Subacute thyroiditis in the SARS-CoV-2 era: a multicentre prospective study.

Objective: Many cases of subacute thyroiditis (SAT) have been described related to SARS-CoV-2 infection, but no prospective data about follow-up are known. This prospective, longitudinal, 3-year, multicentre study aims to explore the clinical peculiarities and outcome of SAT in relation to SARS-CoV-2 infection, ascertained with antibody dosage. Methods: All patients receiving SAT diagnosis from November 2020 to May 2022 were enrolled. Data on anamnesis, physical examination, blood tests (TSH, freeT4, freeT3, thyroglobulin, anti-thyroid antibodies, C-reactive protein, erythrocyte sedimentation rate, complete blood count), and thyroid ultrasound were collected. At baseline, the presence of IgG against the SARS-CoV-2 spike protein or nucleocapsid was investigated. Patients were evaluated after 1, 3, 6, and 12 months. Results: Sixty-six subjects were enrolled. At baseline, 54 presented with pain, 36 (67%) for at least 15 days. Serum SARS-CoV-2 IgG measurements documented that 7 out of 52 subjects (13.5%) had infection before SAT diagnosis (COVID+). No significant differences between the COVID+ and COVID- groups were found at baseline, except for respiratory symptoms and fever, which were more common in COVID+ (P = 0.039 and P = 0.021, respectively). Among the 41 subjects who completed follow-up, COVID+ and COVID- did not differ for therapeutic approach to SAT or outcome, all having an improvement in neck pain, inflammation parameters, and ultrasound features. Conclusion: This is the first prospective study investigating any difference both at diagnosis and at follow-up between SAT presentation in patients with previous SARS-CoV-2 infection and those without. Our data demonstrate that SARS-CoV-2 does not impact on SAT onset, evolution, and outcome.

Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.

BACKGROUND: Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop severe COVID-19. We conducted a systematic review of current evidence to investigate the association of genetic variants of these genes with the susceptibility to virus infection and patient prognosis. METHODS: We systematically searched Medline, Embase and The Cochrane Library for articles published until May 2022, and included observational studies covering genetic association of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes with COVID-19 susceptibility or prognosis. We evaluated the methodological quality of included studies, and pooled data as convenient in meta-analysis (MA). Odds ratio (OR) values and 95% confidence intervals were calculated. RESULTS: We included 35 studies (20 on ACE, 5 each on IFITM3, TMPRSS2, TNFα), enrolling 21,452 participants, of them 9401 were COVID-19 confirmed cases. ACE1 rs4646994 and rs1799752, ACE2 rs2285666, TMPRSS2 rs12329760, IFITM3 rs12252 and TNFα rs1800629 were identifies as common polymorphisms. Our MA showed an association between genetic polymorphisms and susceptibility to SARS-CoV-2 infection for IFITM3 rs12252 CC (OR 5.67) and CT (OR 1.64) genotypes. Furthermore, MA uncovered that both ACE DD (OR 1.27) and IFITM3 CC (OR 2.26) genotypes carriers had a significantly increased risk of developing severe COVID-19. DISCUSSION: These results provide a critical evaluation of genetic polymorphisms as predictors in SARS-CoV-2 infection. ACE1 DD and IFITM3 CC polymorphisms would lead to a genetic predisposition for severe lung injury in patients with COVID-19.

Real-World Data and Budget Impact Analysis (BIA): Evaluation of a Targeted Next-Generation Sequencing Diagnostic Approach in Two Orthopedic Rare Diseases.

Objective: Next-generation sequencing (NGS) technology, changing the diagnostic approach, has become essential in clinical settings, and its adoption by public health laboratories is now the practice. Despite this, as technological innovations, its intake requires an evaluation of both the clinical utility and the economic investment, especially considering the rare disease scenario. This study evaluated the analytical validity and the budget impact of an NGS-Ion Torrent™ approach for the molecular germline diagnosis of two musculoskeletal rare diseases. Methods: Two cohorts of 200 and 199 patients with suspect or clinical diagnosis of multiple osteochondromas (MO) and osteogenesis imperfecta (OI) previously evaluated with a single-gene diagnostic protocol were re-analyzed using a targeted NGS assay. Analytical validity was assessed by comparing NGS and single-gene protocol. A budget impact analysis using real-world cost data-considering the healthcare perspective- was performed by applying activity-based costing (ABC). The cost considered consumables, personnel, and equipment. Additional costs not related to NGS activities were not considered. Sensitivity analysis was performed. Results: The NGS method showed a higher (for MO) and comparable (for OI) diagnostic sensitivity than the traditional techniques, apart from always reducing the time and costs of diagnosis. Overall, the cost saving per patient is € 765 for OI and € 74 for MO. Materials represented the highest cost driver of the NGS process. A time saving-proportional to the panel size-has been assessed in both cases. Conclusions: Our targeted NGS diagnostic approach decreases time to diagnosis and costs, appearing to be beneficial and recommended both for patients and from a healthcare perspective in routine diagnosis also considering very small gene panels and a low patient flow. The adequate analytical sensitivity always required the additional Sanger sequencing step of the low- and non-covered regions. A more accurate strategy evaluation is suggested in the case of ultra-rare/complex diseases, large gene-panel, or non-reference diagnostic centers.

The NGS technology for the identification of genes associated with the ALS. A systematic review.

BACKGROUND: More than 30 causative genes have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS). The next-generation sequencing (NGS) is a powerful and groundbreaking tool to identify disease-associated variants. Despite documented advantages of NGS, its diagnostic reliability needs to be addressed in order to use this technology for specific routine diagnosis. MATERIAL AND METHODS: Literature database was explored to identify studies comparing NGS and Sanger sequencing for the detection of variants causing ALS. We collected data about patients' characteristics, disease type and duration, NGS and Sanger properties. RESULTS: More than 200 bibliographic references were identified, of which only 14 studies matching our inclusion criteria. Only 2 out of 14 studies compared results of NGS analysis with the Sanger sequencing. Twelve studies screened causative genes associated to ALS using NGS technologies and confirmed the identified variants with Sanger sequencing. Overall, data about more 2,000 patients were analysed. The number of genes that were investigated in each study ranged from 1 to 32, the most frequent being FUS, OPTN, SETX and VCP. NGS identified already known mutations in 21 genes, and new or rare variants in 27 genes. CONCLUSIONS: NGS seems to be a promising tool for the diagnosis of ALS in routine clinical practice. Its advantages are represented by an increased speed and a lowest sequencing cost, but patients' counselling could be problematic due to the discovery of frequent variants of unknown significance.

New Direct-Acting Antivirals for the Treatment of Patients With Hepatitis C Virus Infection: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: New direct-acting antiviral agents (DAAs) approved for the treatment of patients infected by Hepatitis C virus (HCV) are well tolerated and increase sustained virological response (SVR) rate. We summarize current evidence on the efficacy and safety from comparative randomized controlled trials (RCTs) of DAAs. METHODS: We systematically searched MEDLINE, Embase, Scopus, CENTRAL, and Lilacs as well as a list of reference literature. We included RCTs comparing DAAs with placebo or active control and reporting response rates and adverse events according to antiviral regimens. Risk ratios (RRs) were pooled as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. RESULTS: We included 28 RCTs, enrolling more than 7000 patients. The quality of evidence was generally low. Twelve-week treatment with DAAs in naïve patients significantly increased SVR12 and SVR24 compared with placebo (RR 1.4, 95% CI 1.3-1.6; RR 1.5, 95% CI 1.4-1.6, respectively). This means that for every 1000 patients, 240 or 260 more patients experienced SVR12 or SVR24 if treated with any DAAs. We could not find RCTs assessing progression of liver disease or development of hepatocellular carcinoma. DAAs were not associated with higher incidence of serious adverse events or discontinuation due to adverse events. CONCLUSIONS: This systematic review confirms that new DAAs are more effective in inducing SVR than placebo. Outside clinical trials, in real word, HCV cure with DAA regimens occurs in less than 90% of patients, so further comparative evaluations are needed to establish their long-term effects.

Does a high-fat diet affect the development and progression of osteoarthritis in mice?: A systematic review.

AIMS: The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice. METHODS: A literature search was performed in PubMed, Embase, Web of Science, and Scopus to find all studies on mice investigating the effects of HFD or Western-type diet on OA when compared with a control diet (CD). The primary outcome was the determination of cartilage loss and alteration. Secondary outcomes regarding local and systemic levels of proteins involved in inflammatory processes or cartilage metabolism were also examined when reported. RESULTS: In total, 14 publications met our inclusion criteria and were included in our review. Our meta-analysis showed that, when measured by the modified Mankin Histological-Histochemical Grading System, there was a significantly higher rate of OA in mice fed a HFD than in mice on a CD (standardized mean difference (SMD) 1.27, 95% confidence interval (CI) 0.63 to 1.91). Using the Osteoarthritis Research Society International (OARSI) score, there was a trend towards HFD causing OA (SMD 0.78, 95% CI -0.04 to 1.61). In terms of OA progression, a HFD consistently worsened the progression of surgically induced OA when compared with a CD. Finally, numerous inflammatory cytokines such as tumour necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and leptin, among others, were found to be altered by a HFD. CONCLUSION: A HFD seems to induce or exacerbate the progression of OA in mice. The metabolic changes and systemic inflammation brought about by a HFD appear to be key players in the onset and progression of OA.Cite this article: Bone Joint Res 2019;8:582-592.

Comparison of cryoballoon and radiofrequency ablation techniques for atrial fibrillation: a meta-analysis.

AIMS: To perform an updated meta-analysis to assess efficacy, safety and technical performance of pulmonary vein isolation using cryoballoon or radiofrequency catheter ablation in patients with paroxysmal or persistent atrial fibrillation. METHODS: In June 2017, databases and websites were systematically searched for systematic reviews, randomized controlled trials and observational studies reporting data on efficacy, safety and technical performance outcomes at follow-up at least 12 months. Researchers independently assessed records' eligibility, inclusion and methodological quality of included studies. RESULTS: Six randomized controlled trials and 25 observational studies - 11 853 patients were included. Studies on paroxysmal atrial fibrillation were 29 and included 11 635 patients. Meta-analysis results showed no difference between cryoballoon and radiofrequency in terms of recurrent atrial fibrillation [risk ratio 1.04, 95% confidence interval (CI) 0.98-1.10] or atrial tachyarrhythmias (risk ratio 1.04, 95% CI 1-1.08) and fluoroscopy time (mean difference -1.92 min, 95% CI -4.89 to 1.05). Cryoballoon ablation was associated with fewer reablations (risk ratio 0.79, 95% CI 0.64-0.98), lower incidence of pericardial effusion (risk ratio 0.52, 95% CI 0.31-0.89) and cardiac tamponade (risk ratio 0.33, 95% CI 0.18-0.62) and shorter total procedural time (mean difference -23.48 min, 95% CI -37.97; -9.02) but with higher incidence of phrenic nerve palsy (risk ratio 5.43, 95% CI 2.67-11.04). Prespecified subgroup analysis confirmed overall results as for freedom from atrial fibrillation and atrial tachyarrhythmias. Only two observational studies included patients with persistent atrial fibrillation, thus hindering any conclusion in this population. CONCLUSION: In patients with paroxysmal atrial fibrillation, cryoballoon and radiofrequency ablation produce similar results in terms of freedom from recurrent atrial fibrillation or atrial tachyarrhythmias but with a different safety profile, being cryoballoon ablation less associated with cardiac complications but more likely to cause phrenic nerve palsy.

The New Test for Monitoring Infliximab Therapy: From Laboratory to Clinical Practice.

BACKGROUND: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation. OBJECTIVES: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies. METHODS: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies. RESULTS: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006). CONCLUSIONS: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.

The impact of immunogenicity of TNFα inhibitors in autoimmune inflammatory disease. A systematic review and meta-analysis.

BACKGROUND: Monoclonal antibodies drugs directed against TNFα, TNFα inhibitors, are immunogenic, and consequent anti-drug antibodies (ADA) formation may decrease the functional drug concentration, resulting in a loss of response. We evaluated the impact of ADA on TNFα therapeutic response. METHODS: We considered studies enrolling adult patients affected by autoimmune inflammatory disease in therapy with TNFα inhibitors. We collected data about study and population characteristics, treatment dosage, determination of ADA and adverse events (AE). We combined data in meta-analysis, calculating risk ratios (RR) for each study. p-Values<0.05 were considered as statistically significant. Methodological quality was evaluated. Analyses were performed with the STATA 11 and RevMan 5.3 softwares. RESULTS: We included 34 studies enrolling 4273 patients. Of these, 794 (18.6%) developed ADA. Our analysis showed a significant reduction of response (RR 0.43, 95%CI 0.3-0.63) in patients with ADA respect to patients without, especially in patients treated with Infliximab (RR 0.37) or Adalimumab (RR 0.40). Furthermore, the administration of TNFα inhibitors produced a reaction at the infusion site in 17%, infection in 30% and serious AE in 5% of patients. CONCLUSION: Detectable ADA significantly reduced TNFα inhibitors response. Drug administration can also cause injection site reaction and infections. Early detection of serum ADA levels may improve patients' management. Currently, there are many indications about the use of immunogenicity tests to guide the therapy, but information regarding how to implement it in clinical practice is needed.

A systematic evaluation of immunoassay point-of-care testing to define impact on patients' outcomes.

Background Point-of-care testing has been developed to provide rapid test results. Most published studies focus on analytical performance, neglecting its impact on patient outcomes. Objective To review the analytical performance and accuracy of point-of-care testing specifically planned for immunoassay and to evaluate the impact of faster results on patient management. Methods A search of electronic databases for studies reporting immunoassay results obtained in both point-of-care testing and central laboratory scenarios was performed. Data were extracted concerning the study details, and the methodological quality was assessed. The analytical characteristics and diagnostic accuracy of six points-of-care testing: troponin, procalcitonin, parathyroid hormone, brain natriuretic peptide, C-reactive protein and neutrophil gelatinase-associated lipocalin were evaluated. Results A total of 116 scientific papers were analysed. Studies measuring procalcitonin, parathyroid hormone and neutrophil gelatinase-associated lipocalin reported a limited impact on diagnostic decisions. Seven studies measuring C-reactive protein claimed a significant reduction of antibiotic prescription. Several authors evaluated brain natriuretic peptide or troponin reporting faster decision-making without any improvement in clinical outcome. Forty-four per cent of studies reported analytical data, showing satisfactory correlations between results obtained through point-of-care testing and central laboratory setting. Half of studies defined the diagnostic accuracy of point-of-care testing as acceptable for troponin (median sensitivity and specificity: 74% and 94%, respectively), brain natriuretic peptide (median sensitivity and specificity: 82% and 88%, respectively) and C-reactive protein (median sensitivity and specificity 85%). Conclusions Point-of-care testing immunoassay results seem to be reliable and accurate for troponin, brain natriuretic peptide and C-reactive protein. The satisfactory analytical performance, together with an excellent practicability, suggests that it could be a consistent tool in clinical practice, but data are lacking regarding the patient outcomes.

Can NGAL be employed as prognostic and diagnostic biomarker in human cancers? A systematic review of current evidence.

BACKGROUND: Some studies have reported differentially altered neutrophil gelatinase-associated lipocalin (NGAL) levels in several malignancies. We evaluated NGAL measured in plasma or urine as both prognostic and diagnostic marker for different types of human tumors. METHODS: We performed systematic electronic searches in Medline, Embase and CRDTAS. Studies were included if they evaluated NGAL as a prognostic or diagnostic marker for human cancers. The selection of the studies, screening of the full texts and data extraction were conducted independently by 2 authors. We used the random-effects model for the meta-analyses. A methodological assessment was completed. RESULTS: We included 35 studies dedicated to colorectal, pancreas, breast, thyroid, gastric, kidney, endometrial, brain, liver, lung, esophageal, oral and ovarian cancers. Our meta-analyses showed that, in patients with colorectal and breast cancer, positive NGAL expression was associated with a decrease of disease-free survival (hazard ratio [HR] = 2.27, 95% confidence interval [95% CI], 1.54-3.36; HR = 1.78, 95% CI, 1.33-2.38, respectively). NGAL was a negative prognostic marker of overall survival in colorectal (HR = 2.37, 95% CI, 1.68-3.34) and endometrial (HR = 4.38, 95% CI, 1.9-10.12) cancers. Discriminative power of NGAL between cancer patients and control was moderate in colorectal cancer (area under the curve [AUC] = 0.6; pooled sensitivity 0.56; pooled specificity 0.72), acceptable in pancreatic cancer (AUC = 0.8; pooled sensitivity 0.6; pooled specificity 0.8) and good in thyroid cancer (AUC = 0.9; pooled sensitivity 0.85; pooled specificity 0.96). CONCLUSIONS: NGAL determination in plasma and urine could be useful in the prognosis of colorectal and breast cancer, but its prognostic accuracy remains uncertain for other human tumors.

Risk of malignancies using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis.

INTRODUCTION: Malignancies have been reported in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with anti-tumour necrosis factor (anti-TNF) agents. Areas covered: We conducted a systematic review of randomized controlled trials (RCTs) to determine the effect of anti-TNF agents on the occurrence of cancer (any type). Literature databases were searched up to May 2014 to identify relevant studies that evaluated adalimumab, certolizumab, etanercept, golimumab, or infliximab, compared with placebo or no treatment. Data on cancer occurrence were extracted at the maximum follow-up time reported. Expert opinion: Fifty-five RCTs with 20,631 patients met the eligibility criteria. Of these, 32 trials with 15,539 patients reported at least one case of cancer, for a total of 112 malignancies. The degree of variability between studies was consistent with what would be expected to occur by chance alone. There was no evidence of an association between anti-TNF agents and cancer risk (fixed-effects model (OR: 1.31, 95% CI: 0.89, 1.95); a random-effects model (OR: 1.16, 95% CI: 0.75, 1.81)). We found evidence of selective outcome reporting or publication bias suggesting that the pooled effect estimate for cancer may have been overestimated. The evidence is imprecise, and the risk of bias was high or unclear across primary studies.

Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis.

INTRODUCTION: Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.

Clinical utility of the (-2)proPSA and evaluation of the evidence: a systematic review.

BACKGROUND: Diagnostic studies usually provide important information about the analytical and diagnostic performances. We investigated the clinical utility of (-2)proPSA in identifying patients with prostate cancer (PCa). METHODS: We performed electronic searches in five databases as well as a list of reference literature. Studies were included if they evaluated the diagnostic accuracy of (-2)proPSA in men with PSA value ranged from 2.0 to 10 µg/L. We also analyzed data about total PSA (tPSA), %(-2)proPSa, freePSA (fPSA), its percentage (%fPSA) and the prostate health index (phi). The selection of the studies, the screening of the full texts and the data extraction, as well as the assessment of risk of bias using the QUADAS-2 tool were conducted independently by two authors. Grading the quality of the evidence was carried out according to the GRADE method. The random effects model was used for the meta-analyses. RESULTS: We included 17 studies, including 6912 patients. The pooled sensitivity of (-2)proPSA was 90% and the summary specificity was 13%. The tPSA sensitivity and specificity were 89% and 25%, respectively. Considering (-2)proPSA, 225 men out of 1000 have been identified having PCa true positives (TP). However, 652 persons have been incorrectly identified and undergo biopsy. The majority of studies were judged to carry a moderate risk of bias. Therefore, the overall quality of evidences was deemed to be low. CONCLUSIONS: The (-2)proPSA could be useful to identify men at risk of PCa, but its accuracy still remains uncertain and the level of evidence does not support an improved clinical utility.

The prognostic role of bone turnover markers in multiple myeloma patients: The impact of their assay. A systematic review and meta-analysis.

BACKGROUND: Multiple myeloma (MM) is characterized by the progressive destruction of bone tissue due to the uncontrolled proliferation of the immunoglobulins. The detection of bone turnover markers (BTMs) may represent a non-invasive method to assess the bone involvement and to predict the risk of bone morbidity. This systematic review evaluates clinical utility of changes in BTMs levels in MM patients and their prognostic role. METHODS: We searched Medline, Embase, WOS and Scopus. All eligible articles were examined and the risk of bias was evaluated. Results about PICP, PINP, ICTP, OC, CTX, NTX, RANKL and OPG were extracted. Weighted mean difference, risk ratio and hazard ratio were pooled. RESULTS: Thirty studies and more than 2500 patients were included in this systematic review. The majority of them (50%) used ELISA to quantify BTMs, 10 of them used RIA and only 4 did not report the information regarding the type of immunoassays. In MM patients, the concentration of NTX and ICTP increased, instead the concentrations of BAP and OC lowered when compared to healthy subjects. High levels of ICTP were predictive of bone events (RR 1.18) and they were associated to poor survival (HR 1.08). Most of the included studies were considered at high risk of bias, in fact the reporting of the results was often incomplete. Between-studies heterogeneity was high. CONCLUSIONS: BTMs measurement may be very useful in the management of MM patients, especially to evaluate the bone disease progression. They could help clinicians to identify patients at high risk of bone events and to opt for more appropriate therapy; nevertheless their high biological and analytical variability limit their implementation in clinical practice.

Remote magnetic with open-irrigated catheter vs. manual navigation for ablation of atrial fibrillation: a systematic review and meta-analysis.

The aim of this study was to determine the efficacy and safety of remote magnetic navigation (RMN) with open-irrigated catheter vs. manual catheter navigation (MCN) in performing atrial fibrillation (AF) ablation. We searched in PubMed (1948-2013) and EMBASE (1974-2013) studies comparing RMN with MCN. Outcomes considered were AF recurrence (primary outcome), pulmonary vein isolation (PVI), procedural complications, and data on procedure's performance. Odds ratios (OR) and mean difference (MD) were extracted and pooled using a random-effect model. Confidence in the estimates of the obtained effects (quality of evidence) was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. We identified seven controlled trials, six non-randomized and one randomized, including a total of 941 patients. Studies were at high risk of bias. No difference was observed between RMN and MCN on AF recurrence [OR 1.18, 95% confidence interval (CI) 0.85 to 1.65, P = 0.32] or PVI (OR 0.41, 95% CI 0.11-1.47, P = 0.17). Remote magnetic navigation was associated with less peri-procedural complications (Peto OR 0.41, 95% CI 0.19-0.88, P = 0.02). Mean fluoroscopy time was reduced in RMN group (-22.22 min; 95% CI -42.48 to -1.96, P = 0.03), although the overall duration of the procedure was longer (60.91 min; 95% CI 31.17 to 90.65, P < 0.0001). In conclusion, RMN is not superior to MCN in achieving freedom from recurrent AF at mid-term follow-up or PVI. The procedure implies less peri-procedural complications, requires a shorter fluoroscopy time but a longer total procedural time. For the low quality of the available evidence, a proper designed randomized controlled trial could turn the direction and the effect of the dimensions explored.

Timing matters in hip fracture surgery: patients operated within 48 hours have better outcomes. A meta-analysis and meta-regression of over 190,000 patients.

BACKGROUND: To assess the relationship between surgical delay and mortality in elderly patients with hip fracture. Systematic review and meta-analysis of retrospective and prospective studies published from 1948 to 2011. Medline (from 1948), Embase (from 1974) and CINAHL (from 1982), and the Cochrane Library. Odds ratios (OR) and 95% confidence intervals for each study were extracted and pooled with a random effects model. Heterogeneity, publication bias, bayesian analysis, and meta-regression analyses were done. Criteria for inclusion were retro- and prospective elderly population studies, patients with operated hip fractures, indication of timing of surgery and survival status. METHODOLOGY/PRINCIPAL FINDINGS: There were 35 independent studies, with 191,873 participants and 34,448 deaths. The majority considered a cut-off between 24 and 48 hours. Early hip surgery was associated with a lower risk of death (pooled odds ratio (OR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; P<0.000) and pressure sores (0.48, 95% CI 0.38 to 0.60; P<0.000). Meta-analysis of the adjusted prospective studies gave similar results. The bayesian probability predicted that about 20% of future studies might find that early surgery is not beneficial for decreasing mortality. None of the confounders (e.g. age, sex, data source, baseline risk, cut-off points, study location, quality and year) explained the differences between studies. CONCLUSIONS/SIGNIFICANCE: Surgical delay is associated with a significant increase in the risk of death and pressure sores. Conservative timing strategies should be avoided. Orthopaedic surgery services should ensure the majority of patients are operated within one or two days.