Nosocomial or not? A combined epidemiological and genomic investigation to understand hospital-acquired COVID-19 infection on an elderly care ward.

BACKGROUND: COVID-19 has the potential to cause outbreaks in hospitals. Given the comorbid and elderly cohort of patients hospitalized, hospital-acquired COVID-19 infection is often fatal. Pathogen genome sequencing is becoming increasingly important in infection prevention and control (IPC). AIM: To inform the understanding of in-hospital SARS-CoV-2 transmission in order to improve IPC practices and to inform the future development of virological testing for IPC. METHODS: Patients detected COVID-19 positive by polymerase chain reaction on Ward A in April and May 2020 were included with contact tracing to identify other potential cases. Genome sequencing was undertaken for a subgroup of cases. Epidemiological, genomic, and cluster analyses were performed to describe the epidemiology and to identify factors contributing to the outbreak. FINDINGS: Fourteen cases were identified on Ward A. Contact tracing identified 16 further patient cases; in addition, eight healthcare workers (HCWs) were identified as being COVID-19 positive through a round of asymptomatic testing. Genome sequencing of 16 of these cases identified viral genomes differing by two single nucleotide polymorphisms or fewer, with further cluster analysis identifying two groups of infection (a five-person group and a six-person group). CONCLUSION: Despite the temporal relationship of cases, genome sequencing identified that not all cases shared transmission events. However, 11 samples were found to be closely related and these likely represented in-hospital transmission. This included three HCWs, thereby confirming transmission between patients and HCWs.

Comparing the efficacy of three techniques to reduce isoagglutinin titers in AB0 incompatible kidney transplant recipients.

ABO incompatible (ABOi) organ transplantation requires pre-transplant reduction of the recipient's IgG and IgM isoagglutinin titer against the donor to prevent hyperacute rejection. Over the past four years we primarily used unspecific IgG immunoadsorption (IA) for this purpose and combined this selectively with membrane filtration (IAc) to reduce IgM isoagglutinines. In patients with an initial IgG titer against donor below 1:64, plasma exchange (PE) was initiated. In this retrospective analysis covering January 2012 to August 2015 we compared how efficiently IgG and IgM isoagglutinines in a total of 22 ABOi kidney transplant recipients were reduced by either IA (n = 75 sessions), IAc (n = 14 sessions) or PE (n = 40 sessions). Median pre-treatment IgG isoagglutinin titers were 32 (4-4096) while IgM titers were 16 (1-256) respectively. Mean IgG reduction by either treatment modality was 1.3 ± 0.9 (IA), 1.8 ± 1.0 (IAc) and 2.6 ± 1.3 (PE) titer steps per session (p < 0.001 IA vs. PE; p < 0.04 PE vs. IAc). Mean IgM reduction was 0.6 ± 0.6 (IA), 1.8 ± 0.8 (IAc) and 2.4 ± 1.9 (PE) titer steps (p < 0.001 for both IA vs. PE and IA vs. IAc). Our data indicate that PE efficiently removed IgG- and IgM isoagglutinines. By processing only half the plasma volume per treatment PE was twice as effective as IA in terms of IgG-type isoagglutinin removal in our patient group. This is best explained by the presence of soluble AB0 antigens in the FFP used as plasma replacement. These advantages in efficacy have to be weighed against the potential hazards of PE. Combination of IA and plasma filtration effectively removes IgM-type and even enhances net IgG-type isoagglutinin elimination compared to IA alone. When trying to avoid PE, combined application of IA and IAc is a possible and effective way to reduce isoagglutinin titers before ABOi transplantation.

A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3.

PURPOSE: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and Candida skin test reagent as a novel adjuvant. PATIENTS AND METHODS: The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 µg per peptide). RESULTS: The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 µg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations (P = 0.02). CONCLUSION: This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests that Candida, which induces interleukin-12 (IL-12) in vitro, may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted.

Mesenteric lymphatic vessels adapt to mesenteric venous hypertension by becoming weaker pumps.

Lymphangions, the segments of lymphatic vessels between two adjacent lymphatic valves, actively pump lymph. Acute changes in transmural pressure and lymph flow have profound effects on lymphatic pump function in vitro. Chronic changes in pressure and flow in vivo have also been reported to lead to significant changes in lymphangion function. Because changes in pressure and flow are both cause and effect of adaptive processes, characterizing adaptation requires a more fundamental analysis of lymphatic muscle properties. Therefore, the purpose of the present work was to use an intact lymphangion isovolumetric preparation to evaluate changes in mesenteric lymphatic muscle mechanical properties and the intracellular Ca(2+) in response to sustained mesenteric venous hypertension. Bovine mesenteric veins were surgically occluded to create mesenteric venous hypertension. Postnodal mesenteric lymphatic vessels from mesenteric venous hypertension (MVH; n = 6) and sham surgery (Sham; n = 6) animals were isolated and evaluated 3 days after the surgery. Spontaneously contracting MVH vessels generated end-systolic active tension and end-diastolic active tension lower than the Sham vessels. Furthermore, steady-state active tension and intracellular Ca(2+) concentration levels in response to KCl stimulation were also significantly lower in MVH vessels compared with those of the Sham vessels. There was no significant difference in passive tension in lymphatic vessels from the two groups. Taken together, these results suggest that following 3 days of mesenteric venous hypertension, postnodal mesenteric lymphatic vessels adapt to become weaker pumps with decreased cytosolic Ca(2+) concentration.

Adaptation of mesenteric lymphatic vessels to prolonged changes in transmural pressure.

In vitro studies have revealed that acute increases in transmural pressure increase lymphatic vessel contractile function. However, adaptive responses to prolonged changes in transmural pressure in vivo have not been reported. Therefore, we developed a novel bovine mesenteric lymphatic partial constriction model to test the hypothesis that lymphatic vessels exposed to higher transmural pressures adapt functionally to become stronger pumps than vessels exposed to lower transmural pressures. Postnodal mesenteric lymphatic vessels were partially constricted for 3 days. On postoperative day 3, constricted vessels were isolated, and divided into upstream (UP) and downstream (DN) segment groups, and instrumented in an isolated bath. Although there were no differences between the passive diameters of the two groups, both diastolic diameter and systolic diameter were significantly larger in the UP group than in the DN group. The pump index of the UP group was also higher than that in the DN group. In conclusion, this is the first work to report how lymphatic vessels adapt to prolonged changes in transmural pressure in vivo. Our results suggest that vessel segments upstream of the constriction adapt to become both better fluid conduits and lymphatic pumps than downstream segments.

Evaluation of gravimetric techniques to estimate the microvascular filtration coefficient.

Microvascular permeability to water is characterized by the microvascular filtration coefficient (K(f)). Conventional gravimetric techniques to estimate K(f) rely on data obtained from either transient or steady-state increases in organ weight in response to increases in microvascular pressure. Both techniques result in considerably different estimates and neither account for interstitial fluid storage and lymphatic return. We therefore developed a theoretical framework to evaluate K(f) estimation techniques by 1) comparing conventional techniques to a novel technique that includes effects of interstitial fluid storage and lymphatic return, 2) evaluating the ability of conventional techniques to reproduce K(f) from simulated gravimetric data generated by a realistic interstitial fluid balance model, 3) analyzing new data collected from rat intestine, and 4) analyzing previously reported data. These approaches revealed that the steady-state gravimetric technique yields estimates that are not directly related to K(f) and are in some cases directly proportional to interstitial compliance. However, the transient gravimetric technique yields accurate estimates in some organs, because the typical experimental duration minimizes the effects of interstitial fluid storage and lymphatic return. Furthermore, our analytical framework reveals that the supposed requirement of tying off all draining lymphatic vessels for the transient technique is unnecessary. Finally, our numerical simulations indicate that our comprehensive technique accurately reproduces the value of K(f) in all organs, is not confounded by interstitial storage and lymphatic return, and provides corroboration of the estimate from the transient technique.

Balance point characterization of interstitial fluid volume regulation.

The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure (P(i)) and protein concentrations (C(i)) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P(i) and C(i) as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P(i) and C(i) arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P(i) and C(i) result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P(i) is unaffected by interstitial compliance. These simple algebraic solutions predict P(i) and C(i) that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.

Long-term effects of increased dietary polyunsaturated fat from walnuts on metabolic parameters in type II diabetes.

BACKGROUND/OBJECTIVES: Most dietary interventions have metabolic effects in the short term, but long-term effects may require dietary fat changes to influence body composition and insulin action. This study assessed the effect of sustained high polyunsaturated fatty acids (PUFA) intake through walnut consumption on metabolic outcomes in type II diabetes. SUBJECTS/METHODS: Fifty overweight adults with non-insulin-treated diabetes (mean age 54+/-8.7 years) were randomized to receive low-fat dietary advice +/-30 g per day walnuts targeting weight maintenance (around 2000 kcal, 30% fat) for 1 year. Differences between groups were assessed by changes in anthropometric values (body weight, body fat, visceral adipose tissue) and clinical indicators of diabetes over treatment time using the general linear model. RESULTS: The walnut group consumed significantly more PUFA than the control (P=0.035), an outcome attributed to walnut consumption (contributing 67% dietary PUFA at 12 months). Most of the effects were seen in the first 3 months. Despite being on weight maintenance diets, both groups sustained a 1-2 kg weight loss, with no difference between groups (P=0.680). Both groups showed improvements in all clinical parameters with significant time effects (P<0.004), bar triacylglycerol levels, but these were just above normal to begin with. The walnut group produced significantly greater reductions in fasting insulin levels (P=0.046), an effect seen largely in the first 3 months. CONCLUSIONS: Dietary fat can be manipulated with whole foods such as walnuts, producing reductions in fasting insulin levels. Long-term effects are also apparent but subject to fluctuations in dietary intake if not of the disease process.

Prevention of venous thromboembolism: improving practice in surgical patients.

AIMS: Venous thromboembolism (VTE) is the most common preventable cause of hospital-related mortality. There are major inadequacies internationally in administering appropriate prophylaxis. Our initial aim was to show whether our local effectiveness of administration was equally poor. With local inadequacy confirmed, our second aim was to design, implement and evaluate the efficacy of a new VTE protocol nested within a surgical clerking proforma. METHODS: A pilot audit of the prescription and administration of enoxaparin and thromboembolic deterrent stockings for VTE prophylaxis in 51 acutely admitted surgical inpatients (Round 1) was performed against local guidelines derived from the American College of Chest Physicians (ACCP) criteria. The authors then designed and implemented a VTE prevention protocol incorporating risk assessment and decision support within a new clerking proforma for acute surgical admissions. Local practice was audited against the same criteria in Round 2, which comprised 60 consecutive acute surgical admissions in the same district general hospital. RESULTS: In the pilot study, only (19/51) 37% of subjects received appropriate VTE prophylaxis. Over half of patients were at high risk for VTE; 18/29 high risk patients and 4/10 medium risk patients were not adequately protected. Following implementation of the quality improvement intervention, (53/60) 88% of subjects received appropriate prophylaxis (p<0.001). CONCLUSIONS: Implementation of a VTE protocol as part of a clerking proforma for acute surgical admissions is a simple and effective way of ensuring that surgical patients receive appropriate thromboprophylaxis. A similar strategy could be employed to broaden the scope of the National Institute of Clinical Excellence (NICE) guidelines to address VTE prevention in all hospitalised patients.

Opposition splint for partial thumb amputation: a case study measuring disability before and after splint use.

STUDY DESIGN: Case report. INTRODUCTION: A combined burn and a partial amputation can be extremely debilitating as the thumb constitutes 40% of the entire hand when evaluating functional impairment. PURPOSE OF THE STUDY: Measure disability with and without opposition splint use after partial thumb amputation due to a burn. METHODS: Impairment and disability measures were completed at discharge from the hospital and subsequently during outpatient follow-up visits while wearing and not wearing a thumb opposition splint at 3, 6, 8, and 15 months. Comparisons between disability and impairment scores were assessed over time. RESULTS: The difference between DASH scores with and without using the splint were 25 at 3 months, 16 at 6 months, 10 at 8 months, and 12 at 15 months. CONCLUSIONS: Splint use in this case demonstrated clinically significant changes over time with minimal changes in impairment indicating enhanced function and improved patient perception of disability. LEVEL OF EVIDENCE: 4.

Edemagenic gain and interstitial fluid volume regulation.

Under physiological conditions, interstitial fluid volume is tightly regulated by balancing microvascular filtration and lymphatic return to the central venous circulation. Even though microvascular filtration and lymphatic return are governed by conservation of mass, their interaction can result in exceedingly complex behavior. Without making simplifying assumptions, investigators must solve the fluid balance equations numerically, which limits the generality of the results. We thus made critical simplifying assumptions to develop a simple solution to the standard fluid balance equations that is expressed as an algebraic formula. Using a classical approach to describe systems with negative feedback, we formulated our solution as a "gain" relating the change in interstitial fluid volume to a change in effective microvascular driving pressure. The resulting "edemagenic gain" is a function of microvascular filtration coefficient (K(f)), effective lymphatic resistance (R(L)), and interstitial compliance (C). This formulation suggests two types of gain: "multivariate" dependent on C, R(L), and K(f), and "compliance-dominated" approximately equal to C. The latter forms a basis of a novel method to estimate C without measuring interstitial fluid pressure. Data from ovine experiments illustrate how edemagenic gain is altered with pulmonary edema induced by venous hypertension, histamine, and endotoxin. Reformulation of the classical equations governing fluid balance in terms of edemagenic gain thus yields new insight into the factors affecting an organ's susceptibility to edema.

Application of local heat induces capillary recruitment in the Pallid bat wing.

Skin blood flow increases in response to local heat due to sensorineural and nitric oxide (NO)-mediated dilation. It has been previously demonstrated that arteriolar dilation is inhibited with NO synthase (NOS) blockade. Flow, nonetheless, increases with local heat. This implies that the previously unexamined nonarteriolar responses play a significant role in modulating flow. We thus hypothesized that local heating induces capillary recruitment. We heated a portion (3 cm2) of the Pallid bat wing from 25 degrees C to 37 degrees C for 20 min, and measured changes in terminal feed arteriole (approximately 25 microm) diameter and blood velocity to calculate blood flow (n = 8). Arteriolar dilation was reduced with NOS and sensorineural blockade using a 1% (wt/vol) NG-nitro-L-arginine methyl ester (L-NAME) and 2% (wt/vol) lidocaine solution (n = 8). We also measured changes in the number of perfused capillaries, and the time precapillary sphincters were open with (n = 8) and without (n = 8) NOS plus sensorineural blockade. With heat, the total number of perfused capillaries increased 92.7 +/- 17.9% (P = 0.011), and a similar increase occurred despite NOS plus sensorineural blockade 114.4 +/- 30.0% (P = 0.014). Blockade eliminated arteriolar dilation (-4.5 +/- 2.1%). With heat, the percent time precapillary sphincters remained open increased 32.3 +/- 6.0% (P = 0.0006), and this increase occurred despite NOS plus sensorineural blockade (34.1 +/- 5.8%, P = 0.0004). With heat, arteriolar blood flow increased (187.2 +/- 28.5%, P = 0.00003), which was significantly attenuated with NOS plus sensorineural blockade (88.6 +/- 37.2%, P = 0.04). Thus, capillary recruitment is a fundamental microvascular response to local heat, independent of arteriolar dilation and the well-documented sensorineural and NOS mechanisms mediating the response to local heat.

Fli-1 expression in mycosis fungoides.

BACKGROUND: The Fli-1 transcription factor functions in cellular proliferation and tumorigenesis. Its role in various neoplasms and its presence in lymphocytes suggest a link between Fli-1 dysregulation and the pathogenesis of mycosis fungoides (MF). In this study, we further elucidate this possible link. METHODS: Sections from archived specimens were stained using a polyclonal antibody against Fli-1. The percentage of nuclei showing Fli-1 expression was recorded. These were compared with reactive dermatoses. RESULTS: All of the tumor stage lesions showed high levels of nuclear Fli-1 expression. Of plaque stage lesions, six of 12 (50%) showed the same intensity, while the remaining six of 12 varied significantly in their Fli-1 expression. The few patch stage lesions also showed varied expression. CONCLUSION: This study shows diffuse nuclear expression of Fli-1 in all tumor stage MF, whereas expression of this transcription factor varied widely in the early, epidermotropic stages. Although the numbers are too small to draw statistical significance, this study demonstrates an association between increased expression of Fli-1 and progression to tumor stage MF that merits further investigation. Additionally, the mixed expression of Fli-1 in the epidermotropic stages suggests that the role of Fli-1 in MF is related to neoplasia and not epidermotropism.

Local heat produces a shear-mediated biphasic response in the thermoregulatory microcirculation of the Pallid bat wing.

Investigators report that local heat causes an increase in skin blood flow consisting of two phases. The first is solely sensory neural, and the second is nitric oxide mediated. We hypothesize that mechanisms behind these two phases are causally linked by shear stress. Because microvascular blood flow, endothelial shear stress, and vessel diameters cannot be measured in humans, bat wing arterioles (26.6 +/- 0.3, 42.0 +/- 0.4, and 58.7 +/- 2.2 microm) were visualized noninvasively on a transparent heat plate via intravital microscopy. Increasing plate temperature from 25 to 37 degrees C increased flow in all three arterial sizes (137.1 +/- 0.3, 251.9 +/- 0.5, and 184.3 +/- 0.6%) in a biphasic manner. With heat, diameter increased in large arterioles (n = 6) by 8.7 +/- 0.03% within 6 min, medium arterioles (n = 8) by 19.7 +/- 0.5% within 4 min, and small arterioles (n = 8) by 31.6 +/- 2.2% in the first minute. Lidocaine (0.2 ml, 2% wt/vol) and NG-nitro-L-arginine methyl ester (0.2 ml, 1% wt/vol) were applied topically to arterioles (approximately 40 microm) to block sensory nerves, modulate shear stress, and block nitric oxide generation. Local heat caused only a 10.4 +/- 5.5% increase in diameter with neural blockade (n = 8) and only a 7.5 +/- 4.1% increase in diameter when flow was reduced (n = 8), both significantly lower than control (P < 0.001). Diameter and flow increases were significantly reduced with NG-nitro-L-arginine methyl ester application (P < 0.05). Our novel thermoregulatory animal model illustrates 1) regulation of shear stress, 2) a nonneural component of the first phase, and 3) a shear-mediated second phase. The time course of dilation suggests that early dilation of small arterioles increases flow and enhances second-phase dilation of the large arterioles.

A comparison between the short term and long term benefits of screening for abdominal aortic aneurysms from the Huntingdon Aneurysm screening programme.

BACKGROUND: The UK Multicentre Aneurysm Screening Study (MASS) showed a 44% reduction in AAA-related mortality after 4 years and predicted an increased number of deaths prevented in the longer term. We aim to compare the 5 and 13 years benefit from aneurysm screening in the Huntingdon Aneurysm screening programme. METHODS: Incidence and mortality of ruptured AAA (RAAA) after 5 and 13 years of screening in a population based aneurysm screening program. RESULTS: Five years of screening resulted in a reduction in the incidence of RAAA of 49% (95% CI: 3-74%). Nine out of 11 ruptures in the invited group did not survive (mortality 82%; 95% CI: 48-98%) compared to 38 non-survivors from 51 ruptures in the control group (mortality 75%; 95% CI: 60-86%). Five years of screening resulted in an RAAA-related mortality reduction of 45% (95% CI: -15 to 74%). After 13 years of screening the incidence of RAAA was reduced by 73% (95% CI: 58-82%). Twenty-one out of 29 ruptures in the invited group did not survive (mortality 72%; 95% CI: 53-87%) compared to 64 non-survivors from 82 ruptures in the control group (mortality 78%; 95% CI: 68-86%). Thirteen years screening resulted in a reduction of mortality from RAAA of 75% (95% CI: 58-84%). The number needed to screen to prevent one death reduced from 1380 after 5 years to 505 after 13 years. The number of elective AAA operations needed to prevent one death reduced from 6 after 5 years to 4 after 13 years. CONCLUSION: AAA screening becomes increasingly beneficial as screening continues over the longer term. Benefits continue to increase after screening has ceased.

ACE inhibitors increase type III collagen synthesis: a potential explanation for reduction in acute vascular events by ACE inhibitors.

INTRODUCTION: Large trials have shown that angiotensin converting enzyme inhibitor (ACE-I) therapy reduces the risk of myocardial infarction and stroke. Acute vascular events are thought to be initiated by plaque rupture. Animal models of atherosclerosis show an increase in extra cellular matrix when given ACE-I therapy. ACE-I therapy could influence collagen synthesis, one of the major constituents of the atherosclerotic cap. METHODS: A nested case-control study was performed within the Huntingdon Aneurysm Screening Project. Subjects were assessed for arterial disease, drug history and smoking. Blood samples were taken for a measure of collagen synthesis, the amino-terminal propeptide of type III procollagen (PIIINP), lipid levels, iron metabolism and cotinine levels. RESULTS: Information was available for 420 subjects. Thirty-five were taking ACE-I therapy and 385 were not. Mean serum PIIINP level was 3.5 microg/l (sd 1.3 microg/l, range: 1.7-16.5 microg/l. There was a marked increase in mean collagen turnover between subjects taking ACE-I therapy compared to those not. Mean PIIINP level for cases and controls was 4.26 microg/l (95% CI: 3.73-4.79 microg/l) versus 3.61 microg/l (95% CI: 3.48-3.75 microg/l). No differences were found for patients taking other antihypertensive drugs. After adjusting for age, weight, height, lipid levels and ferritin, PIIINP levels remained significantly higher in cases than controls: 4.14 microg/l (95% CI: 3.72-4.57 microg/l) versus 3.62 microg/l (95% CI: 3.49-3.75 microg/l) (P-value 0.02). DISCUSSION: These results suggest that ACE-I therapy up-regulates collagen synthesis, and could improve plaque stabilisation. This may provide an explanation for the decrease in acute vascular events observed in patients on ACE-I therapy.

Strategies to improve the effectiveness of abdominal aortic aneurysm screening programmes.

OBJECTIVE: Ruptured abdominal aortic aneurysms (rAAAs) occurring in patients with screen-detected aneurysms could be regarded as a failure of screening and reduce effectiveness of screening. To understand this issue, we studied the reasons why rAAAs occur in screened patients and estimated the cost-benefit ratio if these ruptures could be prevented. METHODS: All rAAAs occurring in the Huntingdon district in the UK during the study period (1991-2000) were traced via a combination of hospital admission, accident and emergency attendance, and intensive therapy unit admission records, operating theatre registers and post-mortem reports. Cross-referencing with the aneurysm-screening database identified those patients who had attended screening. Previously used cost-effectiveness models were used to estimate the cost benefits to screening. RESULTS: Ninety-three rAAAs occurred in men over the study period, of whom 23 (25%) had been invited for screening and 13 (14%) had accepted the invitation. All who had been screened (mean age 75 [65-82]) had abnormal aortic diameters (>30 mm) on their first scan. Of those invited, 10/23 (43%) did not attend their screening appointment, 4/23 (17%) were deemed not fit for open surgery, 4/23 (17%) ruptured whilst being assessed for aneurysm repair, 2/23 (9%) ruptured whilst under six-monthly surveillance, and 3/23 (13%) failed to attend scheduled six-monthly surveillance appointments. Reducing screened ruptures by one half could increase the cost-effectiveness of screening by 27%. CONCLUSION: There were no failures of the screening test. The benefits of aneurysm screening can be improved by increasing the uptake of screening, the compliance with surveillance, and by streamlining the work-up process before surgery.

Optimal lymphatic vessel structure.

Lymphatic vessels transport excess interstitial fluid from the low-pressure tissues to the higher pressure veins. The basic structural unit of lymphatic vessels is the lymphangion, a segment of the vessel separated by two unidirectional valves. Lymphangions cyclically contract like ventricles and can actively pump lymph. Lymphangions, as conduit vessels, also can act as arteries, and resist lymph flow. Functional parameters such as pressures, flow, and efficiency are determined by structural parameters like length, radius, and wall thickness. Since these structural parameters are unalterable experimentally, we developed a computational model to study the effect of a particular structural parameter, lymphangion length, to a particular functional variable, lymph flow. The model predicts that flow is a bimodal function of length, exhibiting an optimal length in the same order of magnitude as that observed experimentally. In essence, when the length to radius ratio is small, lymphangions act more like ventricles, where longer lengths yield greater chamber volume and thus lymph pumped. When the length to radius ratio is large, lymphangions act more like arteries, where longer lengths yield greater resistances to flow. This approach provides the means to explore how lymphatic vessel structure is optimized in a variety of conditions.

LDL cholesterol is associated with small abdominal aortic aneurysms.

OBJECTIVE: To examine the relationship between serum lipids and abdominal aortic aneurysms (AAA). METHODS: Two hundred and six males (>50 years) with AAA (> or =30 mm) detected in a population based screening programme were compared with 252 age-matched male controls in a nested case-control study. Smoking status, previous medical and family histories, height, weight, blood pressure, ankle brachial pressure index (ABPI) and non-fasting lipid profile were recorded. RESULTS: Cases were found to have significantly higher LDL cholesterol than controls. LDL cholesterol was an independent predictor of the risk for aneurysms in a logistic regression model adjusting for smoking status, family history of AAA, history of ischaemic heart disease, presence of peripheral vascular disease, use of lipid lowering medication and treatment for hypertension. There was a linear effect with increased levels of LDL cholesterol increasing the risk of having a small aneurysm (test for trend p=0.03). CONCLUSION: The highly significant association between LDL cholesterol and small aneurysms suggests that LDL, possibly acting via inflammatory mediated matrix degeneration, could be an initiating factor in the development of AAA. The ability of statin therapy to prevent AAA formation requires further investigation.