were reviewed. Results After PSM, 56 women with endometrioma alone were matched to 173 patients with unexplained subfertility. The per-cycle pregnancy rate (PR) was comparable between women with endometrioma-associated subfertility (n = 56, 87 cycles) and women with unexplained subfertility (n = 173, 280 cycles) (9.2% vs. 17.9%, OR 0.47; 95% CI, 0.21–1.03). Subgroup analyses based on IUI with or without stimulation also resulted in comparable results. A trend toward a lower cumulative pregnancy rates (CPRs) was seen in women with endometrioma (14.3%, 8/56) compared with women with unexplained subfertility (28.9%, 50/173), but the differences were not significant (HR 0.49; 95% CI, 0.23–1.15). However, patients with endometrioma were nearly twice as likely to converse to IVF treatment compared with those without the disease (60.7% versus 43.9%; OR 1.97; 95% CI, 1.07–3.65). Conclusion IUI may be a viable approach for subfertile women with endometrioma and no other identifiable infertility factor. More studies are needed to reassure the findings.

Risk Factors for Esophageal Collateral Veins in Cirrhosis with and without Previous Endoscopic Esophageal Variceal Therapy

Background. Portosystemic collateral vessels are a sign of portal hypertension in liver cirrhosis. Esophageal collateral veins (ECVs) are one major type of portosystemic collateral vessels, which increase the recurrence of esophageal varices and bleeding after variceal eradication. However, the risk factors for ECVs were still unclear. Methods. We retrospectively screened cirrhotic patients who had contrast-enhanced computed tomography (CT) images to evaluate ECVs and upper gastrointestinal endoscopic reports to evaluate gastroesophageal varices at our department. Univariate and multivariate logistic regression analyses were performed to explore the independent risk factors for ECVs. Odds ratios (ORs) were calculated. Subgroup analyses were performed in patients with and without previous endoscopic variceal therapy which primarily included endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). Results. Overall, 243 patients were included, in whom the prevalence of ECVs was 53.9%. The independent risk factors for ECVs were hepatitis C virus infection (OR = 0.250, p = 0.026), previous EVL (OR = 1.929, p = 0.044), platelet (OR = 0.993, p = 0.008), and esophageal varices needing treatment (EVNTs) (OR = 2.422, p = 0.006). The prevalence of ECVs was 60.8% (73/120) in patients undergoing EVL, 50% (10/20) in those undergoing EIS, and 47.5% (48/101) in those without previous endoscopic variceal therapy. The independent risk factors for ECVs were the use of nonselective beta-blockers (OR = 0.294, p = 0.042) and EVNTs (OR = 3.714, p = 0.006) in subgroup analyses of patients with and without previous endoscopic variceal therapy, respectively. Conclusions. The presence of ECVs should be closely associated with the severity of portal hypertension in liver cirrhosis. Risk of ECVs might be increased by previous EVL.

Efficacy of ICIs on patients with oncogene-driven non-small cell lung cancer: a retrospective study

Aim: The objective of our study was to assess the efficacy of immune checkpoint inhibitors (ICIs) on patients with non-small-cell lung cancer (NSCLC) harboring oncogenic alterations. Methods: We retrospectively enrolled patients with advanced non-squamous NSCLC who were treated with anti-PD-1-based monotherapy or combined immunotherapy. Major characteristics including PD-L1 expression, treatment, and survival were analyzed. Results: In total, 309 non-squamous NSCLC patients with a median age of 61 years (range 20-88 years) including 70.9% male were retrospectively enrolled. The molecular alterations involved epidermal growth factor receptor (EGFR) (n = 81), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) (n = 31), anaplastic lymphoma kinase (ALK) (n = 1), human epidermal growth factor receptor 2 (HER2) (n = 12), V-raf murine sarcoma viral oncogene homolog (BRAF) (n = 2), rearranged during transfection (n = 4), and c-ros oncogene 1 (ROS1) (n = 3). In the EGFR subset, the ORR was 30.9% (n = 81) and PFS was significantly shorter than WT group (median PFS: 5.7 months vs. 7.1 months; P = 0.0061). In subgroup analyses, ICI combined therapy was significantly correlated with a longer PFS compared with ICI monotherapy (median PFS: 7.7 months vs. 4.7 months; P = 0.0112). In KRAS patients, ORR was 51.6% (n = 31). No significant difference was found in subgroup analyses. The ORR and PFS were 16.7% (n = 12) and 28.6% (n = 7), 7.8 months and 9.0 months for HER2 and EGFR Exon20 insertion patients, respectively. Three ROS1 patients were enrolled with a PFS of 16.0, 34.2, and 45.0 months individually, and one ALK patient with PFS of 4.4 months was identified. No response was found in two BRAF patients. Conclusion: ICI-based combination therapy can bring benefit to patients with EGFR-mutant NSCLC. ICI-based combination therapy could be considered for patients with ROS1 rearrangement, HER2 mutation and EGFR Exon20 insertion NSCLC.

Long-term survival of metastatic small intestine neuroendocrine tumors: a meta-analysis

This meta-analysis aims to evaluate long-term survival and prognostic factors in patients with metastatic small intestine neuroendocrine tumors (siNETs). Patients with siNETs usually present with advanced disease, limiting curative treatment options. Overall survival seems favorable compared to other cancers but differences in terminology, lack of consistent coding, conflicting results from smaller cohorts, and recent developments of new treatment options make (reliable) survival data difficult to achieve. Nevertheless, accurate survival data are essential for many facets of health care. A systematic literature search was performed, using MEDLINE® (PubMed), EMBASE®, Web of Science, and Cochrane Library up to June 30th, 2021. Studies were included if overall survival data in patients with metastatic siNETs were reported. The results were pooled in a random-effects meta-analysis and are reported as hazard ratios and 95% confidence intervals (CIs). Subgroup analyses and meta-regression were performed to assess the observed heterogeneity and the impact of important prognostic factors. After screening 9,065 abstracts there were 23 studies, published between 1995 and 2021, that met the inclusion criteria, with a total of 8,636 patients. The weighted five- and ten-year overall survival was 67% and 37% respectively. Meta-regression identified younger age and primary tumor resection to be associated with better prognosis. Subgroup analyses showed similar results. This study confirms that in an advanced, metastatic setting, the weighted five-year and 10-year overall survival reveal a favorable prognosis, improving over the last few decades. Meta-regression showed that age at diagnosis is an important prognostic factor.

Acupoint stimulation-related therapies for the management of insomnia disorder: A systematic review and meta-analysis protocol

Review question / Objective: This meta-analysis will not only summarize all the ASRTs reported in clinical trials but also evaluate their effect on objective and subjective indices related to insomnia disorder. We will also perform subgroup analyses to identify possible confounders of the effects of ASRTs including treatment characteristics (e.g., acupoint selection, stimulation method, treatment duration) and patient characteristics (e.g., age, comorbidities, severity, and course of insomnia disorder). In doing so, we will endeavor to answer questions about whether efficacy varies according to the aspect of sleep targeted and whether the effects differ according to different modes of acupoint stimulation, acupoints applied, or specific types of insomnia, thereby providing the evidence to develop specific recommendations on prescribing ASRTs for insomnia disorder.