Retinal and choroidal changes after anti-VEGF therapy in neovascular-AMD patients: A systematic review and meta-analysis of SD-OCT studies.

BACKGROUND: In recent years, the progress made in the field of optical coherence tomography has helped to understand the changes in eye layers in patients with exudative age-related macular degeneration (nAMD). Early diagnosis of nAMD, a leading cause of irreversible vision impairment, is helpful. Therefore, we performed a meta-analysis on OCT measurement alterations before and after anti-VEGF therapy in patients with nAMD and controls. METHOD: We systematically searched Scopus, PubMed, Cochrane, and Web of Science to find articles that measured choroidal and retinal layer changes after anti-VEGF therapy in nAMD Patients. We chose either a fixed-effects or random-effects model based on the assessed heterogeneity level to perform a meta-analysis. In addition, we conducted meta-regression, subgroup analyses, publication bias, and quality assessment for included studies. RESULTS: Thirteen studies were included in the meta-analysis, with 733 total participants. Foveal thickness and subfoveal choroidal thickness (CT) decreased significantly in the first 3 years after injections, except for subfoveal CT in the third year after injection. It also showed that CT at 1500 µm temporal and nasal to the fovea did not significantly change. CONCLUSION: Our results showed anti-VEGF treatment for nAMD patients was associated with a significant reduction in foveal thickness and subfoveal CT in the first 2 years after treatment. Our analysis did not reveal any correlation between changes in foveal thickness and subfoveal CT with best-corrected visual acuity or other factors.

Hypermobile lateral meniscus: A systematic review of current treatment options.

PURPOSE: The reliable data on the incidence of hypermobile lateral meniscus (HLM) and its clinical manifestations, diagnostic methods and therapeutic approaches are limited. This systematic study aimed to review available treatment options for HLM and the outcomes of each approach. METHODS: A systematic search was performed in four electronic databases (PubMed, EMBASE, Scopus, Web of Science) to identify studies in which arthroscopically confirmed cases of HLM were treated surgically or nonsurgically, and the required data comprising study characteristics, patient data, treatment approaches and outcome measures were extracted from eligible studies. RESULTS: Twenty studies with a total of 212 patients (138 males and 74 females) and 219 knees were included. The most frequently reported symptoms were locking sensations, knee pain, giving way and snapping. Treatments used by the studies were: radiofrequency energy in two studies; arthroscopic partial meniscectomy in one study; open surgery in two studies; and arthroscopic meniscal repair in 17 studies. Eleven studies used an all-inside repair method and an inside-out meniscal repair was reported in eight studies. Three studies reported the usage of posterior arthroscopy for therapeutic or diagnostic approaches. Evaluation of symptom resolution was the main outcome measurement for which almost all of the studies stated relief of symptoms after intervention. CONCLUSION: Despite the lack of definite consensus about the most appropriate intervention for HLM, therapeutic preference was directed towards arthroscopic all-inside and inside-out repair techniques. Although the surgeon's decision remains the key factor in choosing the most suitable treatment option for each individual, posterior arthroscopic meniscal repair may be considered as a better option for HLM treatment according to the findings of this review. LEVEL OF EVIDENCE: Level IV.

Artificial intelligence in osteoarthritis detection: A systematic review and meta-analysis.

OBJECTIVES: As an increasing number of studies apply artificial intelligence (AI) algorithms in osteoarthritis (OA) detection, we performed a systematic review and meta-analysis to pool the data on diagnostic performance metrics of AI, and to compare them with clinicians' performance. MATERIALS AND METHODS: A search in PubMed and Scopus was performed to find studies published up to April 2022 that evaluated and/or validated an AI algorithm for the detection or classification of OA. We performed a meta-analysis to pool the data on the metrics of diagnostic performance. Subgroup analysis based on the involved joint and meta-regression based on multiple parameters were performed to find potential sources of heterogeneity. The risk of bias was assessed using Prediction Model Study Risk of Bias Assessment Tool reporting guidelines. RESULTS: Of the 61 studies included, 27 studies with 91 contingency tables provided sufficient data to enter the meta-analysis. The pooled sensitivities for AI algorithms and clinicians on internal validation test sets were 88% (95% confidence interval [CI]: 86,91) and 80% (95% CI: 68,88) and pooled specificities were 81% (95% CI: 75,85) and 79% (95% CI: 80,85), respectively. At external validation, the pooled sensitivity and specificity for AI algorithms were 94% (95% CI: 90,97) and 91% (95% CI: 77,97), respectively. CONCLUSION: Although the results of this meta-analysis should be interpreted with caution due to the potential pitfalls in the included studies, the promising role of AI as a diagnostic adjunct to radiologists is indisputable.

Optical coherence tomography angiography measurements in Parkinson's disease: A systematic review and meta-analysis.

Optical coherence tomography angiography (OCT-A) is an ocular imaging technology that has emerged as a non-invasive tool to evaluate retinal microvascular changes in neurodegenerative diseases including Parkinson's disease (PD) and Alzheimer's disease. While several studies have reported on the presence of pathologic retinal microvascular alterations in PD, the utility of OCT-A as a biomarker for PD evaluation is still unclear. A systematic review and meta-analysis were performed to explore the current evidence for the role of OCT-A in PD published up until June 2022. PubMed, Scopus, and Web of Science databases were used to systematically identify relevant papers and a meta-analysis was conducted using Stata16 software according to the level of heterogeneity applying a random- or fixed-effect model. Thirteen studies of 925 eyes in the PD group and 1501 eyes in the control group assessing OCT-A findings in PD patients were included. The meta-analyses revealed that the foveal region of PD patients had a significantly lower vessel density in the superficial capillary plexus (SCP) compared to healthy controls but that there were no significant differences in the foveal avascular zone, the SCP in whole, parafoveal, and perifoveal regions, and deep capillary plexus. OCT-A metrics may act as a potential biomarker for a more accurate and early PD diagnosis. Still, the OCT-A algorithms and interchangeability between OCT-A devices require further standardization to draw clinical conclusions regarding their utility.

Optical coherence tomography angiography measurements in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography-angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue. METHODS: PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level. RESULTS: The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P < 0.0001). CONCLUSIONS: This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities.

Choroidal thickness in eyes of migraine patients measured using spectral domain-optical coherence tomography: A meta-analysis.

Recent developments in high-resolution optical coherence tomography allow evaluation of even the slightest changes of choroidal thickness in various disorders, including migraine. In this review, we analyze the choroidal thickness measurements reported in various studies that compare results between migraineurs and healthy individuals. We searched PubMed, Scopus, and EMBASE to identify relevant literature reporting choroidal thickness in the migraineurs' different macular regions compared with healthy controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level. Moreover, subgroup analyses, meta-regression, publication bias, and quality assessment were also performed. We identified ten studies involving 580 migraineurs (173 with aura, 128 without aura, and 279 without specification for the presence of aura) and 407 healthy controls to be included in this meta-analysis. Results indicated that average choroidal thickness was significantly decreased in the migraine cases (SMD, -1.28; 95% CI, -2.47 to -0.08; P = 0.04) compared to healthy individuals. Furthermore, both with aura (SMD, -1.16; 95% CI, -1.39 to -0.92; P < 0.0001) and without aura migraine patients (SMD, -0.81; 95% CI, -1.28 to -0.34; P < 0.001) had significantly thinner subfoveal choroid compared to healthy controls. Moreover, subfoveal choroidal thickness in the migraineurs with aura was significantly lower than those without aura (SMD, -0.45; 95% CI, -0.84 to -0.05; P = 0.03). The alterations in choroidal thickness, suggestive of migraine's neurovascular pathophysiology, were tentatively confirmed by this study's findings. Further longitudinal studies with more diverse settings are required to derive more definitive conclusions.

Olfactory system measurements in COVID-19: a systematic review and meta-analysis.

PURPOSE: The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls. METHODS: PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted. RESULTS: Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators. CONCLUSION: The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.

Retinal and choroidal changes in AMD: A systematic review and meta-analysis of spectral-domain optical coherence tomography studies.

Optical coherence tomography is a noninvasive imaging technology using the optical reflectivity of tissues that is capable of detecting quantitative and qualitative biomarkers of age-related macular degeneration (AMD) that cannot be similarly recognized in conventional imaging. We systematically searched PubMed and Embase databases to identify relevant articles to this subject. A fixed-effect or random-effect model was applied for the meta-analysis based on the heterogeneity level. In addition, subgroup analyses, meta-regression, publication bias, and quality assessment were also performed. Twenty-five studies with 1,632 cases and 1,445 healthy controls in total were included. Our results revealed that, when compared to controls, AMD subjects showed a significantly lower thickness in the choroid at 500 µm temporal, 1,500 µm nasal, and temporal to the fovea, subfoveal choroid, average peripapillary retinal nerve fiber layer, and average macular ganglion cell complex (GCC); however, average and central choroidal thickness 500 µm nasal, 1,000 µm nasal and temporal to the fovea, central and parafoveal macular GCC, retinal nerve fiber layer, and inner plexiform layer, and central macular thickness did not change significantly. Various regional analyses showed several other significant differences. The findings of the current study confirm that some retinal layers are altered in AMD patients compared to healthy controls. Thus, future studies are required to derive more definitive conclusions.

Brain microstructural alterations of depression in Parkinson's disease: A systematic review of diffusion tensor imaging studies.

Depression, a leading cause of disability worldwide, is also the most prevalent psychiatric problem among Parkinson disease patients. Both depression and Parkinson disease are associated with microstructural anomalies in the brain. Diffusion tensor imaging techniques have been developed to characterize the abnormalities in cerebral tissue. We included 11 studies investigating brain microstructural abnormalities in depressed Parkinson's disease patients. The included studies found alterations to essential brain structural networks, including impaired network integrity for specific cortical regions, such as the temporal and frontal cortices. Additionally, findings indicate that microstructural changes in specific limbic structures, such as the prefronto-temporal regions and connecting white matter pathways, are altered in depressed Parkinson's disease compared to non-depressed Parkinson's disease and healthy controls. There remain inconsistencies between studies reporting DTI measures and depression severity in Parkinson disease participants. Additional research evaluating underlying neurobiological relationships between major depression, depressed Parkinson's disease, and non-depressed Parkinson's disease is required to disentangle further mechanisms that underlie depression and related somatic symptoms, in Parkinson disease.

Comparison of spermatic and peripheral blood gases and their correlation with spermogram pattern and varicocele grade in patients with a varicocele.

The relationship between infertility and varicocele is still a controversial topic. This study aimed to find the association between the venous blood gas (VBG) pattern of the spermatic veins and peripheral veins with varicocele grade and spermogram variables in infertile patients. A total of 47 patients with a varicocele were enrolled in this study. Blood samples were drawn simultaneously from the spermatic vein and a peripheral vein. The pH, partial pressure of oxygen, the partial pressure of carbon dioxide, oxygen saturation, and bicarbonate values of these samples were analysed. The mean age of participants was 30.48 ± 6.08. The mean volume of semen was 3.92 ± 1.57 mL, and the mean semen pH was 7.88 ± 0.22. The pH was higher (p < 0.01) in the spermatic vein compared with the peripheral vein. However, level of other parameters including pO2 (p = 0.662), pCO2 (p < 0.001), HCO3 concentration of serum (p < 0.01), and base excess (p = 0.172) were lower in the spermatic vein in comparison with the peripheral vein. Correlations between VBGs determinants of the varicocele patients' spermatic vein and sperm morphology and motility were insignificant. In conclusion, although the clinical significance of VBGs is evident, there are limited studies that investigated the VBGs in varicocele patients. We should consider that the deviation in blood gases may be the missing piece in the puzzle to understand the pathophysiology of varicocele. By knowing the pathophysiology more precisely, we can better decide the ideal treatment option for the patients.

Associations of refractive errors and retinal changes measured by optical coherence tomography: A systematic review and meta-analysis.

Studies reporting alteration in retinal thickness using optical coherence tomography (OCT) have been performed in different populations with various degrees of refractive error, producing inconsistent results. Therefore, we performed a meta-analysis to evaluate the alterations in retinal OCT measurements in myopic and hyperopic patients compared to controls. Evaluation of different retinal layers' thickness may have significance for developing novel approaches for preventing, diagnosing, and treating refractive errors and their complications. We searched PubMed and EMBASE to identify articles that reported OCT measurements of different retinal layers and regions, including macular, foveal, parafoveal, perifoveal, foveolar, ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell and inner plexiform layer (GC-IPL) thickness in addition to macular volume, and optic disc area in myopes and hyperopes comparing their differences with controls. We applied either a fixed-effects or random-effects model for the meta-analysis of these differences based on the assessed heterogeneity level. Furthermore, subgroup analyses and metaregression, as well as publication bias and quality assessment, were conducted for the eligible studies. Forty-seven studies with a total of 12223 eyes, including 8600 cases and 3623 non-cases, are included in this meta-analysis. Our results showed that, in comparison to controls, highly myopic eyes had a significantly lower value for mean macular thickness, macular GCC, macular GC-IPL, parafoveal, perifoveal, foveal, foveolar, RNFL, and pRNFL thickness. Compared to controls, moderately myopic eyes showed a significantly thinner mean macular GCC layer and pRNFL. On the other hand, hyperopic eyes had significantly thicker average pRNFL than controls. Several other significant differences were also observed in various regional analyses. The findings of the current study affirm the retinal OCT measurement differences between myopic and hyperopic eyes compared to controls, emphasizing OCT measurements' advantages as potential biomarkers of ocular pathologies.

Interferon therapy in patients with SARS, MERS, and COVID-19: A systematic review and meta-analysis of clinical studies.

Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR = -0.05, 95% CI: (-0.71,0.62), I2 = 44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR = -0.44, 95% CI: (-1.13,0.25), I2 = 31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.

Enterocutaneous fistula formation thirty years after a femoral neck fracture fixation with lag screws: A case report.

INTRODUCTION AND IMPORTANCE: As the population grows older, femoral neck fracture is becoming one of the prevalent cases in orthopedics, although this fracture can also happen in younger individuals following high energy traumas. Fixation with cancellous lag screws is one treatment option for femoral neck fractures, especially for young adults and relatively active older patients. CASE PRESENTATION: In this case report, we describe a 52-year-old man referred with the formation of enterocutaneous fistula (ECF) in the surgery place for fixation of a femoral neck fracture 30 years prior to presentation. CLINICAL DISCUSSION: Interpretation of CT scan images as well as findings of the performed laparotomy suggested that fixation procedure with screws was probably the main culprit for penetration of ileum. Subsequently, the removal of screws enabled the fistula to reach the surface of skin, which presented with fecal drainage. To eliminate fistula, we performed right hemicolectomy and ileocolic anastomosis for the case. CONCLUSION: Since management of ECF remains among the most challenging problems for surgeons, this unique case report indicates the possibility for formation of such fistula following a fixation procedure in the hip joint area, even after thirty years and stresses on taking measures in order to prevent fistula formation caused by the prevalent procedures performed on the hip joint.

Cytokine release syndrome: inhibition of pro-inflammatory cytokines as a solution for reducing COVID-19 mortality.

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.

The NLRP3 inflammasome: a therapeutic target for inflammation-associated cancers.

Introduction: Inflammasomes are large multimeric intracellular complexes that are capable of maturation and secretion of pro-inflammatory cytokines, IL-1ß and IL-18, in response to danger signal molecules. As a member of the inflammasome family, the NLRP3 inflammasome has recently been under intense investigation revealing its possible role in several human diseases especially cancers.Areas covered: In this review, we will discuss the biology and mechanism of NLRP3 inflammasome activation, its role in specific types of tumors and the novel therapeutic modalities targeting this complex.Expert opinion: The NLRP3 inflammasome and its components including the adapter apoptosis-associated speck-like (ASC) protein and caspase-1 impose different and sometimes contrasting effects in tumorigenesis depending on various contexts. Considering the novel role of this complex in the initiation and progression of neoplasia, the NLRP3 inflammasome and its pathways provide desirable therapeutic targets for prevention, treatment, and prognosis of certain types of cancer. To date, several agents have been introduced for this purpose, some of which have shown promising results in the clinic.