Translational medicine and reliability of single-nucleotide polymorphism studies: can we believe in SNP reports or not?

BACKGROUND: The number of genetic association studies is increasing exponentially. Nonetheless, genetic association reports are prone to potential biases which may influence the reported outcome. AIM: We hypothesized that positive outcome for a determined polymorphism might be over-reported across genetic association studies analysing a small number of polymorphisms, when compared to studies analysing the same polymorphism together with a high number of other polymorphisms. METHODS: We systematically reviewed published reports on the association of glutathione s-transferase (GST) single-nucleotide polymorphisms (SNPs) and cancer outcome. RESULT: We identified 79 eligible trials. Most of the studies examined the GSTM1, theGSTP1 Ile105Val mutation, and GSTT1polymorphisms (n = 54, 57 and 46, respectively). Studies analysing one to three polymorphisms (n = 39) were significantly more likely to present positive outcomes, compared to studies examining more than 3 polymorphisms (n=40) p = 0.004; this was particularly evident for studies analysing the GSTM1polymorphism (p =0.001). We found no significant associations between journal impact factor, number of citations, and probability of publishing positive studies or studies with 1-3 polymorphisms examined. CONCLUSIONS: We propose a new subtype of publication bias in genetic association studies. Positive results for genetic association studies analysing a small number of polymorphisms (n = 1-3) should be evaluated extremely cautiously, because a very large number of such studies are inconclusive and statistically under-powered. Indeed, publication of misleading reports may affect harmfully medical decision-making and use of resources, both in clinical and pharmacological development setting.

Infections in patients with traumatic brain injury who undergo neurosurgery.

OBJECTIVE: Several factors place victims with traumatic brain injury (TBI) at increased risk for infection. The purpose of this study was to delineate the frequency, types and risk factors for infection in patients with TBI who undergo neurosurgery. MATERIALS AND METHODS: Retrospective surveillance of infections in patients with TBI, aged  ≥18 years who underwent neurosurgery in University of Crete between 1999 and 2005. RESULTS: Two hundred fifty-eight patients (76.7% men) who underwent 342 procedures were included. One hundred forty-two infections occurred, mainly lower respiratory tract infections (44.4% of the number of infections) and surgical site infections (SSIs) (25.4%). In multivariate analysis, SSIs were independently associated with the length of stay (p < 0.001), history of malignancy (p = 0.008), CSF leak (p = 0.012), any concomitant infection (p = 0.010), particularly urinary tract infections (p = 0.001) and the use of lumbar and/or ventricular drains (p = 0.005). Meningitis was independently associated with the total length of stay (p < 0.001), the need for intubation and mechanical ventilation beyond surgery (p = 0.028) and the presence of a lumbar and/or ventricular drain (p < 0.001). CONCLUSIONS: Respiratory tract infections were common in patients with TBI who underwent surgery with Acinetobacter spp. being the emerging offending pathogens. Device-related postoperative communication of the CSF and the environment was a significant risk factor for SSI development and meningitis in particular. Malignancy was an independent risk factor for SSIs. The prevalence of the offending pathogens must be determined institution by institution for the establishment of proper antibiotic treatment on suspicion.

A 66-year-old male with lower abdominal lump: an unusual presentation of an uncommon abdominal pathology.

A 66-year-old Caucasian male was admitted following symptoms of intermittent umbilical pain aggravated after meals and associated with vomiting of contents. Physical examination revealed a tender, partially reducible swelling suspicious of complicated umbilical hernia. Abdominal x-ray revealed dilated small bowel loops which appeared consistent with clinical diagnosis. He underwent a laparotomy subsequently which revealed a small defect in the linea alba with viable small bowel and two firm mesenteric masses encroaching the lumen approximately two feet from the ileocaecal junction. The histology of the excised bowel and masses revealed that the tumour composed of bland spindle cells with slender to plump nuclei and eosinophilic cytoplasm. Mesenteric fibromatosis are the most common primary tumours of the mesentery and constitute about 3.5% of all fibrous tissue tumours. Intra-abdominal desmoids are very rare and benign tumours but are very aggressive and should be considered in the differential diagnosis of acute abdominal pain.