Surgical site infections increase the incidence of morbidity and mortality as well as health-care expenses. The cost of care increases threefold to fourfold as a consequence of surgical site ...infection after spinal surgery. The aim of the present study was to determine the role of subcutaneous fat thickness in the development of surgical site infection following cervical spine fusion surgery.
We performed a retrospective review of a consecutive cohort of 213 adult patients who underwent posterior cervical spine fusion between 2006 and 2008 at Duke University Medical Center. The horizontal distance from the lamina to the skin surface at the C5 level and the thickness of subcutaneous fat were measured, and the ratio of the fat thickness to the total distance at the surgical site was determined. Previously identified risk factors for the development of surgical site infection were also recorded.
Twenty-two of the 213 patients developed a postoperative infection. Obesity (body mass index ≥ 30 kg/m2) was not a significant risk factor for surgical site infection; the body mass index (and 95% confidence interval) was 29.4 ± 1.2 kg/m2 in the patients who developed a surgical site infection compared with 28.9 ± 0.94 kg/m2 in the patients without an infection. However, the thickness of subcutaneous fat and the ratio of the fat thickness to the lamina-to-skin distance were both significant risk factors for infection. The thickness of subcutaneous fat was 27.0 ± 2.5 mm in the patients who developed a surgical site infection group compared with 21.4 ± 0.88 mm in the patients without an infection (p = 0.042). The ratio of fat thickness to total thickness was 0.42 ± 0.019 in the patients who developed a surgical site infection compared with 0.35 ± 0.01 in the patients without an infection (p = 0.020). Multivariate analysis revealed this ratio to be an independent risk factor for developing a postoperative infection (odds ratio, 3.18; 95% confidence interval, 1.02 to 9.97).
The study demonstrated that the thickness of subcutaneous fat at the surgical site is a factor in the development of surgical site infection following cervical spine fusion and deserves assessment in the preoperative evaluation.
Globally, coral bleaching has been responsible for a significant decline in both coral cover and diversity over the past two decades. During the summer of 2010-11, anomalous large-scale ocean warming ...induced unprecedented levels of coral bleaching accompanied by substantial storminess across more than 12° of latitude and 1200 kilometers of coastline in Western Australia (WA).
Extreme La-Niña conditions caused extensive warming of waters and drove considerable storminess and cyclonic activity across WA from October 2010 to May 2011. Satellite-derived sea surface temperature measurements recorded anomalies of up to 5°C above long-term averages. Benthic surveys quantified the extent of bleaching at 10 locations across four regions from tropical to temperate waters. Bleaching was recorded in all locations across regions and ranged between 17% (±5.5) in the temperate Perth region, to 95% (±3.5) in the Exmouth Gulf of the tropical Ningaloo region. Coincident with high levels of bleaching, three cyclones passed in close proximity to study locations around the time of peak temperatures. Follow-up surveys revealed spatial heterogeneity in coral cover change with four of ten locations recording significant loss of coral cover. Relative decreases ranged between 22%-83.9% of total coral cover, with the greatest losses in the Exmouth Gulf.
The anomalous thermal stress of 2010-11 induced mass bleaching of corals along central and southern WA coral reefs. Significant coral bleaching was observed at multiple locations across the tropical-temperate divide spanning more than 1200 km of coastline. Resultant spatially patchy loss of coral cover under widespread and high levels of bleaching and cyclonic activity, suggests a degree of resilience for WA coral communities. However, the spatial extent of bleaching casts some doubt over hypotheses suggesting that future impacts to coral reefs under forecast warming regimes may in part be mitigated by southern thermal refugia.
Exercise has long-lasting benefits to bone health that may help prevent fractures by increasing bone mass, bone strength, and tissue quality. Long-term exercise of 6-12 weeks in rodents increases ...bone mass and bone strength. However, in growing mice, a short-term exercise program of 3 weeks can limit increases in bone mass and structural strength, compared to non-exercised controls. Short-term exercise can, however, increase tissue strength, suggesting that exercise may create competition for minerals that favors initially improving tissue-level properties over structural-level properties. It was therefore hypothesized that adding calcium and phosphorus supplements to the diet may prevent decreases in bone mass and structural strength during a short-term exercise program, while leading to greater bone mass and structural strength than exercise alone after a long-term exercise program. A short-term exercise experiment was done for 3 weeks, and a long-term exercise experiment was done for 8 weeks. For each experiment, male 16-week old C57BL/6 mice were assigned to 4 weight-matched groups-exercise and non-exercise groups fed a control or mineral-supplemented diet. Exercise consisted of treadmill running at 12 m/min, 30 min/day for 7 days/week. After 3 weeks, exercised mice fed the supplemented diet had significantly increased tibial tissue mineral content (TMC) and cross-sectional area over exercised mice fed the control diet. After 8 weeks, tibial TMC, cross-sectional area, yield force, and ultimate force were greater from the combined treatments than from either exercise or supplemented diet alone. Serum markers of bone formation (PINP) and resorption (CTX) were both decreased by exercise on day 2. In exercised mice, day 2 PINP was significantly positively correlated with day 2 serum Ca, a correlation that was weaker and negative in non-exercised mice. Increasing dietary mineral consumption during an exercise program increases bone mass after 3 weeks and increases structural strength after 8 weeks, making bones best able to resist fracture.
Down's syndrome is the most frequently identified cause of mental retardation, but information about mortality and comorbidity in people with Down's syndrome is limited.
We used data from US death ...certificates from 1983 to 1997 to calculate median age at death and standardised mortality odds ratios (SMORs) for common medical disorders in people with Down's syndrome.
Of 17 897 people reported to have Down's syndrome, median age at death increased from 25 years in 1983 to 49 years in 1997, an average increase of 1·7 years per year studied (p<0·0001). Median age at death was significantly lower in black people and people of other races than in white people with Down's syndrome. As expected, death certificates with a diagnosis of Down's syndrome were more likely to list congenital heart defects (SMOR 29·1, 95% CI 27·8–30·4), dementia (21·2, 19·6–22·7), hypothyroidism (20·3, 18·5–22·3), or leukaemia (1·6, 1·4–1·8) than were those that did not report Down's syndrome. By contrast, malignant neoplasms other than leukaemia were listed on death certificates of people with Down's syndrome less than one-tenth as often as expected (0·07, 0·06–0·08). A strikingly low SMOR for malignancy was associated with Down's syndrome at all ages, in both sexes, and for all common tumour types except leukaemia and testicular cancer.
Identification of factors responsible for the racial differences recorded could facilitate further improvement in survival of people with Down's syndrome. Reduced exposure to environmental factors that contribute to cancer risk, tumour-suppressor genes on chromosome 21, or a slower rate of replication or higher likelihood of apoptosis in Down's syndrome cells, could be possible reasons for paucity of cancer in people with Down's syndrome.
The tropical Atlantic interhemispheric gradient in sea surface temperature significantly influences the rainfall climate of the tropical Atlantic sector, including droughts over West Africa and ...Northeast Brazil. This gradient exhibits a secular trend from the beginning of the twentieth century until the 1980s, with stronger warming in the south relative to the north. This trend behavior is on top of a multidecadal variation associated with the Atlantic multidecadal oscillation. A similar long-term forced trend is found in a multimodel ensemble of forced twentieth-century climate simulations. Through examining the distribution of the trend slopes in the multimodel twentieth-century and preindustrial models, the authors conclude that the observed trend in the gradient is unlikely to arise purely from natural variations; this study suggests that at least half the observed trend is a forced response to twentieth-century climate forcings. Further analysis using twentieth-century single-forcing runs indicates that sulfate aerosol forcing is the predominant cause of the multimodel trend. The authors conclude that anthropogenic sulfate aerosol emissions, originating predominantly from the Northern Hemisphere, may have significantly altered the tropical Atlantic rainfall climate over the twentieth century.
The Raven-II is a platform for collaborative research on advances in surgical robotics. Seven universities have begun research using this platform. The Raven-II system has two 3-DOF spherical ...positioning mechanisms capable of attaching interchangeable four DOF instruments. The Raven-II software is based on open standards such as Linux and ROS to maximally facilitate software development. The mechanism is robust enough for repeated experiments and animal surgery experiments, but is not engineered to sufficient safety standards for human use. Mechanisms in place for interaction among the user community and dissemination of results include an electronic forum, an online software SVN repository, and meetings and workshops at major robotics conferences.
There are many clinical and histologic factors that are known to be valuable in predicting survival rates for patients with cutaneous malignant melanomas. Breslow thickness is considered to be the ...most reliable prognostic factor; however, thickness is a unidimensional measurement. A more accurate mensuration to predict biologic behavior might be one that takes into account the three-dimensional volume of the neoplasm. In a study of 35 primary malignant melanomas, the volumes of the dermal components of the tumors were calculated. Those patients with tumor volumes of 200 mm3 or less had a 91.4% 5-year disease-free survival rate, compared with survival rate of only 16.7% for those patients whose lesions had tumor volumes exceeding 200 mm3. On multivariate analysis, tumor volume exceeded thickness as a prognostic indicator. Thus, measurement of tumor volume proved to be of greater significance than thickness in predicting the outcome for patients with malignant melanomas.
Nonalcoholic fatty liver disease (NAFLD) and its progressive form non‐alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and ...indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long‐term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver‐related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long‐term outcomes, and patient‐reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies. Conclusion: Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. (Hepatology 2018;68:361‐371)
A newer generation of anti-cancer drugs targeting underlying somatic genetic driver events have resulted in high single-agent or single-pathway response rates in selected patients, but few patients ...achieve complete responses and a sizeable fraction of patients relapse within a year. Thus, there is a pressing need for identification of combinations of targeted agents which induce more complete responses and prevent disease progression. We describe the results of a combination screen of an unprecedented scale in mammalian cells performed using a collection of targeted, clinically tractable agents across a large panel of melanoma cell lines. We find that even the most synergistic drug pairs are effective only in a discrete number of cell lines, underlying a strong context dependency for synergy, with strong, widespread synergies often corresponding to non-specific or off-target drug effects such as multidrug resistance protein 1 (MDR1) transporter inhibition. We identified drugs sensitizing cell lines that are BRAFV600E mutant but intrinsically resistant to BRAF inhibitor PLX4720, including the vascular endothelial growth factor receptor/kinase insert domain receptor (VEGFR/KDR) and platelet derived growth factor receptor (PDGFR) family inhibitor cediranib. The combination of cediranib and PLX4720 induced apoptosis in vitro and tumor regression in animal models. This synergistic interaction is likely due to engagement of multiple receptor tyrosine kinases (RTKs), demonstrating the potential of drug- rather than gene-specific combination discovery approaches. Patients with elevated biopsy KDR expression showed decreased progression free survival in trials of mitogen-activated protein kinase (MAPK) kinase pathway inhibitors. Thus, high-throughput unbiased screening of targeted drug combinations, with appropriate library selection and mechanistic follow-up, can yield clinically-actionable drug combinations.
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