Validation of surgical site infection surveillance in orthopedic procedures

BACKGROUND: Valid data are essential for a national surveillance system of nosocomial infections. METHODS: In 8 hospitals conducting surgical site infection (SSI) surveillance for orthopedic procedures, a validation team performed a blinded retrospective chart review (10 operations with reported infections, 40 without) and interviewed infection control nurses. RESULTS: In total, 397 patient charts were reviewed. Positive and negative predictive values for routine surveillance were 94% (95% CI: 89%-99%) and 99% (95% CI: 99%-100%), respectively. When these results were applied to the aggregated surveillance data (403 infections, 10,068 noninfections), sensitivity was 75% (95% CI: 56%-93%) and specificity 100% (95% CI: 97%-100%). The following case finding methods were used: ward visits (in 7/8 hospitals), microbiology reports (5/8), ward notifications by link nurses (8/8), and other nursing (7/8) and medical (5/8) staff. The wound culture rate ranged from 9 to 67 per 1000 patient-days. All hospitals carried out postdischarge surveillance on readmission and all but 1 at follow-up visits and by an additional questionnaire. CONCLUSION: Most SSIs reported by the hospitals were true infections, showing that, when an SSI was reported, the definitions were correctly implemented. Some SSIs were missed, which might be due to weaknesses in case finding. Variation in diagnostic practices may also affect SSI rates.     

Physical activity, diet, and incident diabetes in relation to an ADRA2B polymorphism

PURPOSE: The 12Glu9 polymorphism of the alpha2B-adrenergic receptor gene may impair insulin secretion and modify the effects of a lifestyle intervention on the risk of type 2 diabetes, but the interaction with specific lifestyle components is unknown. We assessed the associations of leisure-time physical activity (LTPA), dietary changes, and weight loss on the risk of type 2 diabetes according to the 12Glu9 polymorphism in 481 participants of the Finnish Diabetes Prevention Study. METHODS AND RESULTS: The lifestyle intervention decreased the risk of diabetes in 9Glu carriers (9Glu9, intervention vs control, relative risk (RR) = 0.23, 95% confidence interval (CI) 0.09-0.62), but not in 12Glu12 homozygotes. In the combined intervention and control groups, increased total LTPA as estimated with a questionnaire decreased the risk of diabetes in 12Glu carriers (12Glu12, upper vs lower third, RR = 0.12, 95% CI 0.03-0.53) but not in 9Glu9 homozygotes (P for the interaction 0.033). In contrast, favorable dietary changes, estimated using a dietary score, reduced the risk of diabetes in those with the 9Glu9 genotype (upper vs lower third, RR = 0.21, 95% CI 0.06-0.75) but not in those with the 12Glu allele. Weight loss significantly decreased the risk of diabetes only in 12Glu carriers. CONCLUSION: Increased LTPA decreased the risk of type 2 diabetes more in those with the 12Glu allele of the ADRA2B gene, whereas dietary changes may have mediated the greater risk reduction of the lifestyle intervention in 9Glu homozygotes.     

Prenatal Origins of Poor Sleep in Children

Study Objectives:

We examined whether small body size at birth and prenatal tobacco or alcohol exposure predict poor sleep and more sleep disturbances in children.

Design:

An epidemiologic cohort study of 289 eight-year-old children born at term.

Measurements and results:

Sleep duration and efficiency were measured by actigraphy for 7 consecutive nights (mean = 7.1, SD = 1.2). We used both continuous measures of poor sleep and binary variables of short sleep and low sleep efficiency ( ≤ 10^th percentiles). Parents completed the Sleep Disturbance Scale for Children. Lower birth weight and shorter length at birth were associated with lower sleep efficiency. For every 1-SD decrease in weight and length at birth, the odds for low sleep efficiency increased by 1.7 fold (95% confidence interval [CI]: 1.1 to 2.7) and 2.2 fold (95% CI: 1.3 to 3.7), respectively. For every 1-SD decrease in ponderal index at birth, the risk of parent-reported sleep disorders increased by 1.4 fold (95% CI: 1.0 to 2.0). Moreover, children exposed prenatally to alcohol had a 2.9-fold (95% CI: 1.1 to 7.6) and 3.6-fold (95% CI: 1.3 to 10.0) increased risk for having short sleep and low sleep efficiency, respectively. The associations were not confounded by sex, gestational length, prenatal and perinatal complications, body mass index at 8 years, asthma, allergies, or parental socioeconomic status.

Conclusions:

Poor sleep in children may have prenatal origins. Possible mechanisms include alcohol consumption during pregnancy and other conditions associated with small body size at birth.

Citation:

Pesonen AK; Röaikköonen K; Matthews K; Heinonen K; Paavonen JE; Lahti J; Komsi N; Lemola S; Jöarvenpöaöa AL; Kajantie E; Strandberg T. Prenatal origins of poor sleep in children. SLEEP 2009;32(8):1086-1092.     

Matrilysin-1 (MMP-7) and MMP-19 are expressed by Paget's cells in extramammary Paget's disease

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant neoplasm of apocrine gland bearing skin characterized by intraepidermal proliferation of adenocarcinoma cells. Tumor growth depends on the ability of tumor cells to migrate by proteolysis and on angiogenesis. The matrix metalloproteinase (MMP) enzymes have been implicated in both of these processes in other types of skin cancer. METHODS: The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19 was analyzed by immuno- histochemistry and/or in situ hybridization in 27 EMPD and five mammary PD (MMPD) specimens. The distribution of laminin-5 (LN-5) and tenascin-C, two extracellular matrix proteins associated with tumor invasion, was studied by immunohistochemistry. RESULTS: MMP-7 (matrilysin-1) and MMP-19 were the most frequently expressed MMPs in Paget's cells. Overexpression of MMP-2, MMP-9, or MMP-13, which is seen in many cancers, was not evident in EMPD. LN-5 and tenascin-C positivity did not correlate with the level of invasion. MMP-7, MMP-13, and MMP-19 were detected abundantly in MMPD, while MMP-9 was absent. CONCLUSIONS: MMP expression did not generally associate with the level of invasion of EMPD. In three samples positive for MMP-7 and four samples positive for MMP-19, an underlying carcinoma was detected, suggesting the importance of these two MMPs as predictors of secondary EMPD or the putative origin of Paget's cells from the dermal adenocarcinoma cells of apocrine duct origin.     

Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis

Obesity is a risk factor for the development of many severe human diseases such as cardiovascular disorders, diabetes, and cancer, which are tightly linked to angiogenesis. The adipose tissue produces several growth factors/hormones including leptin, tumor necrosis factor alpha, and adiponectin. It has been found that adiponectin levels are reduced in obesity. Here, we report a unique function of adiponectin as a negative regulator of angiogenesis. In vitro, adiponectin potently inhibits endothelial cell proliferation and migration. In the chick chorioallantoic membrane and the mouse corneal angiogenesis assays, adiponectin remarkably prevents new blood vessel growth. Further, we demonstrate that the antiendothelial mechanisms involve activation of caspase-mediated endothelial cell apoptosis. Adiponectin induces a cascade activation of caspases-8, -9, and -3, which leads to cell death. In a mouse tumor model, adiponectin significantly inhibits primary tumor growth. Impaired tumor growth is associated with decreased neovascularization, leading to significantly increased tumor cell apoptosis. These data demonstrate induction of endothelial apoptosis as an unique mechanism of adiponectin-induced antiangiogenesis. Adiponectin, as a direct endogenous angiogenesis inhibitor, may have therapeutic implications in the treatment of angiogenesis-dependent diseases.     

Candidate susceptibility variants for esophageal squamous cell carcinoma

Esophageal cancer is common worldwide, and often fatal. The major histological subtype is esophageal squamous cell carcinoma (ESCC). ESCC shows familial aggregation and high heritability. Mutations in RHBDF2 cause tylosis, a very rare disorder characterized by high life‐time risk of ESCC, but no other well‐established predisposition genes have been identified. To identify candidate susceptibility variants for ESCC we utilized the Population Information System and the Finnish cancer registry to find study materials by clustering ESCC patients by family name at birth and municipality at birth. We collected archival tissue material and exome sequenced a total of 30 ESCC cases. We prioritized shared, deleterious and rare variants that were significantly enriched in our sample set compared to Finnish and population subset specific controls. Six variants passed filtering, the most frequent being a nonsense mutation in DNAH9 (p.Tyr1573Ter) found in four unrelated patients. DNAH9 has been reported to be frequently lost in ESCC tumors. In this study, one patient's tumor showed loss of the wild type allele of DNAH9 suggesting a tumor suppressive function. A missense variant in GKAP1 was shared by three patients, and missense variants in BAG1, NFX1, FUK, and DDOST by two each. EP300 which has previously been implicated in the genesis of ESCC had a missense variant segregating in three affected individuals in a single family. If validated in independent patient sets, these variants could serve as a tool towards prevention and early diagnosis of ESCC.