Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 2000 were followed up for an average of 6.2 years, during which 1,833 CRC cases were observed. Detailed information on consumption of alcoholic beverages at baseline (all cases) and during lifetime (1,447 CRC cases, 69% of the cohort) was collected from questionnaires. Cox proportional hazard models were used to examine the alcohol-CRC association. After adjustment for potential confounding factors, lifetime alcohol intake was significantly positively associated to CRC risk (hazard ratio, HR=1.08, 95%CI=1.04-1.12 for 15 g/day increase), with higher cancer risks observed in the rectum (HR=1.12, 95%CI=1.06-1.18) than distal colon (HR=1.08, 95%CI=1.01-1.16), and proximal colon (HR=1.02, 95%CI=0.92-1.12). Similar results were observed for baseline alcohol intake. When assessed by alcoholic beverages at baseline, the CRC risk for beer (HR=1.38, 95%CI=1.08-1.77 for 20-39.9 vs. 0.1-2.9 g/day) was higher than wine (HR=1.21, 95%CI=1.02-1.44), although the two risk estimates were not significantly different from each other. Higher HRs for baseline alcohol were observed for low levels of folate intake (1.13, 95%CI=1.06-1.20 for 15 g/day increase) compared to high folate intake (1.03, 95%CI=0.98-1.09). In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day.     

Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors.

PURPOSE: Osteonecrosis of the jaw (ONJ) has been associated recently with the use of pamidronate and zoledronic acid. We studied the incidence, characteristics, and risk factors for the development of ONJ among patients treated with bisphosphonates for bone metastases. PATIENTS AND METHODS: ONJ was assessed prospectively since July 2003. The first bisphosphonate treatment among patients with ONJ was administered in 1997. Two hundred fifty-two patients who received bisphosphonates since January 1997 were included in this analysis. RESULTS: Seventeen patients (6.7%) developed ONJ: 11 of 111 (9.9%) with multiple myeloma, two of 70 (2.9%) with breast cancer, three of 46 (6.5%) with prostate cancer, and one of 25 (4%) with other neoplasms (P = .289). The median number of treatment cycles and time of exposure to bisphosphonates were 35 infusions and 39.3 months for patients with ONJ compared with 15 infusions (P < .001) and 19 months (P = .001), respectively, for patients with no ONJ. The incidence of ONJ increased with time to exposure from 1.5% among patients treated for 4 to 12 months to 7.7% for treatment of 37 to 48 months. The cumulative hazard was significantly higher with zoledronic acid compared with pamidronate alone or pamidronate and zoledronic acid sequentially (P < .001). All but two patients with ONJ had a history of dental procedures within the last year or use of dentures. CONCLUSION: The use of bisphosphonates seems to be associated with the development of ONJ. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor.     

Whole-blood interferon-gamma assay for the diagnosis of tuberculosis infection in an unselected Greek population

Background and objective:   Although QuantiFERON-TB Gold (QFT-G) has been approved for the diagnosis of latent tuberculosis infection (LTBI), there are limited data regarding its performance in routine clinical practice. The aim of this study was to compare QFT-G 'In Tube' results, based on stimulation with Mycobacterium tuberculosis- specific antigens, with tuberculin skin test (TST) results in an unselected hospital-based Greek population.
Methods:   This was a prospective study of inpatients and outpatients in the University Hospital of Larissa, Greece. Demographic, clinical and microbiological data were collected and correlated to the QFT-G 'In Tube' results. Agreement was tested using the Q -test; kappa coefficient and confounding factors were adjusted for by univariate and multivariable logistic regression.
Results:   Among the 191 patients with valid results for both tests, the concordance between the TST and the QFT-G was 68.5%, with a kappa value of 0.38 (95% CI 0.2–0.5). In 27 (14.1%) patients with active tuberculosis, QFT-G 'In Tube' yielded 85.1% positive results compared with 74% for the TST ( P  = 0.45).
Conclusions:   Overall agreement between the QFT-G 'In Tube' assay and the TST in this unselected hospital population was low, mainly due to discordant TST-positive/QFT-negative results.     

How trust affects performance of interprofessional health-care teams.

ABSTRACT

Interprofessional teamwork in health-care settings is considered a valuable means of enhancing patient management. Literature has highlighted the importance of trust in building effective health-care teams. The present study aimed to investigate and further understand the perceptions of health-care professionals regarding trust and performance within their working team, as well as to assess the association between them and team performance. “TRUST” questionnaire, a valid instrument for measuring the relationship of trust and team performance was distributed to the members of the perioperative teams located in two different hospitals (a University and a General Hospital) in Greece. Two multivariate linear regression models were developed to reveal the significant predictors of high performance per hospital. Among the major findings revealed were 1) trust and performance were closely related 2) slight yet significant variations were observed between the University and the General Hospital and 3) trust level, years of previous experience and number of team members were among the key predictors of effective team performance. This study conveys new knowledge on trust and performance within health-care settings with limited resources and is expected to guide future interventions aiming to enhance team performance.     

Intraoperative real-time fluorescence angiography with indocyanine green for evaluation of intestinal viability during surgery for an incarcerated obturator hernia: a case report

Background

Bowel incarceration represents a dreaded complication amongst patients with hernias. The intraoperative evaluation of the bowel perfusion following hernia reduction with regard to the need for resection of ischaemic bowel can be challenging. In this case report we discuss intraoperative fluorescence angiography with indocyanine green (ICG) as an objective means of accessing bowel perfusion following hernia reduction.

Case presentation

The case of a 92-year-old, caucasian, female patient presenting with symptoms of small bowel obstruction secondary to an incarcerated left sided obturator hernia is presented. An incarcerated segment of the small bowel was reduced during emergency laparoscopy. Intraoperative ICG fluorescence angiography revealed ischaemic changes in the normal appearing bowel, so that the involved segment was resected. The postoperative course was uneventful and the patient was discharged home safely on postoperative day seven.

Conclusion

Intraoperative ICG fluorescence angiography provides an objective method of judging bowel perfusion and therefore represents a useful tool for assessing intestinal perfusion in patients with incarcerated hernia.

     

Greek centenarians: assessment of functional health status and life-style characteristics

Centenarians represent an intriguing model for ageing studies, since they demonstrate extreme longevity by definition, and at the same time a proportion of them have aged successfully. Here, we present data from the first nationwide study on Greek centenarians concerning their functional health status and life-style characteristics. We have identified 489 individuals (77% women) born in 1900 or before who were still alive between the years 2000 and 2002. Socio-demographic characteristics, activities of daily living (ADLs), living conditions, dependence on other people, former and current diseases and health disorders, current medication, nutrition and personal habits were recorded for every subject. Interestingly, only 2% of Greek centenarians lived in nursing homes, while the majority lived with their family or relatives. Furthermore, 6% were free from severe health disorders, autonomous (based on simple criteria for ADLs) and also leading an active social life, and hence may be considered as being in optimal condition. This group of centenarians may serve as a valuable source of information on genetic, environmental, and psychosocial determinants of successful ageing.     

Management of an extrasphincteric fistula in an HIV-positive patient by using fibrin glue: a case report with tips and tricks

Background  

Individuals with impaired immunity are at higher risk of perianal diseases. Concerning complex anal fistulas impaired healing and complication rates are also higher. Definitive treatment of a fistula aims controlling the purulent discharge and prevents its recurrence. It depends mainly on the trajectory of the fistula and the underlying disease.     

Acute West Nile virus neuroinvasive infections: cross-reactivity with dengue virus and tick-borne encephalitis virus

Cross-reactions in serology are common among flaviviruses. During the outbreak of West Nile virus (WNV) infections in Greece in 2010, WNV IgM-positive serum and cerebrospinal fluid samples were tested for the presence of IgM and IgG antibodies against Dengue virus (DENV) and tick-borne encephalitis virus. Higher cross-reactivity was observed in IgM antibodies between WNV and DENV; however, the index of the WNV antibodies was in all cases higher than that of the DENV antibodies. There is a need for caution when evaluating serologic results of flaviviral infections, while efforts have to be focused on the development of diagnostic assays with increased specificity.     

Endogenous angiogenesis inhibitor blocks tumor growth via direct and indirect effects on tumor microenvironment

Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) belongs to a small family of endogenous proteins that inhibits a group of enzymes, the matrix metalloproteinases (MMPs). TIMP-2 inhibits endothelial cell proliferation and migration in vitro and angiogenesis in vivo, through MMP-dependent and -independent mechanisms. However, little is known regarding the contribution of these mechanisms to the antitumor effects of TIMP-2. Using a retroviral delivery system, we stably overexpressed TIMP-2 and its mutant Ala+TIMP-2 (devoid of MMP inhibitory activity) in human adenocarcinoma A549 cells. Using real time PCR, and enzyme-linked immunosorbent assay (ELISA), we confirmed enhanced TIMP-2 expression and its MMP inhibitory activity by reverse zymography. In vitro, growth assays suggested that TIMP-2 and Ala+TIMP-2 did not alter basal cell proliferation rates, however, tumor cell migration and invasion were inhibited. In vivo, both TIMP-2 and Ala+TIMP-2 A549 xenografts exhibited reduced growth rate, CD31 immunostaining indicated decreased intratumoral microvascular density, and TUNEL demonstrated enhanced tumor cell apoptosis. Immunoblotting and immunohistochemical analyses of A549 xenograft tissues with either phospho-FAK (Tyr397) or phospho-AKT (Ser473) showed decreased activation in both TIMP-2 and Ala+TIMP-2 tumor cells. We conclude that TIMP-2-mediated inhibition of tumor growth occurs, at least in part, independently of MMP inhibition, and is a consequence of both direct effects of TIMP-2 on tumor cells and modulation of the tumor microenvironment.     

Efficiency of translation termination in humans is highly dependent upon nucleotides in the neighbourhood of a (premature) termination codon

BACKGROUND: Spontaneous read-through of a premature termination codon (PTC) has so far not been observed in patients carrying nonsense mutations. This report describes a patient with junctional epidermolysis bullosa who was expected to die because of compound heterozygous nonsense mutations in the gene LAMA3 (R943X/R1159X), but was rescued by spontaneous read-through of the R943X allele. RESULTS AND CONCLUSION: FACS analysis of cells carrying various PTCs surrounded by their natural neighbouring codons revealed significant reporter gene expression despite the PTC only for this patient's genetic context. Gene expression could be abolished by replacing the first or third nucleotide before, or one of the two nucleotides following the PTC. Site-directed mutagenesis was used to identify genotypes allowing PTC read-through. The genetic context of the LAMA3 mutation R943X is close to a hypothetical consensus sequence for maximum PTC read-through. Bioinformatic analysis showed that this consensus sequence is present in four sequences from the NCBI reference database, each of which contains another in-frame termination codon three or four codons apart. This indicates strong selective pressure against leaky termination codons in the human genome. This patient's mutated full length mRNA escaped nonsense-mediated decay, leading to LAMA3 mRNA levels similar to those of a healthy control, and full length laminin α3 could be detected in culture supernatant of the patient's keratinocytes. Immunofluorescence analyses of skin biopsies and continuous clinical improvement of the patient's condition suggested accumulation of intact laminin-332 in the epidermal basement membrane. These findings provide important clues for the prediction of PTC read-through in human genetic disease.