Individual Patient Data Meta-Analysis of 10-Year Follow-Up after Endovascular and Open Repair for Ruptured Abdominal AorticAneurysms.

BACKGROUND: Endovascular aortic repair (EVAR) has conferred an early survival advantage compared to an open surgical repair (OSR) in patients with ruptured abdominal aortic aneurysms (rAAA). However, the long-term survival benefit after EVAR was not displayed among randomized controlled trials (RCTs), whereas many non-RCTs have provided conflicting results. We conducted a time-to-event individual patient data (IPD) meta-analysis on long-term rAAA data. METHODS: All studies comparing mortality after EVAR versus OSR for rAAA were included. We used restricted mean survival times (RMSTs) as a measure of life expectancy for EVAR and OSR. RESULTS: A total of 21 studies, including 12,187 patients (4952 EVAR and 7235 OSR) were finally deemed eligible. A secondary IPD analysis included 725 (372 EVAR and 353 OSR) patients only from the 3 RCTs (Immediate Management of the Patient With Rupture : Open Versus Endovascular Repair, Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus and Amsterdam Acute Aneurysm Trial trials). Among all studies, the median survival was 4.20 (95% confidence interval [CI]: 3.70-4.58) years for EVAR and 1.91 (95% CI: 1.57-2.39) years for OSR. Although EVAR presented with increased hazard risk from 4 to 7 years, which peaked at 6 years after the operation, the RMST difference was 0.54 (95% CI: 0.35-0.73; P < 0.001) years gained with EVAR at the end of the 10-year follow-up. IPD meta-analysis of RCTs did not demonstrate significant differences. CONCLUSIONS: At 10-years follow-up, EVAR was associated with a 6.5 month increase in life expectancy when compared to OSR after analyzing all eligible studies. Evidence from our study suggests that a strict follow-up program would be desirable, especially for patients with long-life expectancy.

A randomized controlled trial evaluating the short-term efficacy of a single-administration intramuscular injection with the fixed combination of thiocolchicoside-diclofenac versus diclofenac monotherapy in patients with acute moderate-to-severe low back pain.

BACKGROUND: Non-specific acute low back pain (LBP) is a common health problem that may be accompanied by muscle spasm and decreased mobility. The combination of non-steroidal anti-inflammatory drugs and muscle relaxants represents an advantageous therapeutic option, however, available data on their combined use are conflicting. This prospective, randomized, single-blind, two-parallel-group trial assessed the efficacy of a single intramuscular (IM) injection of the fixed-dose combination (FDC) diclofenac (75 mg)-thiocolchicoside (4 mg/4 ml) product (test treatment) compared to diclofenac (75 mg/3 ml) alone (reference treatment) for the symptomatic relief of acute LBP. Tolerability and safety were also assessed as secondary variables. METHODS: One hundred thirty-four patients were enrolled (safety population) and randomly allocated to the combination or single-agent regimen. Pain intensity and muscle spasm, assessed respectively by the patient-reported visual analogue scale and investigator-performed finger-to-floor distance test, were determined prior to the injection as well as 1 and 3 h post-injection in 123 patients (per-protocol population). The patients were blinded to treatment. Safety was assessed up to 24 h post-injection. RESULTS: The test treatment was superior in both alleviating the pain intensity and reducing the finger-to-floor distance at both 1 (p < 0.01 and p = 0.023 respectively) and 3 h post-injection (p < 0.01). A higher percentage of patients experienced > 30% reduction in pain intensity at 1 and 3 h with the test treatment (p = 0.037 and p < 0.01 respectively). The corresponding VAS (SD) scores for the test treatment group were at baseline, 1 and 3 h post-injection 72.03 (± 11.72), 45.37 (± 16.28) and 31.56 (± 15.08) respectively and for the reference treatment group 65.20 (± 12.16), 48.98 (± 18.76) and 44.52 (± 17.33) respectively. No adverse effects were reported with the combination treatment, whereas two patients treated with diclofenac reported dizziness. CONCLUSIONS: The FDC treatment is an effective and well-tolerated option for the symptomatic treatment of LBP. Clinical and patient-reported assessments confirmed that a single IM injection of FDC diclofenac-thiocolchicoside was more effective than diclofenac alone in conferring rapid and sustained improvement in mobility and pain intensity. TRIAL REGISTRATION: EudraCT No: 2017-004530-29 Available at https://eudract.ema.europa.eu/ Registered 04 Dec 2017.

A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis.

BACKGROUND: Ectoine is a widespread osmolyte enabling halophilic bacteria to withstand high osmotic stress that has many potential applications ranging from cosmetics to its use as a therapeutic agent. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of ectoine 1% and hyaluronic acid 0.1% containing (EHA) cream with a vehicle cream in children with mild-to-moderate atopic dermatitis (AD). METHODS: A randomized, controlled, observer-blind, multicenter clinical trial was conducted in children aged 2-18 years, diagnosed with mild-to-moderate AD (SCORAD ≤20). Patients were randomized to either receiving EHA cream or vehicle cream twice daily for 4 weeks. The primary outcome measure was the mean change in objective SCORAD from baseline to the final visit. The secondary outcome measures included the mean change in Investigator's Global Assessment score, patient's judgment of efficacy and patient's assessment of pruritus. Safety of EHA cream was also assessed. RESULTS: A total of 70 patients (35 in each group) were randomized and 57 were included in the final analysis set. Based on SCORAD measurements, patients using EHA cream achieved superior clinical improvement compared to the control group at 28 days (p < .001). EHA cream was also superior to the vehicle cream regarding all secondary outcome measures. Eight (23.5%) patients receiving EHA cream and two (5.7%) patients receiving vehicle cream experienced mild cutaneous adverse events (AEs). CONCLUSIONS: In children 2-18 years old with mild-to-moderate AD, EHA cream was superior to vehicle cream, with minor AEs.

A systematic review and meta-analysis of interventional studies of bisphosphonates and denosumab in multiple myeloma and future perspectives.

Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodronate (CLOD) and zoledronic acid (ZOL) were effective in reducing skeletal complications compared to placebo. Results are mixed regarding the efficacy of pamidronate in reducing skeletal related events. ONJ rates were higher for ZOL, but under 5%, with CLOD having the safest profile. DENOS demonstrated non-inferiority to ZOL, in improving overall survival [pooled Hazard Ratio(HR) 1.02(95% CI 0.72,1.44)], progression free survival [pooled HR 0.92(95% CI 0.76,1.11)] and in reducing skeletal related events [pooled HR 1.03(95% CI 0.92,1.16)], with similar rates of ONJ and better safety profile regarding renal toxicity. Denosumab has comparable efficacy and safety with ZOL and may even replace BPs in the future, in the management of myeloma bone disease.

Non-Doppler hemorrhoidal artery ligation and hemorrhoidopexy combined with pudendal nerve block for the treatment of hemorrhoidal disease: a non-inferiority randomized controlled trial.

BACKGROUND: In this study, we proposed a combined outpatient treatment modality for hemorrhoidal disease. METHODS: This study was a prospective non-inferiority randomized controlled trial (RCT). The experimental group included the dearterialization and hemorrhoidopexy under pudendal nerve block, whereas the comparator consisted of the standard Doppler guided hemorrhoidal artery ligation and hemorrhoidopexy, under spinal anesthesia. As primary hypothesis, we considered the non-inferiority of the proposed modality in terms of the presenting symptom remission rate (non-inferiority margin: 10%). Randomization was based on a 1:1 ratio. Blinding was confined to the patient and the investigator. RESULTS: Overall, 60 patients were enrolled. The primary hypothesis of this RCT (96.7% vs 73.3%) was validated. The experimental group was associated with a lower operation duration and an expedited onset of mobilization and feeding. Moreover, a favorable profile regarding short-term morbidity and analgesia was identified. The control group displayed a higher pile recurrence rate and a suboptimal patient satisfaction. A significant effect of the treatment modality in most of the SF-36 components was confirmed. CONCLUSIONS: The proposed treatment modality was associated with favorable short and long-term outcomes. Due to specific limitations, further RCTs, with a larger sample size, are required. Trial Registration ClinicalTrials.gov : NCT03298997.

Association of assisted reproductive technology with autism spectrum disorder in the offspring: an updated systematic review and meta-analysis.

This study aims to provide an up-to-date meta-analysis of data from studies investigating the risk of bearing a child with autism spectrum disorder (ASD) after being conceived by assisted reproductive technology (ART). The study was conducted according to the PRISMA Statement. PubMed and Scopus databases were searched up to August 2, 2020. Observational studies using a type of conception of assisted reproductive technology and examined as outcome offspring with ASD were included. A random effect model was applied due to the heterogeneity of the studies. Statistical analysis was performed with Stata 13 software. The Newcastle-Ottawa scale was used to assess the methodological quality of the included studies. The search strategy identified 587 potentially relevant studies. A total of 15 studies provided adequate data for statistical comparisons and, therefore, were included in the meta-analysis. Analysis of the subset of studies that examined all offspring and controlled for confounder factors revealed that the use of ART is associated with a higher risk of ASD (RR = 1.11, 95% CI = 1.03-1.19, p < 0.009), while in the case of studies that focused on singletons, a statistically significant association between ART and ASD was not observed (RR = 0.96, 95% CI = 0.82-1.13, p = 0.654).Conclusion: The present meta-analysis confirmed the existing positive correlation between ART and ASD in offspring, suggesting that ART is correlated with a higher risk for bearing a child with ASD. In contrast, this relationship is not confirmed in singletons. High quality prospective studies with a larger number of participants are still required. What is Known: • Studies that investigated the association between ART and ASD in offspring have shown conflicting results. • A previous meta-analysis showed that offspring conceived by ART are 1.35 times more likely to develop ASD than offspring spontaneously conceived. What is New: • This investigation separately considered studies with and without adjustment for confounders. • The findings from the two analyses were similar.

Analysis of the quality of reporting of randomized controlled trials in anticoagulant versus antiplatelet medication for venous thromboembolism prophylaxis as governed by the CONSORT statement.

Randomized controlled trials (RCTs) are the gold standard research in evaluating healthcare interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement improves the quality of RCTs in an evidence-based approach. To evaluate the reporting quality of published RCTs concerning the use of anticoagulants versus antiplatelet agents for venous thromboembolism prophylaxis according to the CONSORT statement. Electronic databases were searched for English-language RCTs involving patients who received either anticoagulant or antiplatelet medication for prophylaxis of deep vein thrombosis and pulmonary embolism published from 2000 to 2019. Trials were considered eligible when the included patients received either anticoagulant or antiplatelet medication for primary and secondary prevention of deep vein thrombosis or pulmonary embolism and were randomly assigned to at least two treatment arms. Quality of reporting was assessed using a 37-item questionnaire based on the CONSORT 2010 checklist. Reporting was assessed in 2 publication periods (2000-2009) and (2010-2019). The effect of CONSORT statement in high- and low-ranked medical journals, according to their impact factor, has also been evaluated. The search identified 13 eligible articles for analysis. Only 12 of the 37 items of the checklist were addressed in 75% or more of the studies. Most items concerning the methodological issues were reported by fewer than 50% of the studies. Improvements over time were seen for items that assessed the methodological quality with no statistically significant difference. RCTs published in high-ranked journals showed better quality of reporting. Quality of reporting in RCTs focusing on the use of anticoagulants versus antiplatelet agents for venous thromboembolism prophylaxis remains unsatisfactory. Further improvement of reporting is necessary to assess the validity of clinical research.

Intravenous sodium valproate in status epilepticus: review and Meta-analysis.

Objective: Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use of intravenous sodium valproate (VPA) in SE.Methods: MEDLINE and Cochrane databases were comprehensively searched, while retrieved RCTs and meta-analyses were manually screened. Prespecified outcome measures included seizure-cessation, 24 h-efficacy, constitute (liver enzyme increase, arrhythmias, bone-marrow suppression, hypotension and respiratory depression) and severe (life-threatening) adverse events (AEs). Evidence synthesis was performed when appropriate, using Random-Effects (RE) or Fixed-Effects (FE) model based on heterogeneity between trials (homogeneity assumed when PQ > 0.1 and I2 < 50%). Outcomes were assessed using Odds-Ratios (ORs) and 95%Confidence-Intervals (95% CIs). Every available comparison was investigated in terms of efficacy and tolerability.Results:Thirteen studies were retrieved and five comparisons were available, four of which involved two or more studies. Results were compatible with no significant difference between VPA and Phenytoin both in terms of efficacy and tolerability [seizure-cessation: FE-OR = 1.99, 95% CI = (0.83-4.75), 24 h-efficacy: FE-OR = 1.32, 95% CI = (0.60-2.89), composite AEs: FE-OR = 0.45, 95% CI = (0.17-1.21)]. Phenobarbital proved more commonly associated with composite AEs than VPA [seizure-cessation: RE-OR = 0.68, 95% CI = (0.05-9.44), 24 h-efficacy: RE-OR = 0.88, 95% CI = (0.02-33.9), composite AEs: FE-OR = 0.26, 95% CI = (0.09-0.82), severe AEs: FE-OR = 0.30, 95% CI = (0.04-2.28)]. Diazepam was determined inferior to VPA concerning safety issues [seizure-termination: FE-OR = 0.77, 95% CI = (0.34-1.79), severe respiratory depression: FE-OR = 0.06, 95% CI = (0.01-0.48), severe hypotension: FE-OR = 0.09, 95% CI = (0.01-0.72)]. The combination of Lorazepam (LZP) with VPA and the combination of LZP with Levetiracetam presented no difference in efficacy [24h-efficacy: FE-OR = 0.68, 95% CI = (0.37-1.24)].Conclusions: Although, additional high-quality RCTs are warranted, according to our results, VPA can be considered a safe and effective option in the management of SE.

A SYSTEMATIC REVIEW OF OBSERVATIONAL STUDIES ASSESSING THE IMPACT OF OXIDATIVE STRESS IN COGNITIVE DECLINE.

OBJECTIVE: Introduction: Cognitive functions are defined as the mental processes through which information is received, processed, stored, and retrieved. Oxidation is considered as an important factor that affects negatively the brain function. The aim: To assess the impact of oxidative stress, as it is measured by oxidative markers or by the presence of anti-oxidants, on cognitive decline. PATIENTS AND METHODS: Materials and methods: A systematic review of published observational studies in PubMed and in Scopus was performed. During the review process the keywords were used as follows: ("oxidative stress") AND ("cognitive decline" OR "cognitive dysfunction" OR "cognitive impairment" OR "cognitive deficiency") AND ("observational study" OR "cross sectional study" OR "prospective study" OR "retrospective study" OR "cohort study"). The search was conducted for the years from 2016 to 2020. CONCLUSION: Conclusions: Seventy-four eligible studies were identified. Thirteen studies met the inclusion and quality criteria and were included in the systematic review. The studies conducted in ten different countries. Information about oxidative stress biomarkers is available in eight studies, while information about antioxidant factors is in ten studies. In all the thirteen studies the cognitive function was assessed with specific tools - scales. In the majority of studies, the presence of high scores in oxidative markers was positively associated with cognitive decline, while higher levels of antioxidant markers were associated with better cognitive function. Our results indicate that oxidative stress may be significantly associated with cognitive decline. The presence of the antioxidants glutathione, uric acid, melatonin, cysteine and peroxide dismutase has a positive effect on cognitive function.

Piezoelectric or Conventional Osteotomy in Rhinoplasty? A Systematic Review and Meta-Analysis of Clinical Outcomes.

INTRODUCTION: Osteotomy of nasal bones in rhinoplasty is associated with postsurgical morbidities. Recent evidence has suggested that a surgical method applying piezoelectric ultrasound waves for nasal osteotomies in rhinoplasty reduces soft tissue damage and causes less postsurgical morbidities compared to conventional methods. The purpose of this study is to compare clinical outcomes of piezoelectric and conventional lateral nasal osteotomies in rhinoplasty. METHODS: We searched PubMed, CENTRAL, and Web of Science up to 17 August 2019 for studies comparing postoperative outcomes of piezoelectric and conventional lateral osteotomies in rhinoplasty. We included studies comparing results of patients subjected to piezoelectric or conventional lateral nasal osteotomies in rhinoplasty. For outcomes, we considered postoperative pain, eyelid edema, periorbital ecchymosis, and intraoperative mucosal injury. RESULTS: For eyelid edema, a statistically significant difference in favor of piezoelectric osteotomy was documented within the first 3 postoperative days (standardized mean difference [SMD] = -0.65; 95% CI = -1.18, -0.12, p = 0.02; I2 = 69%) and on postoperative day 7 (SMD = -0.69; 95% CI = -1.47, -0.09; p = 0.08; I2 = 85%). This was also the case for periorbital ecchymosis within the first 3 postoperative days (SMD = -0.85; 95% CI = -1.42, -0.28; p = 0.004; I2 = 72%) and on postoperative day 7 (SMD = -0.52; 95% CI = -0.79, -0.24; p = 0.0003; I2 = 71%). Intraoperative mucosal injury (OR = 0.06; 95% CI = 0.01, 0.53; p = 0.01; Ι2 = 0%) and postoperative pain (SMD = -0.99; 95% CI = -1.78, -0.11; p = 0.01; I2 = 49%) were also statistically lower during piezoelectric osteotomies. CONCLUSIONS: This study shows that lateral piezoelectric osteotomy in rhinoplasty decreases postoperative pain, edema, ecchymosis, and intraoperative mucosa injuries compared to the conventional osteotomy technique with a chisel. Piezoelectric osteotomies are especially associated with less postoperative edema and ecchymosis in osteotomies not executed under direct vision.

SLC2A1 Tag SNPs in Greek Patients with Diabetic Retinopathy and Nephropathy.

Backround: Genetic variants are implicated in the development of diabetic retinopathy (DR) and nephropathy (DN). The role of solute carrier family 2-facilitated glucose transporter member 1 (SLC2A1), also known as glucose transporter (GLUT1), on DR and DN remain controversial. OBJECTIVE: Examination of the influence of tag SLC2A1 single-nucleotide polymorphisms (SNPs) on the development of DR and DN during the course of type 2 diabetes mellitus (T2DM). METHODS: A total of 169 patients with DR or DN, 107 uncomplicated T2DM patients, and 315 controls were recruited and genotyped for 14 SLC2A1 tag SNPs. SNPs and haplotypes were tested for associations with microvascular diabetes' complications. RESULTS: rs3768029 TT genotype was associated with a lower risk of DR + DN, compared to the CC wild-type (p = 0.0024). Moreover, CT and TT rs841847 genotypes were associated with a higher risk of DR + DN compared to the CC genotype (p = 0.0028). A common haplotype (GGCCCGCATCAAT) was associated with an increased risk of DR, DN, DR ± DN, and DR + DN phenotypes. Mutational loads of rs3768029, rs3729548, rs841853, and rs841847 were found to influence the development of microvascular complications during the T2DM course. CONCLUSIONS: This study provides evidence that SLC2A1 gene variants might be implicated in the development of T2DM microvascular complications.

Assessing the reporting quality of systematic reviews of observational studies in preeclampsia.

PURPOSE: The majority of epidemiological studies in preeclampsia are observational and the overview of these studies is expressed by systematic reviews (SRs). The aim of this study was to evaluate the reporting quality of published SRs of observational studies (OS) in preeclampsia based on Meta-analysis of Observational Studies in Epidemiology (MOOSE) statement. METHODS: PubMed and Cochrane databases were searched for SRs of OS in preeclampsia published from 1st January 2011 through 10th December 2017. The SRs were evaluated for their reporting quality according to the MOOSE statement, an evidence-based tool which consists of a checklist of 35 items, overall and according to the ranking of journals. RESULTS: The search identified 93 eligible SRs. Six items were reported in all the studies. Ninety percent (90%) and 70% of the studies complied with 13 (37%) and 20 (57%) items of MOOSE, respectively. Two items concerning search strategy were under-reported (< 10% of studies). High-ranked journals (impact factor ≥ 5) presented a better reporting quality (p < 0.05) of the MOOSE items, while no significant differences were identified in individual items. CONCLUSIONS: The quality of reporting of SRs for OS in preeclampsia was considered satisfactory; though, ranking of journals may have an effect in reporting. Further improvement of reporting is necessary to enhance the validity of SRs.

Variants of the elastin (ELN) gene and susceptibility to intracranial aneurysm: a synthesis of genetic association studies using a genetic model-free approach.

BACKGROUND: The presence of an intracranial aneurysm (IA) is thought to have a genetic origin. The genetic association studies (GAS) that investigated the association between IA and elastin gene (ELN) variants have produced contradictory or inconclusive results. MATERIALS AND METHODS: In order to decrease the uncertainty of estimated genetic risk effects, a meta-analysis of published GAS-related variants in the ELN gene (ELN INT20 1315T > C, EX20 1264G > A, INT23 1501 + 24T > C and INT4 196 + 71G > A) with susceptibility to IA was conducted using a genetic model-free approach. The risk effects were estimated using the generalized odds ratio (ORG) metric. RESULTS: The analysis showed significant association for the INT20 1315T > C variant [ORG = 0.66 (0.45-0.95)], indicating a protection effect. For the variants EX20 1264G > A, INT23 1501 + 24T > C and INT4 196 + 71G > A, no statistically significant association with IAs was found. CONCLUSION: There is evidence that the ELN variant INT20 1315T > C is implicated in the development of IA; however, the results should be interpreted with caution since the number of published studies is limited.

Bioavailability, Efficacy and Safety of Generic Immunosuppressive Drugs for Kidney Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney transplant recipients. We conducted a meta-analysis of trials examining the bioavailability of generic (test) immunosuppressive drugs relative to their brand (reference) counterparts in healthy volunteers, based on the US Food and Drug Administration requirements for approval of generics, and their efficacy and safety in kidney transplant recipients. METHODS: Eligible studies were identified in PubMed, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, and conference abstracts. RESULTS: Twenty crossover trials of healthy volunteers (n = 641) and 6 parallel-arm randomized controlled trials of kidney transplant recipients (n = 594) were identified. The 90% CI of the pooled test-to-reference drug ratio for maximum or peak plasma concentration (Cmax) and area under the plasma concentration time-curve from time 0 to time of last determinable concentration (AUC(0-t)) fell within the required range (0.80-1.25) for cyclosporine (Cmax 0.91; 90% CI 0.86-0.95; and AUC(0-t) 0.97; 90% CI 0.94-1.00), tacrolimus (Cmax 1.17; 90% CI 1.09-1.24; and AUC(0-t) 1.00; 90% CI 0.97-1.03) and mycophenolate mofetil (Cmax 0.98; 90% CI 0.96-1.01; and AUC(0-t) 1.00; 90% CI 0.99-1.01). In subgroup analyses, some generic cyclosporine formulations did not meet criteria for bioequivalence. No significant differences were observed in the time to maximum plasma concentration and terminal plasma half-life between generic and brand drugs. In parallel-arm trials, generic cyclosporine was non-inferior to brand counterpart in terms of acute allograft rejection, infections, and death. CONCLUSIONS: Not all generic immunosuppressive drugs have similar relative bioavailability to their brand name counterparts. Evidence on their efficacy and safety is inconclusive. Tighter regulatory requirement for approval of generic drugs with narrow therapeutic index is needed.

FcγRIIa-H131R variant is associated with inferior response in diffuse large B cell lymphoma: A meta-analysis of genetic risk.

PURPOSE: Low-affinity variants FcγRIIIa-V158F and FcγRIIa- H131R may alter response to rituximab-based chemotherapy in diffuse large B-cell lymphoma (DLBCL) but available clinical evidence is inconclusive. Our purpose was to explore their association in terms of treatment response. METHODS: We performed a meta-analysis of published literature to associate these variants with complete remission after upfront immunochemotherapy in DLBCL, and summarized the genetic risk using the model-free approach of generalized odds ratio (ORG). PubMed and EMBASE search (up to July 2014) yielded five pertinent studies. RESULTS: FcγRIIa-H131R was associated with an inferior response to treatment (ORG 0.67; 95%CI 0.46-0.97) and an additive mode of inheritance, with the genetic risk of heterozygotes assigned in the middle between high affinity (H/H) and lower affinity (R/R) genotypes. This effect was unrelated to risk stratification, as no association was documented for FcγRIIa-H131R variant with the international prognostic index (IPI) (ORG 1.02; 95%CI 0.79-1.31 for IPI 3-5 over 0-2). FcγRIIIa-V158F had no impact on treatment response but linkage disequilibrium and defective antibody-dependent cell-mediated cytotoxicity may have affected the outcome. CONCLUSION: FcγRIIa-H131R but not FcγRIIIa-V158F may modify treatment response in DLBCL.

On-treatment prediction of sustained response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B patients.

BACKGROUND & AIMS: We assessed predictors of response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a in routine clinical practice. METHODS: Ninety-five HBeAg-negative patients received peginterferonalfa-2a for 48 weeks and were followed-up for 48 weeks post-treatment. Serum HBsAg and HBV DNA levels were monitored during and after therapy with valid commercial assays. Sustained response (SR) was defined as HBV DNA <2000 IU/ml at study week 96. RESULTS: Twenty-two patients (23%) achieved SR and nine (9.5%) lost HBsAg. HBsAg decline was more profound in patients with SR. HBsAg decline ≥10% from baseline to week 24 was significantly associated with SR [81% (17/21) vs 37% (21/57); Odds ratio: 7.286 (2.162-24.552), P = 0.001]. The PARC rule (no decrease in HBsAg and <2 log drop in HBV DNA at week 12) was evaluated in a subset of 47 patients. Among eight patients who fulfilled the PARC rule, none achieved SR. Of the 39 patients who did not fulfil the PARC rule, 24 (62%) had HBsAg decline of ≥10% at week 24 (12 achieved SR) and 15 (38%) had HBsAg decline of <10% (1 achieved SR; negative predictive value: 93%). CONCLUSIONS: In HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a, HBsAg decline >10% at 24 weeks is significantly associated with SR. The combination of the PARC rule and week 24 decline in HBsAg can identify almost two-thirds of patients who are unlikely to achieve SR. Clinicaltrials.gov identifier: NCT01283074.

Telomere Length in Peripheral Blood Mononuclear Cells of Patients on Chronic Hemodialysis Is Related With Telomerase Activity and Treatment Duration.

Telomere shortening to a critical limit is associated with replicative senescence. This process is prevented by the enzyme telomerase. Oxidative stress and chronic inflammation are factors accelerating telomere loss. Chronic hemodialysis, typically accompanied by oxidative stress and inflammation, may be also associated with replicative senescence. To test this hypothesis, we determined telomere length and telomerase activity in peripheral blood mononuclear cells (PBMCs) in a cross-sectional study. Hemodialysis patients at the University Hospital Larissa and healthy controls were studied. Telomere length was determined by the TeloTAGGG Telomere Length Assay and telomerase activity by Telomerase PCR-ELISA (Roche Diagnostics GmbH, Mannheim, Germany). We enrolled 43 hemodialysis patients (17 females; age 65.0 ± 12.7 years) and 23 controls (six females; age 62.1 ± 15.7 years). Between the two groups, there was no difference in telomere length (6.95 ± 3.25 vs. 7.31 ± 1.96 kb; P = 0.244) or in telomerase activity (1.82 ± 2.91 vs. 2.71 ± 3.0; P = 0.085). Telomere length correlated inversely with vintage of hemodialysis (r = -0.332, P = 0.030). In hemodialysis patients, positive telomerase activity correlated with telomere length (r = 0.443, P = 0.030). Only age, and neither telomere length nor telomerase activity, was an independent survival predictor (hazard ratio 1.116, 95% confidence interval 1.009-1.234, P = 0.033). In this study, telomere length and telomerase activity in PBMCs are not altered in hemodialysis patients compared with healthy controls. Long duration of hemodialysis treatment is associated with telomere shortening and positive telomerase activity with an increased telomere length in PBMCs of hemodialysis patients. The underlying mechanism and clinical implications of our findings require further investigation.

Patient-reported quality of life after primary major joint arthroplasty: a prospective comparison of hip and knee arthroplasty.

BACKGROUND: To investigate and compare the impact of primary hip (THA) and knee (TKA) arthroplasty on quality of life in patients with osteoarthritis, to determine patients' satisfaction with total joint arthroplasty, and to detect the effect of patients' demographic and clinical characteristics on outcome. METHODS: Three hundred seventy eight (378) patients with hip (174) and knee (204) osteoarthritis undergoing total joint arthroplasty (174 THA-204 TKA) were assessed pre- and post-operatively (6 weeks, 3, 6, and 12 months) using the Western Ontario and McMaster Osteoarthritis Index (WOMAC) and Centre for Epidemiological Studies Depression Scale (CES-D10). The patients' satisfaction with the results of total joint arthroplasty was also assessed. Differences were analyzed using general linear model for repeated measures. RESULTS: The one-year response rate was 97 % for THA and 90 % for TKA. WOMAC and CES-D10 scores improved significantly after one year for both THA and TKA (P < 0.0001). The improvement in WOMAC total score was significantly greater for TKA patients (P < 0.0001 at 12 months). WOMAC pain and stiffness improved earlier for THA (6 weeks), while TKA had equivalent improvements at 3 and 6 months respectively. Both THA/TKA displayed significant improvement of WOMAC function at 3 months but TKA had greater improvement. Age, body mass index, residence, education and social support were not significant predictors of quality of life after total joint arthroplasty. One year postoperatively 88 % of patients were satisfied. CONCLUSIONS: WOMAC and CES-D10 improved significantly one year postoperatively. Although pain and stiffness improved earlier in THA, functional improvement was inferior in THA compared to TKA.

Parental history of adenotonsillectomy is associated with obstructive sleep apnea severity in children with snoring.

OBJECTIVE: To test the hypothesis that history of adenoidectomy and/or tonsillectomy (AT) in at least 1 of the parents during childhood, is a risk factor for moderate-to-severe obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI] >5 episodes/hour) in the offspring with snoring. STUDY DESIGN: Data of children with snoring who were referred for polysomnography over 12 years by primary care physicians were reviewed. RESULTS: Data of 798 children without history of prior AT, neuromuscular, or genetic disorders or craniofacial abnormalities were analyzed. Of these children, 69.3% had tonsillar hypertrophy, 25.8% were obese, 26.8% had at least 1 parent with history of AT, and 22.1% had AHI >5 episodes/hour. Parental history of AT was significantly associated with moderate-to-severe OSA (logit model including sex, tonsillar hypertrophy, obesity, and physician-diagnosed wheezing; OR [95% CI], 1.70 [1.18-2.46]; P < .01). When significant variables from the logit model (tonsillar hypertrophy, obesity, parental history of AT) were considered independently or in combination, tonsillar hypertrophy combined with history of AT in at least 1 of the parents had high specificity (84.4%) and the highest positive likelihood ratio (1.78) for identifying children with AHI >5 episodes/hour. CONCLUSIONS: Among children with snoring who are referred for polysomnography by primary care physicians, those with tonsillar hypertrophy and parental history of AT have increased risk of moderate-to-severe OSA and represent 1 of the subgroups that should be prioritized for a sleep study in settings with limited resources.

Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm.

Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, p<0.001) levels. Adjustment for circadian BP rhythm status ascribed this finding exclusively to non-dippers (p<0.01). Two months after delivery, in 11 of the 21 non-dippers both circadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n=10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.