Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia.

OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.

Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

[Figure: see text].

Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis.

OBJECTIVES: Acute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk. We performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19. METHODS: Relevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, IL-1, coronavirus, COVID-19, SARS-CoV-2. Trials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19 were included. RESULTS: Nine studies (n = 1119) were eligible for inclusion in the present meta-analysis. Their bias risk with reference to the assessed parameters was high. In pooled analyses, anakinra reduced the need for invasive mechanical ventilation (odds ratio (OR): 0.38, 95% CI: 0.17-0.85, P = 0.02, I2 = 67%; six studies, n = 587) and mortality risk (OR: 0.32, 95% CI: 0.23-0.45, P < 0.00001, I2 = 0%; nine studies, n = 1119) compared with standard of care therapy. There were no differences regarding the risk of adverse events, including liver dysfunction (OR: 0.75, 95% CI: 0.48-1.16, P > 0.05, I2 = 28%; five studies, n = 591) and bacteraemia (OR: 1.07, 95% CI: 0.42-2.73, P > 0.05, I2 = 71%; six studies, n = 727). CONCLUSIONS: Available evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events. Confirmation of efficacy and safety requires randomized placebo-controlled trials.

Implantable Cardiac Monitoring in the Secondary Prevention of Cryptogenic Stroke.

OBJECTIVE: In this study, we sought to evaluate the impact of implantable cardiac monitoring (ICM) in the prevention of stroke recurrence after a cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We evaluated consecutive patients with cryptogenic ischemic stroke or TIA admitted in a comprehensive stroke center during an 8-year period. We compared the baseline characteristics and outcomes between patients receiving conventional cardiac monitoring with repeated 24-hour Holter-monitoring during the first 5 years in the outpatient setting and those receiving continuous cardiac monitoring with ICM during the last 3 years. Associations on the outcomes of interest were further assessed in multivariable regression models adjusting for potential confounders. RESULTS: We identified a total of 373 patients receiving conventional cardiac monitoring and 123 patients receiving ICM. Paroxysmal atrial fibrillation (PAF) detection was higher in the ICM cohort compared to the conventional cardiac monitoring cohort (21.1% vs 7.5%, p < 0.001). ICM was independently associated with an increased likelihood of PAF detection during follow-up (hazard ratio [HR] = 1.94, 95% confidence interval [CI] = 1.16-3.24) in multivariable analyses. Patients receiving ICM were also found to have significantly higher rates of anticoagulation initiation (18.7% vs 6.4%, p < 0.001) and lower risk of stroke recurrence (4.1% vs 11.8%, p = 0.013). ICM was independently associated with a lower risk of stroke recurrence during follow-up (HR = 0.32, 95% CI = 0.11-0.90) in multivariable analyses. INTERPRETATION: ICM appears to be independently associated with a higher likelihood of PAF detection and anticoagulation initiation after a cryptogenic ischemic stroke or TIA. ICM was also independently related to lower risk of stroke recurrence in our cryptogenic stroke / TIA cohort. ANN NEUROL 2020;88:946-955.

Greater decline of acute stroke admissions compared with acute coronary syndromes during COVID-19 outbreak in Greece: Cerebro/cardiovascular implications amidst a second wave surge.

BACKGROUND AND PURPOSE: A remarkable decline in admissions for acute stroke and acute coronary syndrome (ACS) has been reported in countries severely hit by the COVID-19 pandemic. However, limited data are available from countries with less COVID-19 burden focusing on concurrent stroke and ACS hospitalisation rates from the same population. METHODS: The study was conducted in three geographically and demographically representative COVID-19 referral university hospitals in Greece. We recorded the rate of stroke and ACS hospital admissions during a 6-week period of the COVID-19 outbreak in 2020 and compared them with the rates of the corresponding period in 2019. RESULTS: We found a greater relative reduction of stroke admissions (51% [35 vs. 71]; incidence rate ratio [IRR]: 0.49, p = 0.001) compared with ACS admissions (27% [123 vs. 168]; IRR: 0.73, p = 0.009) during the COVID-19 outbreak (p = 0.097). Fewer older (>65 years) patients (stroke: 34.3% vs. 45.1%, odds ratio [OR]: 0.64, p = 0.291; ACS: 39.8% vs. 54.2%, OR: 0.56, p = 0.016) were admitted during the COVID-19 compared with the control period. CONCLUSIONS: Hospitalisation rates both for stroke and ACS were reduced during the COVID-19 outbreak in a country with strict social distancing measures, low COVID-19 incidence and low population mortality. Lack of triggers for stroke and ACS during social distancing/quarantining may explain these observations. However, medical care avoidance attitudes among cerebro/cardiovascular patients should be dissipated amidst the rising second COVID-19 wave.

Trichinosis Imitating an Inflammatory Systematic Disease.

Trichinellosis (trichinosis) is a parasitic infection caused by nematodes of the genus Trichinella. Pigs are the most common source of human infection. We describe a case of a 47-year-old woman presented with a wide range of intermittent symptoms including prolonged fever, dry cough, diarrhea, rash, myalgias and arthralgias. The patient was attended by physicians with various medical specialties such as dermatologists, rheumatologists and allergiologists, but they did not establish a certain diagnosis because of the gradual onset of symptoms, raising the suspicion of a systematic disease. After extensive work up, the diagnosis of trichinosis was established with femoral muscle biopsy compatible with inflammatory myopathy of parasitic etiology with trichinosis to be the predominant diagnosis. Despite the significant delay of diagnosis for almost three months, patient was treated successfully with no further complications. Trichinellosis is a food-borne treatable infection. Preventive measures include community education especially in zones where parasite prevalence is increased, improvement of farming and cooking techniques.

Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study.

BACKGROUND: Hepatobiliary and pancreatic manifestations have been reported in patients with Crohn's disease or ulcerative colitis. Our aim was to describe the prevalence of hepatobiliary and pancreatic manifestations in inflammatory bowel disease and their association with the disease itself and the medications used. METHODS: Data were retrospectively extracted from the clinical records of patients followed up at our tertiary IBD referral Center. RESULTS: Our study included 602 IBD patients, with liver function tests at regular intervals. The mean follow-up was 5.8 years (Std. Dev.: 6.72). Abdominal imaging examinations were present in 220 patients and revealed findings from the liver, biliary tract and pancreas in 55% of examined patients (120/220). The most frequent findings or manifestations from the liver, biliary tract and pancreas were fatty liver (20%, 44/220), cholelithiasis (14.5%, 32/220) and acute pancreatitis (0.6%, 4/602), respectively. There were 7 patients with primary sclerosing cholangitis. Regarding hepatitis viruses, one-third of the patients had been tested for hepatitis B and C. 5% (12/225) of them had positive hepatitis B surface antigen and 13.4% had past infection with hepatitis B virus (positive anti-HBcore). In addition, most of the patients were not immune against hepatitis B (negative anti-HBs), while 3% of patients were anti-HCV positive and only one patient had active hepatitis C. Furthermore, 24 patients had drug-related side effects from the liver and pancreas. The side effects included 21 cases of hepatotoxicity and 3 cases of acute pancreatitis. Moreover, there were two cases of HBV reactivation and one case of chronic hepatitis C, which were successfully treated. CONCLUSION: In our study, approximately one out of four patients had some kind by a hepatobiliary or pancreatic manifestation. Therefore, it is essential to monitor liver function at regular intervals and differential diagnosis should range from benign diseases and various drug related side effects to severe disorders, such as primary sclerosing cholangitis.

The value of transesophageal echocardiography in the investigation and management of cryptogenic cerebral ischemia: a single-center experience.

The diagnostic utility of transesophageal echocardiography (TEE) has often been challenged in patients with cryptogenic stroke (CS). We estimated the prevalence of different findings on TEE examination of CS patients, their impact on secondary stroke prevention and the presence of potential age or gender disparities. We reviewed all TEE examinations that were performed in a single echocardiography laboratory during a 7-year-old period to identify CS patients that underwent investigation with TEE. Of the 518 total TEE examinations, we identified 88 CS patients. TEE revealed abnormal findings in 69.3 % of them. Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) were identified in 30.6 and 22.7 % of the patients. Ascending aorta and aortic arch atheromatosis was present in 26.1 % of the patients, with complex atheromatosis diagnosed in 14.7 % of them. Cardiac myxomas were uncovered in 2.3 %. Thrombi in the left atrium and in cardiac valves were reported in 3.4 and 2.3 % of the patients, respectively. Based on TEE findings, the therapeutic management would be very likely modified in 9.1 % of the patients. Subgroup analysis revealed no gender disparities on the prevalence of TEE findings and in secondary stroke prevention, while linear regression analyses revealed significant associations of age with the prevalence of PFO, ASA, aorta atheromatosis and complex aorta atheromatosis. TEE examination should be included in the diagnostic work-up of all CS patients, irrespective of age and gender status, since it can reveal potential sources of embolism and has a significant impact for secondary stroke prevention.

Levosimendan Improves Neurological Outcome in a Swine Model of Asphyxial Cardiac Arrest.

BACKGROUND: In asphyxial cardiac arrest, the severe hypoxic stress complicates the resuscitation efforts and results in poor neurological outcomes. Our aim was to assess the effects of levosimendan on a swine model of asphyxial cardiac arrest. METHODS: Asphyxial cardiac arrest was induced in 20 Landrace/Large White piglets, which were subsequently left untreated for four minutes. The animals were randomised to receive adrenaline alone (n=10, Group A) and adrenaline plus levosimendan (n=10, Group B). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Haemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first 30 minutes after return of spontaneous circulation (ROSC), while survival and neurologic alertness score were measured 24 hours later. RESULTS: Return of spontaneous circulation was achieved in six animals (60%) from Group A and nine animals (90%) from Group B (p=0.303). During the first minute of cardiopulmonary resuscitation, coronary perfusion pressure was significantly higher in Group B (p=0.046), but there was no significant difference at subsequent time points until ROSC. Although six animals (60%) from each group survived after 24 hours (p=1.000), neurologic examination was significantly better in the animals of Group B (p<0.01). CONCLUSIONS: The addition of levosimendan to adrenaline improved coronary perfusion pressure immediately after the onset of cardiopulmonary resuscitation and resulted in better 24-hour neurological outcome.

Complex atheromatous plaques in the descending aorta and the risk of stroke: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Proximal aortic plaques, especially in the aortic arch, have already been established as an important cause of stroke and peripheral embolism. However, aortic plaques situated in the descending thoracic aorta have recently been postulated as a potential embolic source in patients with cryptogenic cerebral infarction through retrograde aortic flow. The aim of the present study was to evaluate the potential association of descending aorta atheromatosis with cerebral ischemia. METHODS: We conducted a systematic review and meta-analysis of all available prospective observational studies reporting the prevalence of complex atheromatous plaques in the descending aorta in patients with stroke and in unselected populations undergoing examination with transesophageal echocardiography. RESULTS: We identified 11 eligible studies including a total of 4000 patients (667 patients with stroke and 3333 unselected individuals; mean age, 65 years; 55% men). On baseline transesophageal echocardiograpic examination, the prevalence of complex atheromatous plaques in the descending aorta was higher (P=0.001) in patients with stroke (25.4%; 95% confidence interval, 14.6-40.4%) compared with unselected individuals (6.1%; 95% confidence interval, 3.4-10%). However, no significant difference (P=0.059) in the prevalence of complex atheromatous plaques in the descending aorta was found between patients with cryptogenic (21.8%; 95% confidence interval, 17.5-26.9%) and unclassified (28.3%; 95% confidence interval, 23.9-33.1%) cerebral infarction. CONCLUSIONS: Our findings indicate that the presence of complex plaques in the descending aorta is presumably a marker of generalized atherosclerosis and high vascular risk. The present analyses do not provide any further evidence for a direct causal relationship between descending aorta atherosclerosis and cerebral embolism.

Brain involvement in patients with inflammatory bowel disease: a voxel-based morphometry and diffusion tensor imaging study.

OBJECTIVES: To investigate structural brain changes in inflammatory bowel disease (IBD). METHODS: Brain magnetic resonance imaging (MRI) was performed on 18 IBD patients (aged 45.16 ± 14.71 years) and 20 aged-matched control subjects. The imaging protocol consisted of a sagittal-FLAIR, a T1-weighted high-resolution three-dimensional spoiled gradient-echo sequence, and a multisession spin-echo echo-planar diffusion-weighted sequence. Differences between patients and controls in brain volume and diffusion indices were evaluated using the voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, respectively. The presence of white-matter hyperintensities (WMHIs) was evaluated on FLAIR images. RESULTS: VBM revealed decreased grey matter (GM) volume in patients in the fusiform and the inferior temporal gyrus bilaterally, the right precentral gyrus, the right supplementary motor area, the right middle frontal gyrus and the left superior parietal gyrus (p < 0.05). TBSS showed decreased axial diffusivity (AD) in the right corticospinal tract and the right superior longitudinal fasciculus in patients compared with controls. A larger number of WMHIs was observed in patients (p < 0.05). CONCLUSIONS: Patients with IBD show an increase in WMHIs and GM atrophy, probably related to cerebral vasculitis and ischaemia. Decreased AD in major white matter tracts could be a secondary phenomenon, representing Wallerian degeneration. KEY POINTS: • There is evidence of central nervous system involvement in IBD. • Diffusion tensor imaging detects microstructural brain abnormalities in IBD. • Voxel based morphometry reveals brain atrophy in IBD.

Racial disparities in early mortality in 1,134 young patients with acute stroke.

We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18-45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0-1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2-13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38-11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28-10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35-0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.

Atherosclerosis, biomarkers of atherosclerosis and Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent type of dementia, involving progressive deterioration of neuronal networks. Although the pathophysiological mechanism of AD is not fully elucidated, apart from ß-amyloid and tau protein, a diverse number of factors such as cardiovascular risk factors, inflammation, and lipids metabolism may play a significant role. Numerous epidemiological and laboratory studies support vascular injury and inflammation, as key pathological processes. The present review is focused on cardiovascular risk factors, lipids, and circulating biomarkers of inflammation, discussing them as independent mechanisms converging to the same final pathogenetic cascade of AD.

Waist Circumference and Body Mass Index as Predictors of Disability Progression in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: While obesity has been shown to elevate the risk of developing multiple sclerosis (MS), there is a lack of strong evidence regarding its role in the disability progression and status of MS patients. Methods: This systematic review and meta-analysis aimed to provide comparative estimates of WC and BMI in patients with MS (PwMS) and to investigate potential associations between the waist circumference (WC) and body mass index (BMI) and demographic and specific MS characteristics. Adhering to PRISMA guidelines, a detailed search of the MEDLINE PubMed, Cochrane Library, and Scopus databases was conducted. Results: A total of 16 studies were included. The pooled mean WC and BMI among PwMS was estimated to be 87.27 cm (95%CI [84.07; 90.47]) and 25.73 (95%CI [25.15; 26.31]), respectively. Meta-regression models established a significant bidirectional relationship between WC and the Expanded Disability Scale (EDSS) (p < 0.001) but not between BMI and EDSS (p = 0.45). Sensitivity analyses showed no association between WC and age (p = 0.48) and a tendency between WC and disease duration (p = 0.08). Conclusions: Although WC measurements classify PwMS as normal weight, BMI measurements classify them as overweight. Therefore, WC should complement BMI evaluations in clinical practice. Additionally, our findings highlight the significant association between abdominal fat, as indicated by WC, and disease progression. Considering the heightened risk of cardiovascular comorbidity and mortality among PwMS, we recommend integrating both WC and BMI as standard anthropometric measurements in routine clinical examinations and targeted prevention strategies for PwMS.

Prevalence and epidemiology of stroke in patients with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Epidemiological data are sparse regarding the risk of stroke in patients with multiple sclerosis (MS). OBJECTIVE: To estimate the following: (1) the pooled prevalence of all-cause stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) in MS patients; (2) the relative risk for all-cause stroke, AIS and ICH in MS patients compared to the general population; (3) associations between patient characteristics and the risk for AIS and ICH in MS patients. METHODS: Systematic review and meta-analysis of registry-based and cohort studies. RESULTS: Thirteen observational studies comprising 146,381 MS patients were included. The pooled prevalence of all-cause stroke was 2.7% (95% confidence interval [CI] 1.3-4.6%), with the relative risk of all-cause stroke being higher in MS patients compared to the general population (RR: 2.55; 95% CI 1.97-3.29). Subgroup analyses per stroke subtype revealed a pooled AIS prevalence of 2.1% (95% CI 0.8-4.1%) and a pooled ICH prevalence of 0.6% (95% CI 0.2-1.2%). Compared to the general population, patients with MS were found to harbour an increased risk for AIS (RR: 2.79; 95% CI 2.27-3.41) and ICH (RR: 2.31; 95% CI 1.04-5.11), respectively. The pooled prevalence of cardiovascular risk factors in MS patients was 11.5% (95% CI 2.9-24.7%) for dyslipidaemia, 18.2% (95% CI 5.9-35.3%) for hypertension and 5.4% (95% CI 2.1-10.2%) for diabetes. In meta-regression, age was negatively associated with AIS risk (ß = - .03, p = 0.04), with a 1-year increase in age resulting in a significant 3% (95%CI 0-5) attenuation of the risk of AIS. CONCLUSION: The findings of the present meta-analysis indicate that MS is associated with an increased risk for ischaemic and haemorrhagic stroke. Future well-designed epidemiological studies are warranted to corroborate the robustness of the present findings in the MS population.

Is vertebral artery hypoplasia a predisposing factor for posterior circulation cerebral ischemic events? A comprehensive review.

Vertebral artery hypoplasia is not currently considered an independent risk factor for stroke. Emerging evidence suggest that vertebral artery hypoplasia may contribute to posterior circulation ischemic events, especially when other risk factors coexist. In the present literature review, we present published data to discuss the relationship between a hypoplastic vertebral artery and posterior circulation cerebral ischemia. Despite difficulties and controversies in the accurate definition and prevalence estimation of vertebral artery hypoplasia, ultrasound studies reveal that the reduced blood flow observed ipsilateral to the hypoplastic vertebral artery may result in local cerebral hypoperfusion and subsequent focal neurological symptomatology. That risk of cerebral ischemia is related to the severity of the hypoplasia, suggesting that the smaller of paired arteries are more vulnerable to occlusion. Existing cohort studies further support clinical observations that hypoplastic vertebral artery enhances synergistically the vascular risk for posterior circulation ischemic events and is closely associated with both atherosclerotic and prothrombotic processes.

The Prevalence of Diabetes Mellitus Type II (DMII) in the Multiple Sclerosis Population: A Systematic Review and Meta-Analysis.

Introduction: The interactions between Diabetes Mellitus type II (DMII) and Multiple Sclerosis (MS) lead to higher levels of fatigue, higher risk of physical disability, faster cognitive decline, and in general a lower quality of life and a higher frequency of depression compared to the general population. All of the above accelerate the disability progression of patients with MS, reduce the patients' functional capacity, and further increase their psychological and economic burden. Methods: This systematic review and meta-analysis aims to calculate the prevalence of DMII in the MS population. Following PRISMA guidelines, a thorough search of the Medline Pubmed, Cochrane Library, and Scopus databases was performed, focusing on the frequency of DMII in the MS population. Results: A total of 19 studies were included in the synthesis. The results of the main meta-analysis of random effects using R studio 3.3.0 for Windows and the Meta r package showed that the prevalence of DMII in the MS population is 5% (95% CI [0.03, 0.07], 19 studies, I2 = 95%, pQ < 0.001). Additional subgroup analysis based on region showed a difference of 4.4% (I2 = 95.2%, pQ < 0.001), psubgroupdifference = 0.003) between European and non-European participants, while demographic- and MS-specific characteristic (EDSS, Disease Duration) did not seem to affect the prevalence of DMII in the MS population (p = 0.30, p = 0.539, p = 0.19, p = 0.838). No publication bias was discovered (Egger's p test value: 0.896). Conclusions: Even though the prevalence of DMII in the MS population is lower than 10% (the reported prevalence of DMII in the general population) the interactions between the two conditions create significant challenges for MS patients, their caregivers, and physicians. DΜΙΙ should be systematically recorded in the case of MS patients to clearly delineate any potential relationship between the two conditions. Additionally, more structured studies investigating the interactions of MS and DMΙΙ as well as the direction of the causation between those two conditions are necessary in order to gain a deeper insight into the nature of the interaction between MS and DMII.

The effects of HMG-CoA reductase inhibitors on disease activity in multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: To assess whether statins (3­hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert disease-modifying effects in multiple sclerosis (MS). APPROACH: A systematic review and meta-analysis was performed including randomized-controlled clinical trials (RCTs) on statin use in MS. A random-effects model was applied to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), when comparing patients treated with statins alone or adjunct to disease modifying treatment (DMT) to non-statin-treated patients. RESULTS: We identified 7 RCTs including 789 patients with relapsing-remitting MS (RRMS), all of whom received additional DMT with IFN-ß. Single identified RCTs in secondary-progressive MS (SPMS), clinically isolated syndrome (CIS) and optic neuritis (ON) were not meta-analyzed. In RRMS, add-on statin use was not associated with the risk of clinical relapse (OR=1.30, 95%CI: 0.901.87) or EDSS-progression from baseline, neither appeared related to the risk of new contrast-enhancing or T2 lesions (OR=1.28, 95%CI: 0.364.58), and the risk of whole-brain volume reduction on MRI. Add-on statins to IFN-ß were safe and well-tolerated. In SPMS, stand-alone simvastatin led to significantly reduced annualized rate of whole-brain volume reduction. In CIS and ON, statins were associated with reduced risk for new T2 lesions and improved visual recovery, respectively. CONCLUSIONS: We detected no benefit from statin treatment as add-on to IFN-ß in RRMS. However, a potential beneficial effect in SPMS, CIS and ON deserves independent confirmation and further evaluation within adequately powered RCTs.