Theodoros N. Sergentanis

Mediterranean diet, stroke, cognitive impairment, and depression: A meta‐analysis

This meta‐analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease.

Safety and Efficacy of Ultrasound-Enhanced Thrombolysis A Comprehensive Review and Meta-Analysis of Randomized and Nonrandomized Studies

Background and Purpose— Ultrasound-enhanced thrombolysis is a promising new approach to facilitate reperfusion therapies for acute ischemic stroke. So far, 3 different ultrasound technologies were used to increase the thrombolytic activity of tissue plasminogen activator (tPA), including transcranial Doppler (TCD), transcranial color-coded duplex (TCCD), and low-frequency ultrasound. We performed a meta-analysis to evaluate the safety and efficacy of ultrasound-enhanced thrombolysis compared to the current standard of care (intravenous tPA). Subjects and Methods— Through Medline, Embase, and Cochrane database search, we identified and abstracted all studies of ultrasound-enhanced thrombolysis in acute cerebral ischemia. Principal investigators were contacted if data not available through peer-reviewed publication were needed. Symptomatic intracerebral hemorrhage (sICH) and recanalization rates were compared between tPA, tPA+TCD±microspheres (&mgr;S), tPA+TCCD±&mgr;S, and tPA+low-frequency ultrasound. Results— A total of 6 randomized (n=224) and 3 nonrandomized (n=192) studies were identified. The rates of symptomatic intracerebral hemorrhage in randomized studies were as follows: tPA+TCD, 3.8% (95% CI, 0%–11.2%); tPA+TCCD, 11.1% (95% CI, 0%–28.9%); tPA+low-frequency ultrasound, 35.7% (95% CI, 16.2%– 61.4%); and tPA alone, 2.9% (95% CI, 0%–8.4%). Complete recanalization rates were higher in patients receiving combination of TCD with tPA 37.2% (95% CI, 26.5%– 47.9%) compared with patients treated with tPA alone 17.2% (95% CI, 9.5%–24.9%). In 8 trials of high-frequency (TCD/TCCD) ultrasound-enhanced thrombolysis, tPA+TCD/TCCD±&mgr;S was associated with a higher likelihood of complete recanalization (pooled OR, 2.99; 95% CI, 1.70–5.25; P=0.0001) when compared to tPA alone. High-frequency ultrasound-enhanced thrombolysis was not associated with an increased risk of symptomatic intracerebral hemorrhage (pooled OR, 1.26; 95% CI, 0.44–3.60; P=0.67). Conclusions— The present safety and signal-of-efficacy data of high-frequency ultrasound-enhanced thrombolysis should be taken into account in the design of future randomized controlled trials.

Carotid Artery Stenting Versus Carotid Endarterectomy A Comprehensive Meta-Analysis of Short-Term and Long-Term Outcomes

Background and Purpose— The comparison between carotid endarterectomy and carotid artery stenting (CAS) remains a debated field, especially in the context of long-term outcomes. Methods— Concerning the short-term (30-day) analysis, the numbers of outcomes per arm were abstracted, whereas outcomes per arm and hazard ratios were abstracted for long-term (≥1-year) results. Results— Thirteen randomized trials (3723 carotid endarterectomy and 3754 CAS patients) were eligible. Regarding short-term outcomes, CAS was associated with elevated risk for stroke and “death or stroke.” CAS also exhibited a marginal trend toward higher death and “death or disabling stroke” rates. Carotid endarterectomy presented with higher rates of myocardial infarction and cranial nerve injury. Concerning long-term outcomes, CAS was associated with higher rates of stroke (pooled OR, 1.37; 95% CI, 1.13 to 1.65) and “death or stroke” (pooled OR, 1.25; 95% CI, 1.06 to 1.48). These findings were replicated at the level of pooled hazard ratios and marginally regarding secondary preventive efficacy. The difference in long-term stroke rates was particularly sizeable in patients >68 years, but little difference in rates was observed in those <68 years. No statistically significant heterogeneity became evident. Metaregression did not reveal any significant modifying effect mediated by symptomatic/asymptomatic status, distal protection, early termination of trials, area of study origin, or CAS learning curve. Conclusions— This meta-analysis points to the significantly less frequent stroke events after carotid endarterectomy at the long-term context. The outcomes of carotid endarterectomy seem superior to CAS, but there may be subgroups, particularly younger patients, in whom the results seem equivalent.

GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: A comprehensive meta-analysis

Glutathione S-transferases (GSTs) catalyse reactions between glutathione and lipophilic compounds with electrophilic centres, leading to neutralisation of toxic compounds, xenobiotics and products of oxidative stress. Controversy exists about whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, GSTP1 Ile105Val and GSTA1 *A/*B) represent risk factors for colorectal cancer. This meta-analysis aims to examine the associations between the above-mentioned polymorphisms and colorectal cancer risk. Forty-four studies were eligible for GSTM1 (11,998 colorectal cancer cases, 17,552 controls), 34 studies for GSTT1 (8596 cases, 13,589 controls), 19 studies for GSTP1 (5421 cases, 7671 controls) and four studies for GSTA1 polymorphism (1648 cases, 2039 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Separate analyses were conducted on Caucasian and Chinese populations. Where appropriate, sensitivity analysis concerning the deviation of genotype frequencies in controls from the Hardy-Weinberg equilibrium was performed. GSTM1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR=1.150, 95% confidence interval (CI): 1.060-1.248, random effects); no significant association was detected for Chinese subjects (pooled OR=1.025, 95% CI: 0.903-1.163, fixed effects). Similarly, GSTT1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR=1.312, 95% CI: 1.119-1.538, random effects); the association in Chinese subjects was not significant (pooled OR=1.068, 95% CI: 0.788-1.449, random effects). Concerning GSTP1 Ile105Val no significant associations were demonstrated in either race. GSTA1 *A/*B polymorphism was not associated with colorectal cancer risk. GSTM1 and GSTT1 null genotypes confer additional risk for colorectal cancer in Caucasian populations.

Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer—a systematic review and meta-analysis

BACKGROUND In response to the ongoing debate on the long-term effects of assisted reproduction technologies, such as IVF, we systematically reviewed and meta-analyzed available evidence on the association between controlled ovarian hyperstimulation for IVF and risk of ovarian, endometrial and cervical cancer. METHODS Eligible studies were identified and pooled effect estimates for relative risk (RR) were calculated by cancer type among two reference groups (general population or infertile women), through fixed- or random-effects models as appropriate. RESULTS Nine cohort studies were synthesized, corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were studied. The synthesis of studies with general population as the reference group pointed to a statistically significant positive association between IVF and increased risk for ovarian (RR = 1.50, 95% confidence interval (CI): 1.17-1.92) and endometrial (RR = 2.04, 95% CI: 1.22-3.43), but not cervical (RR = 0.86, 95% CI: 0.49-1.49) cancers. On the contrary, when infertile women were used as the reference group, no significant associations with ovarian, endometrial or cervical cancer types were noted (RR = 1.26, 95% CI: 0.62-2.55 RR = 0.45, 95% CI: 0.18-1.14 and RR = 5.70, 95% CI: 0.28-117.20, respectively). CONCLUSIONS IVF does not seem to be associated with elevated cervical cancer risk, nor with ovarian or endometrial cancer when the confounding effect of infertility was neutralized in studies allowing such comparisons. Of note, only one study provided follow-up longer than 10 years for the group exposed to IVF. Future cohort studies should preferably use infertile women as the reference group, rely on IVF-registered valid exposure data, adjust for a variety of meaningful confounders and adopt relatively longer follow-up periods before sound conclusions are drawn.

Obesity and risk of malignant melanoma: A meta-analysis of cohort and case–control studies

Although obesity is an established risk factor for several cancer types, its possible role in the aetiology of malignant melanoma remains unclear. This meta-analysis aims to examine the association between obesity and melanoma risk, exploring any tentative gender-specific associations. After the identification of eligible studies, we estimated pooled effect estimates (odds ratios and relative risks), undertook a meta-regression analysis and analysed separately risk of malignant melanoma among males and females in relation to body mass index (BMI) and body surface area (BSA). Out of the 21 eligible articles, 11 used a case-control design encompassing 4460 cases/6342 controls; 10 used a cohort design whose total size comprised 7895 incident cases/6,368,671 subjects. Among males, the pooled effect estimate was 1.31 (95%confidence interval (CI): 1.18-1.45) for overweight and 1.31 (95%CI: 1.19-1.44) for obese. Meta-regression revealed no significant slope, most probably due to the underlying plateau in effect estimates. Among females, no significant association was documented; the pooled effect estimate for overweight and obese subjects was 0.98 (95%CI: 0.92-1.05) and 0.99 (95%CI: 0.83-1.18), respectively. Noticeably, there was evidence for confounding between sunlight exposure and obesity in females. All results were reproducible upon analyses on BSA. In conclusion, overweight and obesity are associated with increased risk of malignant melanoma among males. Meticulous assessment of sunlight exposure is needed especially in women, since self limited public sun exposure may be prevalent among overweight or obese females. Higher-order associations between BMI and melanoma risk should be addressed and examined by the future studies.

Risk factors for intraoperative floppy iris syndrome: a meta-analysis.

PURPOSE To evaluate risk factors (hypertension, diabetes mellitus, and current tamsulosin, alfuzosin, terazosin, or doxazosin use) for intraoperative floppy iris syndrome (IFIS) in patients undergoing phacoemulsification cataract surgery. DESIGN Systematic review and meta-analysis of the literature. PARTICIPANTS Seventeen eligible studies (17 588 eyes) examining the association between IFIS and risk factors. METHODS Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened. Language restrictions were not used, and data were extracted from each eligible study by 2 investigators working independently. For medications, 2 separate analyses were performed: an analysis using a dichotomous criterion (use/non-use of the examined agent) and an alternative analysis performing comparisons with patients not receiving any α(1)-blocker. The fixed-effects model (Mantel-Haenszel method) or the random-effects (DerSimonian Laird) model was appropriately used to calculate the pooled odds ratio (OR). Publication bias was appropriately assessed. MAIN OUTCOME MEASURES Pooled OR for the incidence of IFIS. RESULTS The pooled OR for IFIS after tamsulosin use was approximately 40-fold greater (or 16.5 at the alternative analysis) than that after alfuzosin use, that is, the second α(1)-blocker in order of effect size. Alfuzosin and terazosin were also associated with IFIS with comparable ORs; the effect of doxazosin reached formal statistical significance at the alternative analysis. Intraoperative floppy iris syndrome was positively associated with hypertension (pooled OR = 2.2, 95% confidence interval [CI], 1.2-4.2, fixed effects) but not with diabetes mellitus (pooled OR = 1.3, 95% CI, 0.7-2.2, fixed effects). CONCLUSIONS This meta-analysis has highlighted a hierarchy concerning the role of α(1)-blockers in IFIS, indicating an extremely sizeable effect size of tamsulosin; this may entail important physiologic implications. Alfuzosin, terazosin, and doxazosin presented with comparable effect sizes. Hypertension, but not diabetes mellitus, emerged as a risk factor for IFIS.

Nasal continuous positive airway pressure (nCPAP) treatment for obstructive sleep apnea, road traffic accidents and driving simulator performance: A meta-analysis

We used meta-analysis to synthesize current evidence regarding the effect of nasal continuous positive airway pressure (nCPAP) on road traffic accidents in patients with obstructive sleep apnea (OSA) as well as on their performance in driving simulator. The primary outcomes were real accidents, near miss accidents, and accident-related events in the driving simulator. Pooled odds ratios (ORs), incidence rate ratios (IRRs) and standardized mean differences (SMDs) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity. Furthermore, risk differences (RDs) and numbers needed to treat (NNTs) were estimated for real and near miss accidents. Meta-regression analysis was performed to examine the effect of moderator variables and publication bias was also evaluated. Ten studies on real accidents (1221 patients), five studies on near miss accidents (769 patients) and six studies on the performance in driving simulator (110 patients) were included. A statistically significant reduction in real accidents (OR=0.21, 95% CI=0.12-0.35, random effects model; IRR=0.45, 95% CI=0.34-0.59, fixed effects model) and near miss accidents (OR=0.09, 95% CI=0.04-0.21, random effects model; IRR=0.23, 95% CI=0.08-0.67, random effects model) was observed. Likewise, a significant reduction in accident-related events was observed in the driving simulator (SMD=-1.20, 95% CI=-1.75 to -0.64, random effects). The RD for real accidents was -0.22 (95% CI=-0.32 to -0.13, random effects), with NNT equal to five patients (95% CI=3-8), whereas for near miss accidents the RD was -0.47 (95% CI=-0.69 to -0.25, random effects), with NNT equal to two patients (95% CI=1-4). For near miss accidents, meta-regression analysis suggested that nCPAP seemed more effective among patients entering the studies with higher baseline accident rates. In conclusion, all three meta-analyses demonstrated a sizeable protective effect of nCPAP on road traffic accidents, both in real life and virtual environment.

In vitro fertilization and risk of childhood leukemia in Greece and Sweden.

Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets.

Efficacy and safety of laparoscopic mini gastric bypass. A systematic review

BACKGROUND Laparoscopic mini-gastric bypass (LMGB) is a relatively new bariatric procedure; published studies are accumulating in various settings. The objective of this study was to summarize the available evidence about the efficacy and safety of LMGB. METHODS A systematic search in the literature was performed , and PubMed and reference lists were scrutinized (end-of-search date: July 15, 2013). For the assessment of the eligible articles, the Newcastle-Ottawa quality assessment scale was used. RESULTS Ten eligible studies were included in this study, reporting data on 4,899 patients. According to all included studies, LMGB induced substantial weight and body mass index reduction, as well as substantial excess weight loss. Moreover, resolution or improvement in all major associated medical illnesses and improvement in overall Gastrointestinal Quality of Life Index score were recorded. Major bleeding and anastomotic ulcer were the most commonly reported complications. Readmission rate ranged from 0%- 11%, whereas the rate of revision operations ranged from .3%- 6%. The latter were conducted due to a variety of medical reasons such as inadequate or excessive weight loss, malnutrition, and upper gastrointestinal bleeding. Finally, the mortality rate ranged between 0% and .5% among primary LMGB procedures. CONCLUSION LMGB represents an effective bariatric procedure; its safety and minimal postoperative morbidity seem remarkable. Randomized comparative studies seem mandatory for the further evaluation of LMGB.