Tag Archives: GPCR Compound Library

Though meta analysis is ranked in the top of the

Though meta-analysis is ranked in the top of the evidence based medicine pyramid, some aspects of meta-analysis seem mysterious in nature. By definition, meta-analysis is a statistical method for combining the results of several independent studies addressing similar hypotheses in order to gain a better estimate of the effect size of an intervention.Meta coming from the Greek prefix “meta” means “after” or “beyond”. Thus, the idea is to pool the results of two studies or more in order to look beyond the primary results of the individual studies. The combined result can be evaluated as a secondary outcome using one of the size effect measures such as odds ratio, relative risk, and mean difference. In order to produce useful and meaningful results out of meta-analysis, a good systematic review should take place first. Systematic review is an integral part of any meta-analysis which started with an appropriate research question followed by a systematic retrieval of relevant studies through pre-planned inclusion and exclusion criteria. Summarizing the characteristics of the included studies concludes a systematic review. Subsequently, statistical analysis of the pooled results provides us with meta-analysis.
The number of published systematic reviews and meta-analyses in ophthalmic field has been increasing progressively over the past years. The number of publications increased from 3 per year in 1994 to almost 100 per year in 2010. This increased publication reflects the need for such design, especially with presence of several studies on the effect of an intervention or risk factor with varying directions or varying significance of outcome. Meta-analysis helps to interpret and clarify the direction and magnitude of the size effect. The major ophthalmic subspecialties that publish systematic reviews and meta-analyses are GPCR Compound Library which represents 35% of the publication of this type followed by glaucoma with publication rate of 21%.
In this journal issue, another retinal meta-analysis discusses the risk and contributing impact of a specific vascular endothelial growth factor (VEGF) polymorphism on retinopathy of prematurity (ROP). It has been known that the retinopathy of prematurity is a major cause of childhood blindness. In Saudi Arabia, retinopathy of prematurity was found to be comparable to reports from other parts of the world. In a cohort of premature infants with a mean gestational age of 28.4weeks, the incidence of ROP with birth weight of <1500 grams and <1250 grams was 41% and 50.7%, respectively. Nineteen of the 73 children with ROP (26%) reached threshold ROP, and needed laser treatment or cryotherapy. Development of ROP passes through two phases. In the first, the relative high oxygen inhibits the physiologically driven retinal vascularization by inhibiting the normal vascular endothelial growth factor (VEGF) secretion which is a hypoxia-inducible cytokine. In the second, there is relative hypoxia as a result of increased metabolic demand in the process of retinal maturation. Hypoxia promotes high-expression of VEGF and stimulates abnormal retinal vasculogenesis leading to the clinical manifestations of ROP such as neovascularization and proliferative retinopathy. Thus, VEGF is a key in normal and pathological retinal vascularization. Many researchers believe that single nucleotide polymorphisms (SNPs) of VEGF are related to the changes of protein expression during ROP and hence the susceptibility to develop ROP. However in case of the single nucleotide polymorphisms at positions rs 2010963, there are conflicting results concerning the direction of impact of VEGF polymorphism on ROP risk. Malik et al., in this issue, employed meta-analysis to show that VEGF-634G/C (rs 2010963) polymorphism may not be associated with ROP risk based on the pool results of six case-control studies including 355 cases and 471 controls. The pooled results of these studies in meta-analysis help to increase the sample size and improve the statistical power compared to the individual studies. The current study analyzed the association between VEGF-634G/C polymorphism and ROP risk using different models (dominant versus recessive) at different levels (allele versus ethnicity level) to provide more convincing result. The lack of GPCR Compound Library association between VEGF-634G/C polymorphism and ROP risk is in agreement with previous meta-analysis by Liu et al. who demonstrates that advanced ROP is not associated with VEGF gene –634G/C polymorphism.

Acute aortic dissection is a relatively

Acute aortic dissection is a relatively rare but life-threatening medical emergency, and can be extremely difficult to diagnose, especially when it presents atypically. The mortality rates are estimated at 50% by 48 hours and increase by 1% per hour if undiagnosed. The outcome is usually fatal with rapid development of serious complications. Clinical manifestations of acute aortic dissection are diverse in the general population. According to the previous report by Hagan et al only ∼ 72.7% of patients present with typical textbook presentations such as severe tearing chest pain. There is still a significant percentage of patients presenting with diverse atypical signs and symptoms which might mislead the first line physician to misdiagnose such a lethal condition.

Case Report
However, his urinalysis results were within the normal range, with no significant finding on kidney, ureter, and bladder (KUB) X-ray, nor was hydronephrosis found on renal ultrasound. Due to the unusual neurological presentation accompanied with the ureteral colic pain, vascular pathology was also suspected. Contrast enhanced thoracal and abdominal GPCR Compound Library CT was performed and revealed an extensive Stanford type A aortic dissection (Figure 1) involving whole aorta and bilateral common iliac arteries, with orifice of superior mesenteric artery (SMA) false lumen and a nearly 3.5 cm (in length) mural thrombosis in the left common iliac artery (Figure 2). The dissection was also extended to the left renal artery with regional cortical infarction at the inferior aspect of the left kidney (Figure 3). The patient was operated upon by the cardiovascular surgeons and had an uneventful postoperative course.

Discussion
Acute aortic dissection is missed in up to 38% of patients on initial evaluation, and in up to 28% of patients the diagnosis is made at autopsy. A 2011 report estimates an incidence of acute aortic dissection is three or four cases per 100,000 people per year. According to the International Registry of Acute Aortic Dissection (IRAD), the typical patient with acute aortic dissection is a male in his 70s with a history of hypertension, who presents with an abrupt onset of tearing, cutting, or shearing chest pain. GPCR Compound Library Several case series found that only ∼ 60–70% of patients present with typical manifestations. Absence of typical pain in patients with acute aortic dissection was noticed with a prevalence of 5–15% in Western populations.
In our case, the patient presented with some subtle unspecific symptoms such as left flank pain and left lower numbness, which had made the diagnosis very difficult and challenging for the emergency physician. The left flank pain that mimic ureteral colic pain is due to ischemia infarction of the left kidney, which is caused by the perfusion defect from left renal artery dissection. The ischemic pain of the kidney caused by vascular angina was devastating and often mistaken as renal colic by the patient. Along the ischemic change of the kidney which caused visceral pain that may elevate the vagal tone and cause the patient\’s bradycardia. The patient also complained of left lower limb numbness which was due to occlusion of the left common iliac artery by mural thrombosis from the extensive aortic dissection.
Classic presentations should not always be expected at the emergency room. Atypical presentation is not uncommon, but may cause a delay or misdiagnosis due to diverse subtle presentations. Ischemic necrosis due to ceased visceral circulation is one of the most severe complications of acute aortic dissection. A malperfusion syndrome occurs in 25–30% cases of acute aortic dissection and can dramatically reduce the chance of a successful outcome. Neurologic deficits have been associated with 18–30% of cases of acute aortic dissection. However, acute aortic dissection presenting with isolated ischemia of the leg is rare, occurring in ∼ 10% of patients, but it has been well described. Therefore, knowing the subtle and atypical presentations well and thinking beyond classic textbook descriptions are essential for emergency physicians in diagnosis of atypical acute aortic dissection.