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Survey of Ophthalmology 2024Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly... (Meta-Analysis)
Meta-Analysis Review
Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).
Topics: Humans; Retinal Necrosis Syndrome, Acute; Antiviral Agents; Acyclovir; Eye Infections, Viral; Retinal Detachment; Retrospective Studies
PubMed: 37774799
DOI: 10.1016/j.survophthal.2023.09.004 -
European Respiratory Review : An... Dec 2023Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the first-line treatment but recent reports suggest the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF). We aimed to review the efficacy and safety of nebulised GM-CSF in aPAP.
METHODS
We conducted a systematic review and meta-analysis searching Embase, CINAHL, MEDLINE and Cochrane Collaborative databases (1946-1 April 2022). Studies included patients aged >18 years with aPAP receiving nebulised GM-CSF treatment and a comparator cohort. Exclusion criteria included secondary or congenital pulmonary alveolar proteinosis, GM-CSF allergy, active infection or other serious medical conditions. The protocol was prospectively registered with PROSPERO (CRD42021231328). Outcomes assessed were St George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT), gas exchange (diffusing capacity of the lung for carbon monoxide ( ) % predicted) and arterial-alveolar oxygen gradient.
RESULTS
Six studies were identified for review and three for meta-analysis, revealing that SGRQ score (mean difference -8.09, 95% CI -11.88- -4.3, p<0.0001), functional capacity (6MWT) (mean difference 21.72 m, 95% CI -2.76-46.19 m, p=0.08), gas diffusion ( % predicted) (mean difference 5.09%, 95% CI 2.05-8.13%, p=0.001) and arterial-alveolar oxygen gradient (mean difference -4.36 mmHg, 95% CI -7.19- -1.52 mmHg, p=0.003) all significantly improved in GM-CSF-treated patients with minor statistical heterogeneity (I=0%). No serious trial-related adverse events were reported.
CONCLUSIONS
Patients with aPAP treated with inhaled GM-CSF demonstrated significant improvements in symptoms, dyspnoea scores, lung function, gas exchange and radiology indices after treatment with nebulised GM-CSF of varying duration. There is an important need to review comparative effectiveness and patient choice in key clinical outcomes between the current standard of care, whole lung lavage, with the noninvasive treatment of nebulised GM-CSF in aPAP.
Topics: Humans; Pulmonary Alveolar Proteinosis; Granulocyte-Macrophage Colony-Stimulating Factor; Administration, Inhalation; Oxygen
PubMed: 37993127
DOI: 10.1183/16000617.0080-2023 -
GeroScience Apr 2024In the context of a globally aging population, exploring interventions that counteract age-related cognitive decline and cerebral structural alterations is paramount.... (Meta-Analysis)
Meta-Analysis
In the context of a globally aging population, exploring interventions that counteract age-related cognitive decline and cerebral structural alterations is paramount. Among various strategies, physical exercise (PE) emerges as a prevalent activity routinely incorporated in many individuals' lives. This systematic review and meta-analysis aims to elucidate the impact of PE on white matter (WM) integrity and cognitive function in older adults. Data from 581 participants, 312 in the PE intervention group, and 269 in the control group were extracted from nine randomized controlled trials (RCTs) retrieved from databases including PubMed, Embase, Web of Science, and the Cochrane Library. The results indicated a significant improvement in white matter (WM) integrity in individuals engaged in PE, as evidenced by enhanced fractional anisotropy (FA) scores (SMD = 0.4, 95% confidence interval (CI) [0.05, 0.75], P = 0.024). The GRADE assessment revealed a moderate risk. However, no significant associations were found between PE and other metrics such as radial diffusivity (RD), mean diffusivity (MD), white matter volume (WMV), hippocampal volume (HV), and cognitive functions (executive function [EF], memory, processing speed). In conclusion, our study emphasizes the potential neurostructural and cognitive functional benefits of physical exercise for the brain health of older adults.
Topics: Humans; Aged; White Matter; Diffusion Tensor Imaging; Cognition; Brain; Exercise
PubMed: 38108993
DOI: 10.1007/s11357-023-01033-8 -
Neurosurgical Review Jul 2023The dentato-rubro-olivary pathway, also known as the Guillain-Mollaret triangle (GMT) or myoclonic triangle, consists of the dentate nucleus, the red nucleus, and the... (Review)
Review
The dentato-rubro-olivary pathway, also known as the Guillain-Mollaret triangle (GMT) or myoclonic triangle, consists of the dentate nucleus, the red nucleus, and the inferior olivary nucleus (ION). GMT is important for motor coordination and control, and abnormalities in this network can lead to various neurological disorders. The present study followed a systematic approach in conducting a review on GMT studies. The inclusion criteria were limited to human subjects with primary objectives of characterizing and evaluating GMT syndromes, and the methodology used was not a determining factor for eligibility. The search strategy used MeSH terms and keywords relevant to the study's objective in various databases until August 2022. A total of 76 studies were included in the review after assessing 527 articles for eligibility based on the final inclusion criteria. Most of the studies evaluated the GMT in human subjects, with the majority utilizing magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), or combination of them. The review found that Hypertrophic olivary degeneration (HOD), a common consequence of GMT damage, has diverse underlying causes, including stroke, brainstem cavernous malformations, and structural impairments. Palatal tremor, ocular myoclonus, ataxia, nystagmus, and vertigo were frequently reported symptoms associated with HOD. This systematic review provides comprehensive insights into the association between GMT and various neurological syndromes, shedding light on the diagnostic, etiological, and prognostic aspects of GMT dysfunction. Understanding the role of the GMT and its implications in movement disorders could pave the way for improved treatment options and better management of neurological conditions related to this critical brainstem pathway.
Topics: Humans; Diffusion Tensor Imaging; Syndrome; Olivary Nucleus; Magnetic Resonance Imaging; Stroke; Hypertrophy
PubMed: 37468768
DOI: 10.1007/s10143-023-02086-1 -
Epilepsia Aug 2023Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a popular minimally invasive alternative to open resective surgery for... (Meta-Analysis)
Meta-Analysis Review
Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a popular minimally invasive alternative to open resective surgery for drug-resistant epilepsy (DRE). We sought to perform a systematic review and individual participant data meta-analysis to identify independent predictors of seizure outcome and complications following MRgLITT for DRE. Eleven databases were searched from January 1, 2010 to February 6, 2021 using the terms "MR-guided ablation therapy" and "epilepsy". Multivariable mixed-effects Cox and logistic regression identified predictors of time to seizure recurrence, seizure freedom, operative complications, and postoperative neurological deficits. From 8705 citations, 46 studies reporting on 450 MRgLITT DRE patients (mean age = 29.5 ± 18.1 years, 49.6% female) were included. Median postoperative seizure freedom and follow-up duration were 15.5 and 19.0 months, respectively. Overall, 240 (57.8%) of 415 patients (excluding palliative corpus callosotomy) were seizure-free at last follow-up. Generalized seizure semiology (hazard ratio [HR] = 1.78, p = .020) and nonlesional magnetic resonance imaging (MRI) findings (HR = 1.50, p = .032) independently predicted shorter time to seizure recurrence. Cerebral cavernous malformation (CCM; odds ratio [OR] = 7.97, p < .001) and mesial temporal sclerosis/atrophy (MTS/A; OR = 2.21, p = .011) were independently associated with greater odds of seizure freedom at last follow-up. Operative complications occurred in 28 (8.5%) of 330 patients and were independently associated with extratemporal ablations (OR = 5.40, p = .012) and nonlesional MRI studies (OR = 3.25, p = .017). Postoperative neurological deficits were observed in 53 (15.1%) of 352 patients and were independently predicted by hypothalamic hamartoma etiology (OR = 5.93, p = .006) and invasive electroencephalographic monitoring (OR = 4.83, p = .003). Overall, MRgLITT is particularly effective in treating patients with well-circumscribed lesional DRE, such as CCM and MTS/A, but less effective in nonlesional cases or lesional cases with a more diffuse epileptogenic network associated with generalized seizures. This study identifies independent predictors of seizure freedom and complications following MRgLITT that may help further guide patient selection.
Topics: Humans; Female; Child; Adolescent; Young Adult; Adult; Middle Aged; Male; Treatment Outcome; Laser Therapy; Magnetic Resonance Imaging; Drug Resistant Epilepsy; Seizures; Magnetic Resonance Spectroscopy; Lasers; Retrospective Studies
PubMed: 36824029
DOI: 10.1111/epi.17560 -
Drug Safety Apr 2024Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus (HIV) epidemic, people living with HIV have represented most cases for more than a decade. With the diffusion of highly active antiretroviral therapy, this group progressively decreased in favor of patients undergoing treatment with targeted therapy/immunomodulators. In this systematic review and meta-analysis, the objective was to assess which drugs are most frequently related to PML development, and report the incidence of drug-induced PML through a meta-analytic approach.
METHODS
The electronic databases MEDLINE, EMBASE, ClinicalTrials.gov, Web of Science and the Canadian Agency for Drugs and Technologies in Health Database (CADTH) were searched up to May 10, 2022. Articles that reported the risk of PML development after treatment with immunomodulatory drugs, including patients of both sexes under the age of 80 years, affected by any pathology except HIV, primary immunodeficiencies or malignancies, were included in the review. The incidence of drug-induced PML was calculated based on PML cases and total number of patients observed per 100 persons and the observation time. Random-effect metanalyses were conducted for each drug reporting pooled incidence with 95% confidence intervals (CI) and median (interquartile range [IQR]) of the observation time. Heterogeneity was measured by I statistics. Publication bias was examined through funnel plots and Egger's test.
RESULTS
A total of 103 studies were included in the systematic review. In our analysis, we found no includible study reporting cases of PML during the course of treatment with ocrelizumab, vedolizumab, abrilumab, ontamalimab, teriflunomide, daclizumab, inebilizumab, basiliximab, tacrolimus, belimumab, infliximab, firategrast, disulone, azathioprine or danazole. Dalfampridine, glatiramer acetate, dimethyl fumarate and fingolimod show a relatively safe profile, although some cases of PML have been reported. The meta-analysis showed an incidence of PML cases among patients undergoing rituximab treatment for multiple sclerosis (MS) of 0.01 cases/100 persons (95% CI - 0.08 to 0.09; I = 20.4%; p = 0.25) for a median observation period of 23.5 months (IQR 22.1-42.1). Treatment of MS with natalizumab carried a PML risk of 0.33 cases/100 persons (95% CI 0.29-0.37; I = 50%; p = 0.003) for a median observation period of 44.1 months (IQR 28.4-60) and a mean number of doses of 36.3 (standard deviation [SD] ± 20.7). When comparing data about patients treated with standard interval dosing (SID) and extended interval dosing (EID), the latter appears to carry a smaller risk of PML, that is, 0.08 cases/100 persons (95% CI 0.0-0.15) for EID versus 0.3 cases/100 persons (95% CI 0.25-0.34) for SID.
CONCLUSIONS
A higher risk of drug-related PML in patients whose immune system is not additionally depressed by means of neoplasms, HIV or concomitant medications is found in the neurological field. This risk is higher in MS treatment, and specifically during long-term natalizumab therapy. While this drug is still routinely prescribed in this field, considering the efficacy in reducing MS relapses, in other areas it could play a smaller role, and be gradually replaced by other safer and more recently approved agents.
Topics: Male; Female; Humans; Aged, 80 and over; Natalizumab; Leukoencephalopathy, Progressive Multifocal; Canada; Immunologic Factors; Multiple Sclerosis; HIV Infections
PubMed: 38321317
DOI: 10.1007/s40264-023-01383-4 -
Global Spine Journal Jun 2024Systematic review.
STUDY DESIGN
Systematic review.
OBJECTIVE
Degenerative cervical myelopathy (DCM) is a common spinal cord disorder necessitating surgery. We aim to explore how effectively diffusion tensor imaging (DTI) can distinguish DCM from healthy individuals and assess the relationship between DTI metrics and symptom severity.
METHODS
We included studies with adult DCM patients who had not undergone decompressive surgery and implemented correlation analyses between DTI parameters and severity, or compared healthy controls and DCM patients.
RESULTS
57 studies were included in our meta-analysis. At the maximal compression (MC) level, fractional anisotropy (FA) exhibited lower values in DCM patients, while apparent diffusion coefficient (ADC), mean diffusivity (MD), and radial diffusivity (RD) were notably higher in the DCM group. Moreover, our investigation into the diagnostic utility of DTI parameters disclosed high sensitivity, specificity, and area under the curve values for FA (.84, .80, .83 respectively) and ADC (.74, .84, .88 respectively). Additionally, we explored the correlation between DTI parameters and myelopathy severity, revealing a significant correlation of FA (.53, 95% CI:0.40 to .65) at MC level with JOA/mJOA scores.
CONCLUSION
Current guidelines for DCM suggest decompressive surgery for both mild and severe cases. However, they lack clear recommendations on which mild DCM patients might benefit from conservative treatment vs immediate surgery. ADC's role here could be pivotal, potentially differentiating between healthy individuals and DCM. While it may not correlate with symptom severity, it might predict surgical outcomes, making it a valuable imaging biomarker for clearer management decisions in mild DCM.
PubMed: 38877604
DOI: 10.1177/21925682241263792 -
Respiratory Research Mar 2024The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the... (Review)
Review
BACKGROUND
The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR).
METHODS
PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported.
RESULTS
We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns.
CONCLUSIONS
The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.
Topics: Humans; Female; Adult; Middle Aged; Male; Lung Diseases, Interstitial; Lung; Scleroderma, Systemic; Biopsy; Prognosis
PubMed: 38521926
DOI: 10.1186/s12931-024-02725-1 -
European Journal of Haematology Dec 2023The treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) changed remarkably since the European Medicines Agency-approved chimeric antigen...
Cost-effectiveness analysis of transplant-ineligible relapsed or refractory diffuse large B-cell lymphoma treatment options-Experience of the efficiency frontier approach.
OBJECTIVES
The treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) changed remarkably since the European Medicines Agency-approved chimeric antigen receptor T-cell (CAR-T) therapies (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tisagenlecleucel [tisa-cel]) for the third-line onwards (3+L), and targeted therapies (polatuzumab vedotin-bendamustine-rituximab [pola-BR], tafasitamab-lenalidomide [Tafa-L]) for the second-line (2L) onwards. As associated rising treatment costs represent an economic burden, the cost-effectiveness of transplant-ineligible R/R DLBCL interventions was assessed from a German healthcare payer's perspective, using the efficiency frontier (EF) approach.
METHODS
A systematic literature review was performed to determine the clinical benefit concerning median overall survival (OS) of bendamustine-rituximab (BR), rituximab-gemcitabine-oxaliplatin (R-GemOx), axi-cel, liso-cel, tisa-cel, pola-BR, and Tafa-L. First-year treatment costs (drug and medical services costs) were calculated. Results were merged on two-dimensional graphs illustrating 2L and 3+L EFs.
RESULTS
Second-line EF is formed by BR (median OS 11.49 months, €23 958) and Tafa-L (45.7, €104 541), 3+L EF is formed by R-GemOx (12.0, €29 080), Tafa-L (15.5, €104 541), and axi-cel (18.69, €308 516). These interventions build the respective cost-effectiveness thresholds for novel interventions.
CONCLUSIONS
Using the EF approach, the currently most cost-effective interventions (based on cost-effectiveness ratios) in the indication of R/R DLBCL were identified to guide international reimbursement decisions.
Topics: Humans; Cost-Effectiveness Analysis; Bendamustine Hydrochloride; Rituximab; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Immunotherapy, Adoptive; Antigens, CD19
PubMed: 37644352
DOI: 10.1111/ejh.14095 -
Brain Imaging and Behavior Dec 2023The microstructural characteristics of white and gray matter in mild cognitive impairment (MCI) and the early-stage of Alzheimer's disease (AD) remain unclear. This... (Meta-Analysis)
Meta-Analysis Review
The microstructural characteristics of white and gray matter in mild cognitive impairment (MCI) and the early-stage of Alzheimer's disease (AD) remain unclear. This study aimed to systematically identify the microstructural damages of MCI/AD in studies using neurite orientation dispersion and density imaging (NODDI), and explore their correlations with cognitive performance. Multiple databases were searched for eligible studies. The 10 eligible NODDI studies were finally included. Patients with MCI/AD showed overall significant reductions in neurite density index (NDI) of specific white matter structures in bilateral hemispheres (left hemisphere: -0.40 [-0.53, -0.27], P < 0.001; right: -0.33 [-0.47, -0.19], P < 0.001), involving the bilateral superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), the left posterior thalamic radiation (PTR), and the left cingulum. White matter regions exhibited significant increased orientation dispersion index (ODI) (left: 0.25 [0.02, 0.48], P < 0.05; right: 0.27 [0.07, 0.46], P < 0.05), including the left cingulum, the right UF, and the bilateral parahippocampal cingulum (PHC), and PTR. Additionally, the ODI of gray matter showed significant reduction in bilateral hippocampi (left: -0.97 [-1.42, -0.51], P < 0.001; right: -0.90 [-1.35, -0.45], P < 0.001). The cognitive performance in MCI/AD was significantly associated with NDI (r = 0.50, P < 0.001). Our findings highlight the microstructural changes in MCI/AD were characterized by decreased fiber orientation dispersion in the hippocampus, and decreased neurite density and increased fiber orientation dispersion in specific white matter tracts, including the cingulum, UF, and PTR. Moreover, the decreased NDI may indicate the declined cognitive level of MCI/AD patients.
Topics: Humans; Brain; Gray Matter; Alzheimer Disease; Diffusion Tensor Imaging; Magnetic Resonance Imaging; White Matter; Cognitive Dysfunction
PubMed: 37752311
DOI: 10.1007/s11682-023-00805-2