Effectiveness of synthetic versus autologous bone grafts in foot and ankle surgery: a systematic review and meta-analysis.

BACKGROUND: All orthopaedic procedures, comprising foot and ankle surgeries, seemed to show a positive trend, recently. Bone grafts are commonly employed to fix bone abnormalities resulting from trauma, disease, or other medical conditions. This study specifically focuses on reviewing the safety and efficacy of various bone substitutes used exclusively in foot and ankle surgeries, comparing them to autologous bone grafts. METHODS: The systematic search involved scanning electronic databases including PubMed, Scopus, Cochrane online library, and Web of Science, employing terms like 'Bone substitute,' 'synthetic bone graft,' 'Autograft,' and 'Ankle joint.' Inclusion criteria encompassed RCTs, case-control studies, and prospective/retrospective cohorts exploring different bone substitutes in foot and ankle surgeries. Meta-analysis was performed using R software, integrating odds ratios and 95% confidence intervals (CI). Cochrane's Q test assessed heterogeneity. RESULTS: This systematic review analyzed 8 articles involving a total of 894 patients. Out of these, 497 patients received synthetic bone grafts, while 397 patients received autologous bone grafts. Arthrodesis surgery was performed in five studies, and three studies used open reduction techniques. Among the synthetic bone grafts, three studies utilized a combination of recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) and beta-tricalcium phosphate (ß-TCP) collagen, while four studies used hydroxyapatite compounds. One study did not provide details in this regard. The meta-analysis revealed similar findings in the occurrence of complications, as well as in both radiological and clinical evaluations, when contrasting autografts with synthetic bone grafts. CONCLUSION: Synthetic bone grafts show promise in achieving comparable outcomes in radiological, clinical, and quality-of-life aspects with fewer complications. However, additional research is necessary to identify the best scenarios for their use and to thoroughly confirm their effectiveness. LEVELS OF EVIDENCE: Level II.

Robotic assisted Total Knee Arthroplasty (TKA) is not associated with increased patient satisfaction: a systematic review and meta-analysis.

PURPOSE: Total knee arthroplasty (TKA) is a common orthopedic surgery, yet postoperative dissatisfaction persists in around 20% of cases. Robotic total knee arthroplasty (rTKA) promises enhanced precision, but its impact on patient satisfaction compared to conventional TKA remains controversial (cTKA). This systematic review aims to evaluate patient satisfaction post-rTKA and compare outcomes with cTKA. METHODS: Papers from the following databases were identified and reviewed: PubMed, Scopus, Web of Science, and the Cochrane Online Library, using keywords like "Knee replacement," "Total knee arthroplasty," "Robotic," and "Patient satisfaction." Extracted data included patient satisfaction measures, Knee Society Score, Oxford Knee Score, Forgotten Joint Score, SF-36, HSS, and KOOS. Statistical analysis, including odds ratio and 95% CI was performed using R software. Heterogeneity was assessed using Cochrane's Q test. RESULTS: The systematic review included 17 articles, involving 1148 patients (571 in the rTKA group and 577 in the cTKA group) assessing patient satisfaction following rTKA. An analysis of proportions reveals rTKA satisfaction rate was 95%, while for cTKA, it was 91%. A meta-analysis comparing rTKA and cTKA found no statistically significant difference in patient satisfaction. Additionally, various patient-reported outcome measures (PROMs) were examined, showing mixed results across different studies and follow-up periods. CONCLUSIONS: The results of this study found no difference in patient satisfaction outcomes in the short to mid-term for rTKA compared to conventional methods. This study does not assert superiority for the robotic approach, highlighting the need for careful consideration of various factors influencing outcomes in knee arthroplasty.

Behavioral and dysexecutive variant of Alzheimer's disease: Insights from structural and molecular imaging studies.

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aß deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.

Antibiotic-Coated Intramedullary Nailing Managing Long Bone Infected Non-Unions: A Meta-Analysis of Comparative Studies.

Long bone infected non-unions are such an orthopedic challenge that antibiotic-coated intramedullary nailing (ACIN) has become a viable therapeutic option for their management. This study aims to provide a comprehensive assessment of the available data about the use of antibiotic-coated nailing in the treatment of long bone infected non-unions. Following the PRISMA guideline in this meta-analysis, a systematic literature search was conducted across major databases for studies evaluating ACIN in long bone infected non-unions. The primary outcome measures included union rates, infection control, complications and functional status. Five eligible studies encompassing 183 patients in total met the inclusion criteria. The meta-analysis revealed no difference in the union rate in the antibiotic-coated intramedullary nailing group compared to that of the control group (OR = 1.73 [0.75-4.02]). Antibiotic-coated intramedullary nailing demonstrated no association with higher infection eradication (OR = 2.10 [0.97-4.54]). Also, functional outcome measure was mostly not significantly different between ACIN and control interventions. According to this meta-analysis, compared to the management of controls, ACIN is neither linked to increased union rates nor decreased infection rates. The paucity of research on this topic emphasizes the continuous need for additional well-designed randomized controlled trials for the application of antibiotics-coated intramedullary nailing in long bone non-unions.

T1 and T2 weighted lesions and cognition in multiple Sclerosis: A systematic review and meta-analysis.

BACKGROUND: Considering the different results regarding the correlation between Magnetic Resonance Imaging (MRI) structural measures and cognitive dysfunction in patients with MS, we aimed to perform a systematic review and meta-analysis study to investigate the correlation between T1 and T2 weighted lesions and cognitive scores to find the most robust MRI markers for cognitive function in MS population. METHODS: The literature of this paper was identified through a comprehensive search of electronic datasets including PubMed, Scopus, Web of Science, and Embase in February 2022. Studies that reported the correlation between cognitive status and T1 and T2 weighted lesions in MS patients were selected. RESULTS: 21 studies with a total of 3771 MS patients with mean ages ranging from 30 to 57 years were entered into our study. Our analysis revealed that the volume of T1 lesions was significantly correlated with Symbol Digit Modality test (SDMT) (r: -0.30, 95 %CI: -0.59, -0.01) and Paced Auditory Serial-Addition Task (PASAT) scores (r: -0.23, 95 %CI: -0.36, -0.10). We investigated the correlation between T2 lesions and cognitive scores. The pooled estimates of z scores were significant for SDMT (r: -0.27, 95 %CI: -0.51, -0.03) and PASAT (r: -0.27, 95 %CI: -0.41, -0.13). CONCLUSION: In conclusion, our systematic review and meta-analysis study provides strong evidence of the correlation between T1 and T2 lesions and cognitive function in MS patients. Further research is needed to explore the potential mechanisms underlying this relationship and to develop targeted interventions to improve cognitive outcomes in MS patients.

Suicidality risk after using cannabis and cannabinoids: An umbrella review.

The increasing prevalence and burden of suicide have led to numerous studies to identify its risk factors. Cannabis is the most common illicit substance detected in suicide victims' toxicology tests. This study aims to identify and appraise systematic reviews investigating suicidality after using cannabis and cannabinoids. Seven databases and two registries were searched without restrictions for systematic reviews investigating cannabis effects on suicidality. AMSTAR-2 was used for quality assessment and corrected covered area and citation matrix were used to determine overlap. Twenty-five studies were included, of which 24 were on recreational use and one was on therapeutic use. Only three of the studies on recreational use reported no effect or inconsistent results. Evidence generally showed a positive association between cannabis use and suicidal ideation and attempt among the general population, military veterans, and bipolar or major depression patients. A bidirectional causal association between cannabis and suicidal ideation was also mentioned. Moreover, a younger age of initiation, long-term use, and heavy consumption were reported to be associated with even worse suicidal outcomes. On the contrary, current evidence indicates that the therapeutic cannabis is safe. In conclusion, the literature supports the cannabis-suicidality association in recreational use but considers cannabidiol safe for treatment. Further studies with quantitative and interventional approaches are recommended.

Optimal method for ablation of atypical AVNRT.

BACKGROUND: Considering that ablation of atypical AVNRT may be unsuccessful after ablation at the right posterior septum, in this study, we aimed to present an optimal method for ablation of atypical AVNRT. Also, we evaluated the efficacy of this technique for preventing recurrences. METHODS: This is a prospective, double-center study. It was conducted on 62 patients with atypical AVNRT referred for radiofrequency ablation. The patients were randomly divided into two groups before ablation: 1-Group A (n = 30): treated with conventional ablation at the anatomic area of the slow pathway; 2-Group B (n = 32): ablation was done 2 mm higher in the septum during fluoroscopy. RESULTS: The mean age of patients in groups A and B were 54 ± 11.7 and 55 ± 12.2, respectively (P = 0.43). In group A, ablation was successful in 24 (80%) patients following right-sided slow pathway ablation, and the remaining patients required further treatment with either a left-side approach (N = 4, 13.3%) or ablation of additional regions (N = 2, 6.7%). In group B, ablation was successful in all patients. After a 48-month follow-up, recurrence of symptomatic atypical AVNRT was detected in 4 (13.3%) patients of group A and none of group B patients (p < 0.001). CONCLUSION: In patients with atypical AVNRT, ablation 2 mm above the conventional area is more promising regarding success rate and recurrence of the arrhythmia.

Longitudinal striatal dopamine transporter binding and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau, and phosphorylated tau in Parkinson's disease.

BACKGROUND: Previous studies investigated CSF levels of α-synuclein (α-syn), amyloid-ß (Aß1-42), total tau (t-tau), and phosphorylated tau (p-tau) with clinical progression of Parkinson's disease (PD). However, there is limited data on the association between CSF biomarkers and dopamine uptake status in PD. AIM: In the current study, we aim to investigate the longitudinal association between striatal dopaminergic neuronal loss assessed by dopamine active transporter single photon emission computerized tomography (DaTSCAN) imaging with CSF α-syn, t-tau, p-tau, and Aß1-42. METHODS: A total of 413 early-stage PD patients and 187 healthy controls (HCs) from the PPMI. Striatal binding ratios (SBRs) of DaTSCAN images in caudate and putamen nuclei were calculated. We investigated the cross-sectional and longitudinal association between CSF biomarkers and dopamine uptake using partial correlation models adjusted for the effect of age, sex, and years of education over 24 months of follow-up. RESULTS: The level of CSF α-syn, Aß1-42, t-tau, and p-tau was significantly higher in HCs compared to PD groups at any time point. We found that higher CSF α-syn was associated with a higher SBR score in the left caudate at baseline (P = 0.038) and after 12 months (P = 0.012) in PD patients. Moreover, SBR scores in the left caudate and CSF Aß1-42 were positively correlated at baseline (P = 0.021), 12 months (P = 0.006), and 24 months (P = 0.014) in patients with PD. Our findings demonstrated that change in CSF Aß1-42 was positively correlated with change in SBR score in the left caudate after 24 months in the PD group (P = 0.043). CONCLUSION: We found that cross-sectional levels of α-syn and Aß1-42 could reflect the degree of dopaminergic neuron loss in the left caudate nucleus. Interestingly, longitudinal changes in CSF Aß1-42 could predict the severity of left caudal dopaminergic neuron loss throughout the disease. This suggested that Aß pathology might precede dopaminergic loss in striatal nuclei in this case left caudate and subsequently cognitive impairment in PD patients, although future studies are needed to confirm our results and expand the understanding of the pathophysiology of cognitive dysfunction in PD.

Autologous Hematopoietic Stem-Cell Transplantation in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: In 1995, the use of autologous hematopoietic stem-cell transplantation (AHSCT), which was previously used to treat hematological tumors, was introduced for severe autoimmune diseases such as multiple sclerosis (MS). AHSCT has proven its safety over the past few years due to technical advances and careful patient selection in transplant centers. While most studies have reported that AHSCT led to decreased Expanded Disability Status Scale (EDSS) scores, some patients reported increased EDSS scores following the procedure. Given the contradictory results, we aimed to conduct a comprehensive systematic review and meta-analysis to investigate the efficacy and safety of AHSCT. METHODS: PubMed, Web of Science, and Scopus were searched in March 2022 using a predefined search strategy. We included cohort studies, clinical trials, case-control studies, and case series that investigated the efficacy or safety of AHSCT in patients with MS. PICO in the present study was defined as follows: problem or study population (P): patients with MS; intervention (I): AHSCT; comparison (C): none; outcome (O): efficacy and safety. RESULTS: After a two-step review process, 50 studies with a total of 4831 patients with MS were included in our study. Our analysis showed a significant decrease in EDSS score after treatment (standardized mean difference [SMD]: -0.48, 95% CI -0.75, -0.22). Moreover, the annualized relapse rate was also significantly reduced after AHSCT compared to the pretreatment period (SMD: -1.58, 95% CI -2.34, -0.78). The pooled estimate of progression-free survival after treatment was 73% (95% CI 69%, 77). Furthermore, 81% of patients with MS who received AHSCT remained relapse-free (95% CI 76%, 86%). Investigating event-free survival, which reflects the absence of any disease-related event, showed a pooled estimate of 63% (95% CI 54%, 73%). Also, the MRI activity-free survival was 89% (95% CI 84%) among included studies with low heterogeneity. New MRI lesions seem to appear in nearly 8% of patients who underwent AHSCT (95% CI 4%, 12%). Our meta-analysis showed that 68% of patients with MS experience no evidence of disease activity (NEDA) after AHSCT (95% CI 59%, 77). The overall survival after transplantation was 94% (95% CI 91%, 96%). In addition, 4% of patients died from transplant-related causes (95% CI 2%, 6%). CONCLUSION: Current data encourages a broader application of AHSCT for treating patients with MS while still considering proper patient selection and transplant methods. In addition, with increasing knowledge and expertise in the field of stem-cell therapy, AHSCT has become a safer treatment approach for MS.

Olfactory dysfunction and striatal dopamine transporter binding in motor subtypes of Parkinson's disease.

BACKGROUND: Olfactory dysfunction is one of the earliest non-motor symptoms (NMS) in Parkinson's disease (PD). There are contradictory results regarding the association of olfactory dysfunction and dopamine uptake in striatal nuclei among PD patients. It has been suggested that different motor subtypes of PD vary in the disease pathophysiology and progression. Thus, we hypothesized that there might be different associations between olfactory dysfunction and striatal dopaminergic neuronal loss among three motor subtypes of PD, namely, indeterminate, postural instability and gait difficulty (PIGD), and tremor-dominant (TD). METHODS: We recruited 162 healthy controls (HCs) and 464 drug-naïve PD patients from PPMI who underwent common PD scaling tests. Striatal binding ratios (SBRs) of DaTSCAN images in caudate and putamen nuclei were calculated. To assess the olfactory function, the University of Pennsylvania Smell Identification Test (UPSIT) was carried out. RESULTS: The UPSIT score was significantly correlated with MDS-UPDRS part I (p value: 0.002, correlation coefficient: - 0.160), MDS-UPDRS part III (p value: 0.000, correlation coefficient: - 0.248), and SBR score in right (p value: 0.000, correlation coefficient: 0.240) and left caudate (p value: 0.000, correlation coefficient: 0.221) and right (p value: 0.000, correlation coefficient: 0.323) and left putamen (p value: 0.000, correlation coefficient: 0.335) nucleus in TD subtype. There were no significant correlations in HC, PIGD, and indeterminate subjects. CONCLUSION: The olfactory dysfunction was correlated with dopamine transporter activity in striatal nuclei only in the TD subtype. Therefore, the olfactory dysfunction in PIGD and indeterminate subtype may not be a predictive factor for the future decrease in dopamine uptake.

REM sleep behavior disorder and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau and phosphorylated tau in Parkinson's disease: a cross-sectional and longitudinal study.

BACKGROUND: Proteinopathies as a consequence of cellular pathological pathways associated with Parkinson's disease (PD), leading to alteration of protein aggregation in cerebrospinal fluid (CSF). Rapid eye movement (REM) sleep behavior disorder (RBD is generally accepted as a prognostic factor predicting neurodegeneration, worse cognitive impairment, and the development of dementia PD. AIM: Here we aimed to investigate the difference and longitudinal alteration of the CSF level of α-synuclein (α-syn), amyloid ßeta (Aß1-42), total tau (t-tau), and phosphorylated tau (p-tau) in PD subjects with RBD and without RBD. METHODS: We entered 413 early stage PD patients and 187 healthy controls (HCs) from PPMI. We compared the level of CSF biomarkers at baseline, 6 months, 1 year, and 2 years visits. In addition, we used linear mixed models to assess longitudinal changes of CSF proteins over 6 months, 1 year, and 2 years within groups. RESULTS: The level of CSF α-syn, Aß1-42, t-tau, and p-tau was significantly higher in HCs compared to PD groups at any timepoint. In addition, there was a significantly lower CSF Aß1-42 in PD-RBD subjects at 2 years timepoint (p = 0.020). There was no difference in CSF Aß1-42 at other timepoints. Furthermore, comparisons between PD subjects with RBD and without RBD did not show any significant difference in CSF α-syn, t-tau, and p-tau at timepoints. The longitudinal analysis demonstrated that there was only a significant change in CSF level of Aß1-42 after 1 year in PD patients with RBD (p = 0.031). CONCLUSIONS: In our study, baseline values and longitudinal changes in CSF α-syn, t-tau, and p-tau were not remarkable enough to distinguish PD patients with and without RBD. Both of these groups demonstrated a stable trend in the longitudinal changes of these biomarkers. However, CSF Aß1-42 seems to decrease in short follow-up and represents a significant difference after a while in PD patients with and without RBD. These findings suggested that CSF Aß1-42 could be a more sensitive biomarker for early neurodegeneration and cognitive impairment in PD patients. The stable trend in other CSF biomarkers such as α-syn, t-tau, and p-tau can be justified by the fact that severe neurodegeneration may not be predictable in the early stages of PD patients.

Olfactory dysfunction is associated with motor function only in tremor-dominant Parkinson's disease.

BACKGROUND: The prevalence of olfactory impairment in patients with Parkinson's disease (PD) is 50-90%, and therefore, olfactory dysfunction is one of the most prevalent non-motor symptoms (NMSs) in patients with PD. Numerous studies have evaluated the association between motor and non-motor symptoms and olfactory dysfunction in PD. AIM: In this study, we investigated the relationship between olfactory dysfunction, which is measured using the UPSIT test, with other motor and non-motor symptoms separately in three motor subtypes of PD, including tremor dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate and healthy subjects. METHODS: We recruited 487 early-stage PD patients (43 PIGD, 406 TD, and 38 indeterminate) and healthy controls (HCs) (n = 197) from the Parkinson Progression Markers Initiative (PPMI). All participants completed motor and non-motor tests at baseline visit and after 4 years of follow-up. Subjects underwent common PD scaling tests. RESULTS: Olfactory dysfunction was significantly correlated with declined motor functions only in the TD subtype. Also, significant correlations were noticed between olfactory dysfunction and speed-attention processing and executive function in the HCs as well. Finally, no significant or meaningful association was observed in the PIGD and indeterminate subtype. Anosmia and hyposmia subjects in the TD group had the worse motor and non-motor scores compared to normosmia subjects after 4 years. CONCLUSION: Olfactory dysfunction was significantly correlated with declined motor functions in the TD subtype. This is indicating that olfactory dysfunction may be an early motor and non-motor biomarker only in the TD subtype. However, it is possible that the involvement of olfactory function in other subtypes is not strong enough to make it a useful marker of diseases progression.