Structure-function studies of the C3/C5 epimerases and C4 reductases of the Campylobacter jejuni capsular heptose modification pathways.

Many bacteria produce polysaccharide-based capsules that protect them from environmental insults and play a role in virulence, host invasion, and other functions. Understanding how the polysaccharide components are synthesized could provide new means to combat bacterial infections. We have previously characterized two pairs of homologous enzymes involved in the biosynthesis of capsular sugar precursors GDP-6-deoxy-D-altro-heptose and GDP-6-OMe-L-gluco-heptose in Campylobacter jejuni. However, the substrate specificity and mechanism of action of these enzymes-C3 and/or C5 epimerases DdahB and MlghB and C4 reductases DdahC and MlghC-are unknown. Here, we demonstrate that these enzymes are highly specific for heptose substrates, using mannose substrates inefficiently with the exception of MlghB. We show that DdahB and MlghB feature a jellyroll fold typical of cupins, which possess a range of activities including epimerizations, GDP occupying a similar position as in cupins. DdahC and MlghC contain a Rossman fold, a catalytic triad, and a small C-terminal domain typical of short-chain dehydratase reductase enzymes. Integrating structural information with site-directed mutagenesis allowed us to identify features unique to each enzyme and provide mechanistic insight. In the epimerases, mutagenesis of H67, D173, N121, Y134, and Y132 suggested the presence of alternative catalytic residues. We showed that the reductases could reduce GDP-4-keto-6-deoxy-mannulose without prior epimerization although DdahC preferred the pre-epimerized substrate and identified T110 and H180 as important for substrate specificity and catalytic efficacy. This information can be exploited to identify inhibitors for therapeutic applications or to tailor these enzymes to synthesize novel sugars useful as glycobiology tools.

Relationship Between Physiological and Perceived Fall Risk in People With Multiple Sclerosis: Implications for Assessment and Management.

OBJECTIVE: This study evaluated the relationship between physiological and perceived fall risk in people with multiple sclerosis (MS). DESIGN: Secondary analysis of data from prospective cohort studies undertaken in Australia, the United Kingdom, and the United States. SETTING: Community. PARTICIPANTS: Ambulatory people with MS (N=416) (age 51.5±12.0 years; 73% female; 62% relapsing-remitting MS; 13.7±9.9 years disease duration). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: All participants completed measures of physiological (Physiological Profile Assessment [PPA]) and perceived (Falls Efficacy Scale-international [FESi]) fall risk and prospectively recorded falls for 3 months. RESULTS: 155 (37%) of the participants were recurrent fallers (≥2 falls). Mean PPA and FESi scores were high (PPA 2.14±1.87, FESi 34.27±11.18). The PPA and the FESi independently predicted faller classification in logistic regression, which indicated that the odds of being classified as a recurrent faller significantly increased with increasing scores (PPA odds ratio [OR] 1.30 [95% CI 1.17-1.46], FESi OR 1.05 [95% CI 1.03-1.07]). Classification and regression tree analysis divided the sample into four groups based on cutoff values for the PPA: (1) low physiological/low perceived risk (PPA <2.83, FESi <27.5), (2) low physiological/high perceived risk (PPA <2.83, FESi >27.5), (3) high physiological/low perceived risk (PPA >2.83, FESi <35.5), and (4) high physiological/high perceived risk (PPA <2.83, FESi >35.5). Over 50% of participants had a disparity between perceived and physiological fall risk; most were in group 2. It is possible that physiological risk factors not detected by the PPA may also be influential. CONCLUSIONS: This study highlights the importance of considering both physiological and perceived fall risk in MS and the need for further research to explore the complex interrelationships of perceptual and physiological risk factors in this population. This study also supports the importance of developing behavioral and physical interventions that can be tailored to the individual's needs.

Impact of systemic antimicrobial therapy on mucosal staphylococci in a population of dogs in Northwest England.

BACKGROUND: Antimicrobial-resistant bacteria are increasingly isolated from veterinary patients. OBJECTIVES: To determine risk factors for antimicrobial resistance (AMR) among canine mucosal staphylococci following routine antimicrobial treatment with cefalexin (CFX), clavulanate-amoxicillin (AC), cefovecin (CVN), clindamycin (CD) or a fluoroquinolone (FQ). ANIMALS: Mucosal swab samples (n = 463) were collected from 127 dogs pre-treatment, immediately, and at one- and three-months post-treatment. METHODS: Staphylococci were identified phenotypically and biochemically as coagulase negative (CoNS) or coagulase positive (CoPS); CoPS were speciated by nuc gene PCR. Antimicrobial susceptibility was determined using disc diffusion and mecA gene carriage by PCR. Multilevel, multivariable models examined associations between risk factors and presence/absence of CoPS, meticillin resistance (MR), multidrug-resistance (MDR) and fluoroquinolone resistance (FQR). RESULTS: The percentage of samples with CoNS increased and with CoPS (including S. pseudintermedius) decreased immediately post-treatment with CFX, CVN and CD (P ≤ 0.001) and one month post-treatment with CD (P = 0.003). By three months post-treatment, there was no significant difference compared to pre-treatment samples. Immediately post-treatment with FQs there was significantly increased risk of isolating MRS (P = 0.002), MDR (P = 0.002) or FQR (P = 0.013) staphylococci and of MDR following CFX treatment (P = 0.019). The percentage of samples with AMR staphylococci declined from immediately to three months post-treatment and there was no significant difference between resistance prevalence at one or three months post-treatment for most AMR traits and treatment groups. Exceptions include increased MDR following FQ (P = 0.048) or CFX (P = 0.021), at one and three months post-treatment, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic antimicrobials impact on mucosal staphylococci. Immediately after therapy, the mucosa may be a reservoir for AMR staphylococci that are a source of mobile genetic elements carrying AMR genes.

Haplotype analysis finds linkage disequilibrium in the IL-12 gene in patients with HCV.

HCV is a major cause of liver disease worldwide. IL-12 plays an essential role in the balance of T helper 1 (Th1) differentiation versus a T helper 2 (Th2) driven response from its naïve precursor. Linkage disequilibrium measures the degree to which alleles at two loci are associated and the non-random associations between alleles at two loci. Haplotypes of the three IL-12B loci studied were determined in the patient cases and the normal healthy control subjects. The frequency of the 12 possible IL-12B haplotypes on the 3 loci was determined in subjects heterozygous at only one of the loci within the studied haplotype. Haplotype frequencies were compared between the patient groups and controls (n = 49) to determine if any preferential combination of markers occurred using chi-squared and applying the Bonferroni correction. 45 HCV RNA negative patients; 88 HCV RNA positive patients; and 15 uninfected cases at high risk of HCV infection (EU) were studied. The haplotype "C" SNP of the 3'UTR with the "E" 4 bp deletion of the intron 4 region was in linkage disequilibrium (χ(2) = 45.15, P < 0.001, 95% CL). The haplotype analysis of the insertion allele of the promoter with the deletion allele of the intron 4("E") IL-12B polymorphism showed linkage disequilibrium (χ(2) = 5.64, P = 0.02). Linkage disequilibrium of polymorphisms is reported in the IL-12 gene in patients with HCV infection and contributes to the understanding of patient genotype and expected production of IL-12, responding to infection.

Polymorphic differences in SOD-2 may influence HCV viral clearance.

Hepatitis C virus (HCV) is a pathogen causing chronic hepatitis, cirrhosis, and liver cancer occurring in about 3% of the world's population. Most individuals infected with HCV develop persistent viremia. Oxidative stress may play an important role in the pathogenesis of a number of diseases including HCV infection and diabetes mellitus. Polymorphisms in the antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in HCV and/or in its complications. Patients with HCV and normal, healthy controls were investigated for a superoxide dismutase (SOD-2) polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution. Polymorphisms in antioxidant gene SOD-2 were carried out by PCR, restriction fragment length polymorphism assays and by polyacrylamide gel electrophoresis. For the SOD-2 polymorphism, the RNA positive group showed a higher percentage of "CT" genotype than the RNA negative group (89.3% vs. 66.1%, P = 0.001, χ(2) = 11.9). The RNA negative group had more TT genotypes than the RNA positive group (27.4% vs. 6.80%, P = 0.01, χ(2) = 11.6). The exposed uninfected group had an increased frequency of the "CT" genotype (86.2% vs. 66.1%, P = 0.02, χ(2) = 5.5). The RNA positives had a higher frequency of the "CT" from the normal controls (72.1% vs. 89.2%, P = 0.005, χ(2) = 7.8).

Comparison of the sequential organ failure assessment score with the King's College Hospital criteria and the model for end-stage liver disease score for the prognosis of acetaminophen-induced acute liver failure.

Acetaminophen-induced acute liver failure (ALF) is a complex multiorgan illness. An assessment of the prognosis is essential for the accurate identification of patients for whom survival without liver transplantation (LT) is unlikely. The aims of this study were the comparison of prognostic models [King's College Hospital (KCH), Model for End-Stage Liver Disease, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II)] and the identification of independent prognostic indicators of outcome. We evaluated consecutive patients with severe acetaminophen-induced ALF who were admitted to the intensive care unit. At admission, demographic, clinical, and laboratory parameters were recorded. The discriminative ability of each prognostic score at the baseline was evaluated with the area under the receiver operating characteristic curve (AUC). In addition, using a multiple logistic regression, we assessed independent factors associated with outcome. In all, 125 consecutive patients with acetaminophen-induced ALF were evaluated: 67 patients (54%) survived with conservative medical management (group 1), and 58 patients (46%) either died without LT (28%) or underwent LT (18%; group 2). Group 1 patients had significantly lower median APACHE II (10 versus 14) and SOFA scores (9 versus 12) than group 2 patients (P < 0.001). The independent indicators associated with death or LT were a longer prothrombin time (P = 0.007), the inspiratory oxygen concentration (P = 0.005), and the lactate level at 12 hours (P < 0.001). The KCH criteria had the highest specificity (83%) but the lowest sensitivity (47%), and the SOFA score had the best discriminative ability (AUC = 0.79). In conclusion, for patients with acetaminophen-induced ALF, the SOFA score performed better than the other prognostic scores, and this reflected the presence of multiorgan dysfunction. A further evaluation of SOFA with the KCH criteria is warranted.

Axillary intra-aortic balloon pump, biventricular assist device implantation and subsequent orthotopic heart transplantation in a patient with sickle cell trait.

A 38-year-old male with sickle cell trait and acute refractory heart failure received an axillary intra-aortic balloon pump and short-term biventricular assist device. He underwent orthotopic heart transplantation 45 days later, which was complicated by major bleeding necessitating significant intra-operative transfusion. Support with veno-arterial extracorporeal membrane oxygenation was provided and successfully weaned five days later. He made a full recovery and remains alive and well 34 months after discharge. We hypothesize that the protective peri-operative measures undertaken, including normothermia during surgery and post-operative haemodynamic stability due to the use of mechanical circulatory support, conveyed a degree of protection against complications associated with sickle cell dysfunction and contributed to the successful outcome.

Financial implications of using extracorporeal membrane oxygenation following heart transplantation.

OBJECTIVES: Primary graft dysfunction after heart transplant is associated with high morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) can be used to wean patients from cardiopulmonary bypass. This study retrospectively reviews a single-centre experience of post-transplant ECMO in regard to outcomes and associated costs. METHODS: Between May 2006 and May 2019, a total of 267 adult heart transplants were performed. We compared donor and recipient variables, ECMO duration and the incidence of renal failure, bleeding, infection and cost analysis between ECMO and non-ECMO groups. RESULTS: ECMO support was required postoperatively to manage primary graft dysfunction in 72 (27%) patients. The mean duration of ECMO support was 6 ± 3.2 days. Mean ischaemic times were similar between the groups. There was a significantly higher proportion of ventricular assist device explant to transplant in the ECMO group versus non-ECMO (38.2% vs 14.1%; P < 0.0001). ECMO patients had a longer duration of stay in the intensive care unit (P < 0.0001) and total hospital stay (P < 0.0001). Greater mortality was observed in the ECMO group (P < 0.0001). The median cost of providing ECMO was £18 000 [interquartile range (IQR): £12 750-£24 000] per patient with an additional median £35 225 (IQR: £21 487.25-£51 780.75) for ITU stay whilst on ECMO. The total median cost per patient inclusive of hospital stay, ECMO and dialysis costs was £65 737.50 (IQR: £52 566.50-£95 221.75) in the non-ECMO group compared to £145 415.71 (IQR: £102 523.21-£200 618.96) per patient in the ECMO group (P < 0.0001). CONCLUSIONS: Patients with primary graft dysfunction following heart transplantation who require ECMO are frequently bridged to a recovery; however, the medium and longer-term survival for these patients is poorer than for patients who do not require ECMO.

Combining enteral with parenteral nutrition to improve postoperative glucose control.

The provision of parenteral nutrition (PN) to 'stressed' patients often results in hyperglycaemia, which may be detrimental. In animal models limited amounts of enteral nutrition (EN) improve intestinal integrity and stimulate intestinal incretin production, which may lead to improved glucose control. We set out to assess if combining EN with PN results in improved glucose homeostasis rather than PN given alone. We conducted a randomised trial in a university teaching hospital of patients undergoing a 'curative' oesophagectomy for adenocarcinoma. Differences between the two intervention groups were assessed for continuous glucose measurement, insulin sensitivity using insulin tolerance tests (ITT) and homeostasis model analysis (HOMA), the incretin glucose-dependent insulinotropic polypeptide (GIP) and intestinal permeability. The combination of PN with EN resulted in lower interstitial glucose concentrations (P = 0.002), reduced insulin resistance, improved insulin sensitivity (HOMA-insulin resistance (IR) P = 0.045; HOMA beta P = 0.037; ITT P = 0.006), improved intestinal permeability (P < 0.001) and increased GIP (P = 0.01) when compared with PN alone. The combination of EN with PN, when compared with PN alone, results in reduced glucose concentrations, reduced insulin resistance, increased incretins and improvements in intestinal permeability.

Longitudinal impact of temporary mechanical circulatory support on durable ventricular assist device outcomes: An IMACS registry propensity matched analysis.

BACKGROUND: Patients with advanced heart failure and cardiogenic shock (CS) often require temporary circulatory support (TCS) as a bridge to durable ventricular assist devices (dVADs). We aim to characterize longitudinal outcomes of patients with and without CS. METHODS: Between 2013 and 2017, 13,813 adult patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 1 to 3 with continuous flow left ventricular assist devices or biventricular assist devices were registered into the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support. Patients were sub-grouped according to support type (extracorporeal membrane oxygenation [ECMO], intra-aortic balloon pump [IABP], and other TCS). Other TCS included all other surgical and percutaneous TCS devices. Estimated survival was compared based on need for pre-operative TCS and by profile. RESULTS: Pre-operative TCS was used in 5,632 (41%) cases. Of these, ECMO was used in 1,138 (20%) cases, IABP in 3,901 (69%) cases, and other TCS in 595 (11%) cases. Patients requiring ECMO had greater needs for biventricular support after dVAD (22% ECMO, 5% IABP, and 7% other TCS; p < 0.001) with longer post-implant intensive care stays (ECMO 24 days, IABP 14 days, and other TCS 12 days; p < 0.001). INTERMACS Profile 1 to 3 patients with pre-implant ECMO had the lowest longitudinal survival (82% at 1 month and 44% at 48 months) compared with IABP (93% at 1 month and 51% at 48 months), other TCS (92% at 1 month and 52% at 48 months), and non-TCS (95% at 1 months and 55 % at 48 months) (p < 0.0001). Propensity score matching analysis of the pre-implant ECMO INTERMACS Profile 1 group when compared with alternative pre-implant TCS strategies had an associated higher hazard impacting early phase survival vs other TCS (hazard ratio, 1.80; p < 0.01) and IABP (hazard ratio, 1.65; p < 0.01). CONCLUSIONS: In advanced heart failure with patients with CS, the use of ECMO before dVAD was associated with lower longitudinal survival and increased utilization of biventricular support compared with alternative TCS strategies. Research focused on longitudinal profiling in CS and pre-implant TCS is warranted to further understand these differences.

Short- and long-term adverse events in patients on temporary circulatory support before durable ventricular assist device: An IMACS registry analysis.

BACKGROUND: Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival rates after implantation of durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival rates in patients requiring pre-operative TCS. METHOD: We analyzed 13,511 adults (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] Profiles 1-3) with continuous-flow dVADs in International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (2013-2017) according to the need for pre-operative TCS (n = 5,632) vs no TCS (n = 7,879). Of these, 726 (5.4%) had biventricular assist devices (BiVAD). Furthermore, we compared prevalent rates (events/100 patient-months) of bleeding, device-related infection, hemorrhagic and ischemic cerebrovascular accidents (hemorrhagic cerebral vascular accident [hCVA], and ischemic cerebral vascular accident [iCVA]) in early (<3 months) and late (≥3 months) post-operative periods. RESULTS: TCS included extracorporeal membrane oxygenation (ECMO) (n = 1,138), intra-aortic balloon pump (IABP) (n = 3,901), and other TCS (n = 593). Within 3 post-operative months, there were more major bleeding and cerebrovascular accidents (CVAs) in patients with pre-operative ECMO (events/100 patient-months rates: bleeding = 19, hCVA = 1.6, iCVA = 2.8) or IABP (bleeding = 17.3, hCVA = 1.5, iCVA = 1.5) vs no TCS (bleeding = 13.2, hCVA = 1.1, iCVA = 1.2, all p < 0.05). After 3 months, adverse events were lower and similar in all groups. Patients with ECMO had the worst short- and long-term survival rates. Patients with BiVAD had the worst survival rate regardless of need for pre-operative TCS. CVA and multiorgan failures were the common causes of death for patients with TCS and patients without TCS. CONCLUSIONS: Patients requiring TCS before dVAD had a sicker phenotype and higher rates of early post-operative adverse events than patients without TCS. ECMO was associated with very high early ischemic stroke, bleeding, and mortality. The extreme CS phenotype needing ECMO warrants a higher-level profile status, such as INTERMACS "0."

Continuous renal replacement therapy (CRRT) in patients with liver disease: is circuit life different?

BACKGROUND/AIMS: Clotting of haemofiltration circuits is a major complication of continuous renal replacement therapies (CRRT), yet systemic anticoagulation risks haemorrhage. Traditionally, patients with liver failure are managed with no or minimal anticoagulation, because of abnormal clotting tests and the perceived, increased bleeding risk. METHODS: We retrospectively reviewed CRRT circuit life in 50 patients; 3 groups of liver failure patients treated with CRRT (acute liver failure (ALF), acute on chronic liver disease (ACLD) and post-elective liver transplantation (LTx)), with two control groups; systemic sepsis (SS) and haematological malignancy (Haem). RESULTS: CCRT circuit life was significantly greater in the Haem group, compared to the others; 24.3+/-23.9h, vs. 11+/-10.5 ALF, 11.6+/-6.6 ACLF, 7.4+/-5.1 LTx and 9.2+/-6.5 SS, p<0.05, with Haem group requiring fewest new CCRT circuits within 48h; 2.4+/-1.0 vs. 4.3+/-1.3 ALF, 4.2+/-2.1 ACLF, 5.3+/-1.5 LTx and 4.6+/-1.5 SS, p<0.05 and least blood transfusions; 1.2+/-1.3 vs. 4.8+/-4.2 ALF, 4.2+/-4.1 ACLF, 2.2+/-2.1 LTx and 3.0+/-1.5 SS. Transmembrane pressures were higher in those CCRT circuits with haemofilter/dialyzer clotting, compared to other causes, such as access dysfunction (123+/-74 vs. 71.8+/-29.3 mm Hg, p=0.009). In those patients in whom anticoagulation was started due to repeated filter clotting, circuit life improved from 5.6+/-3.4 to 19+/-12.7h, p<0.01. CONCLUSION: Despite abnormal laboratory coagulation tests and thrombocytopenia, CCRT circuits clot frequently in liver failure patients. Anticoagulation did improve CRRT circuit survival without an obvious increase in bleeding or blood transfusion requirement. Thus anticoagulation should be considered in these patients with repeated circuit clotting.

RIFLE classification as predictive factor of mortality in patients with cirrhosis admitted to intensive care unit.

BACKGROUND AND AIM: To evaluate the association of the Risk, Injury, Failure, Loss and End-stage renal failure (RIFLE) score on mortality in patients with decompensated cirrhosis admitted to intensive care unit (ICU). METHODS: A cohort of 412 patients with cirrhosis consecutively admitted to ICU was classified according to the RIFLE score. Multivariable logistic regression analysis was used to evaluate the factors associated with mortality. Liver-specific, Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) and RIFLE scores on admission, were compared by receiver-operator characteristic curves. RESULTS: The overall mortality during ICU stay or within 6 weeks after discharge from ICU was 61.2%, but decreased over time (76% during first interval, 1989-1992 vs 50% during the last, 2005-2006, P < 0.001). Multivariate analysis showed that RIFLE score (odds ratio: 2.1, P < 0.001) was an independent factor significantly associated with mortality. Although SOFA had the best discrimination (area under receiver-operator characteristic curve = 0.84), and the APACHE II had the best calibration, the RIFLE score had the best sensitivity (90%) to predict death in patients during follow up. CONCLUSIONS: RIFLE score was significantly associated with mortality, confirming the importance of renal failure in this large cohort of patients with cirrhosis admitted to ICU, but it is less useful than other scores.

Prognostic models in cirrhotics admitted to intensive care units better predict outcome when assessed at 48 h after admission.

BACKGROUND AND AIM: The accuracy of prognostic models in critically ill cirrhotics at admission to intensive care units (ICU) may be unreliable. Predictive accuracy could be improved by evaluating changes over time, but this has not been published. The aim of the present study was to assess the performance of prognostic models in cirrhotics at admission (baseline) and at 48 h to predict mortality in the ICU or within 6 weeks after discharge from the ICU. METHODS: One hundred and twenty-eight cirrhotics (77 males, mean age 49 +/- 11.3 years) were consecutively admitted and alive 48 h after admission with 89% on mechanical ventilation, 76% on inotrope support, and 42% with renal failure. Prognostic models used were Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), failing organ systems (FOS) at baseline and at 48 h, Deltascore (difference between baseline and at 48 h) and the mean score (MN - score admission + 48 h/2) which were compared by area under the receiver operating characteristic curves (AUC). RESULTS: Mortality was 54.7% (n = 70) due to multiple organ failure in 55%. CTP, MELD, APACHE II, SOFA and FOS performed better at 48 h (AUC: 0.78, 0.86, 0.78, 0.88 and 0.85, respectively) than at baseline (AUC: 0.75, 0.78, 0.75, 0.81 and 0.79, respectively). The mean score had better discrimination than the baseline score; the Deltascore had poor predictive ability (AUC < 0.70). SOFA score (48 h: 0.88, mean: 0.88) and FOS (mean: 0.88) had the best accuracy, with a SOFA and MN-SOFA > or = 10 predicting mortality in 93% and 91%, respectively, and MN-FOS > or = 1.5 in 98%. CONCLUSIONS: In cirrhotics, prognostic scores in the ICU at 48 h had better discrimination than baseline scores for short-term mortality. SOFA and FOS models had the best performance.

Clinical and magnetic resonance imaging characteristics of quadrigeminal cysts in dogs.

BACKGROUND: Quadrigeminal cysts (QC) are the most common intracranial intra-arachnoid cysts in dogs, primarily affecting small breeds. Clinical significance is controversial. HYPOTHESIS: Male, brachycephalic, small breed dogs are predisposed to QC, and objective measurement of parenchymal compression can distinguish clinically relevant QC from incidental findings. ANIMALS: A total of 4,100 client-owned dogs. METHODS: A retrospective study that recorded signalment, history, clinical signs, and magnetic resonance imaging features. The degree of brain compression was evaluated in the presence of relevant clinical signs. The percentage compression of cerebellum and forebrain was calculated by comparing the expected to the actual diameter and longitudinal dimension, respectively. RESULTS: QC were diagnosed in 28 dogs, of which 21 (75%) were small breed dogs. Fifteen dogs (54%) were brachycephalic. Eighteen dogs were male, and 10 were female. Cerebellar, occipital lobe, or compression in both areas occurred in 86% (24/28 dogs). Clinical signs included focal and generalized seizures in 5 dogs and cerebellar signs in 6 dogs. Mean occipital lobe compression was 17% (SD = 4) in clinically affected and 10% (SD = 3) in normal dogs (P = .006). Occipital lobe compression >14% was always associated with clinical signs. The mean cerebellar compression was 18%, but there was no association between compression and clinical signs. The animals were more likely to develop clinical signs if both areas were compressed (P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Parenchymal compression by QC can be incidental, and other central nervous system diseases must be excluded when assessing the clinical significance of QC. However, occipital lobe compression over 14% is likely to cause clinical signs.

Use and complications of peripheral vascular catheters: a prospective study.

UNLABELLED: Peripheral vascular catheters (PVCs) are important medical devices but their insertion and usage are associated with discomfort and potential complications such as thrombophlebitis. This article looks into the various aspects of the practice of using PVCs, especially their complications and ways of avoiding them. AIMS: to determine the complications (and their associated factors) related to PVCs. DESIGN: prospective. SETTING: District General Hospital. PATIENTS: a study was undertaken of 86 of the 106 patients consecutively admitted as an emergency over a period of two weeks who had a PVC inserted. METHODS AND INTERVENTIONS: the admitting doctors inserted the PVCs at their discretion. PVC sites were inspected daily. ANALYSIS AND RESULTS: of the 86 PVCs inserted, 42 were never used, while 43 were of large gauge and 29 were left in situ for over 72 hours. Eight patients developed thrombophlebitis, of which four had a large gauge PVC, two were never used and two were left in situ for over 72 hours (P=0.016). CONCLUSIONS: incidence of thrombophlebitis may be reduced by re-siting or removing PVCs within 72 hours. PVC gauge and whether it was used, were not associated with this complication.

Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive-care units: prospective two-centre study.

BACKGROUND: Hospital-acquired infection due to meticillin-resistant Staphylococcus aureus (MRSA) is common within intensive-care units. Single room or cohort isolation of infected or colonised patients is used to reduce spread, but its benefit over and above other contact precautions is not known. We aimed to assess the effectiveness of moving versus not moving infected or colonised patients in intensive-care units to prevent transmission of MRSA. METHODS: We undertook a prospective 1-year study in the intensive-care units of two teaching hospitals. Admission and weekly screens were used to ascertain the incidence of MRSA colonisation. In the middle 6 months, MRSA-positive patients were not moved to a single room or cohort nursed unless they were carrying other multiresistant or notifiable pathogens. Standard precautions were practised throughout. Hand hygiene was encouraged and compliance audited. FINDINGS: Patients' characteristics and MRSA acquisition rates were similar in the periods when patients were moved and not moved. The crude (unadjusted) Cox proportional-hazards model showed no evidence of increased transmission during the non-move phase (0.73 [95% CI 0.49-1.10], p=0.94 one-sided). There were no changes in transmission of any particular strain of MRSA nor in handwashing frequency between management phases. INTERPRETATION: Moving MRSA-positive patients into single rooms or cohorted bays does not reduce crossinfection. Because transfer and isolation of critically ill patients in single rooms carries potential risks, our findings suggest that re-evaluation of isolation policies is required in intensive-care units where MRSA is endemic, and that more effective means of preventing spread of MRSA in such settings need to be found.

Attrition and Rape Case Characteristics: A Profile and Comparison of Female Sex Workers and Non-Sex Workers.

The attrition of rape cases from the criminal justice system (CJS) remains high and there is a paucity of research in relation to marginalized groups. Sex workers (SWs) are vulnerable to sexual violence due to the nature of their work. They are also unlikely to report such violence to police for a range of reasons. Two stages of research sought to describe the victim, perpetrator, and offense characteristics of SW rape and to examine the attrition of these cases. All rapes and attempted rapes (N = 1,146) reported to police in a large city in the South West of England over a 21-year period were examined; 67 cases involved SWs. Data were extracted from police files in line with the variables of interest. Secondary analysis of the total number of SW rapes (n = 67) resulted in a profile of these cases. A matched pairs study revealed significant differences in victim, perpetrator, and assault characteristics between SW (n = 62) and non-sex-worker (NSW) samples (n = 62). Although no significant difference was found in terms of attrition from the CJS, SW cases were observed to secure more convictions for rape than NSW cases. The implications of the findings for practice and future research are discussed.

Polymorphisms in the IL-12B gene and outcome of HCV infection.

Most people with hepatitis C virus (HCV) develop chronic infection with persistent viremia. Resolution of infection is associated with antiviral cellular immune responses of T helper 1 (Th1) type. Interleukin-12 (IL-12) is a key cytokine in the generation of Th1 responses, and functionally relevant polymorphisms of the IL12B gene and its promoter have been described recently. We sought an association between three IL12B polymorphisms and outcome of HCV infection in 195 HCV antibody-positive patients; 123 were chronically infected with detectable HCV RNA, and 72 had spontaneously resolved infection testing repeatedly negative for HCV RNA. Genotyping was performed for a single nucleotide polymorphism (SNP) in the 3'-UTR (1188A/C) of the IL12B gene and for 4-bp insertion/deletion polymorphisms in the IL12B promoter region and in the intron 4 region of the IL12B gene. We found chronically infected patients were significantly more likely than those with resolved HCV infection to be homozygous for the 3'-UTR A allele (66% vs. 50%; chi-square = 4.12, p = 0.04 with Yates correction), which has been associated with lower IL-12 production. No other significant association was found. Our findings support the concept that an individual's genetically determined ability to produce IL-12 is another factor that can influence the outcome of HCV infection.