Angiogenic factors and the lectin pathway of complement in women with secondary recurrent pregnancy loss.

The poor remodeling of placental spiral arteries seen in preeclampsia is also discussed to contribute to recurrent pregnancy loss (RPL) preceded by abnormal angiogenesis and excessive complement activation. Low levels of Mannose-binding-lectin (MBL), a pattern recognition molecule (PRM) of the lectin pathway, have been found in women with RPL. We propose that pregnancy loss is connected to defective angiogenesis with reperfusion damage in the placenta and decreased levels of PRM in the lectin pathway in women with RPL. In this cohort study, we investigate the angiogenic factors and the lectin complement pathway in early pregnancy and their time-dependent relationship with pregnancy outcomes in 76 women with secondary RPL (sRPL) who have at least four prior pregnancy losses and a live birth. We evaluated levels of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Vascular Endothelial Growth Factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PRMs, MBL, ficolin-1, -2, -3 and an additional soluble PRM, Pentraxin-3, during the 5th, 6th, and 7th gestational weeks. Our results showed that, compared to live births, pregnancies that ended in loss were associated with elevated VEGF levels and decreased levels of the Ang-2/Ang-1 ratio. Also, increasing levels of ficolin-2 were significantly associated with pregnancy loss, with MBL showing no association. Our research suggests that women with sRPL may have inadequate placentation with impaired angiogenesis in pregnancies ending in a loss.

Effects of Saccharomyces cerevisiae boulardii (CNCM I-1079) on feed intake, blood parameters, and production during early lactation.

The periparturient period is a metabolically demanding time for dairy animals because of increased nutrient requirements for milk yield. The objective of this study was to investigate the effect of feeding Saccharomyces cerevisiae boulardii (CNCM I-1079), a commercial active dry yeast (ADY), in dairy cows on productive and metabolic measures during the periparturient period. Primiparous (n = 33) and multiparous (n = 35) cows were fed a close-up total mixed ration (TMR) before calving and a lactation TMR postpartum. Three weeks before expected calving time, animals were blocked by parity and body weight and then randomly assigned to either control group (control; n = 34) or treatment (ADY; n = 34). All animals were housed in a tie-stall barn with individual feed bunks; the ADY animals received supplementary Saccharomyces cerevisiae boulardii (CNCM I-1079), top dressed daily at a predicted dosage of 1.0 × 1010 cfu (12.5 g) per head. Blood samples were collected weekly along with milk yield and milk composition data; feed intake data were collected daily. Serum samples were analyzed for glucose, nonesterified fatty acid, ß-hydroxybutyrate, haptoglobin (Hp), and the cytokines tumor necrosis factor-α, IL-6, and IL-18. Colostrum samples collected within the first 6 to 10 h were analyzed for somatic cell score and IgG, IgA, and IgM concentrations. Data were analyzed using PROC GLIMMIX in SAS with time as a repeated measure; model included time, parity, treatment, and their interactions. The ADY groups had greater milk yield (39.0 ± 2.4 vs. 36.7 ± 2.3 kg/d) and tended to produce more energy-corrected milk with better feed efficiency. There was no difference in plasma glucose, serum nonesterified fatty acid, serum ß-hydroxybutyrate, Hp, IL-6, or IL-18 due to ADY treatment. The tumor necrosis factor-α increased in ADY-supplemented animals (1.17 ± 0.69 vs. 4.96 ± 7.7 ng/mL), though week, parity, and their interactions had no effect. Serum amyloid A tended to increase in ADY-supplemented animals when compared to control animals and was additionally affected by week and parity; there were no significant interactions. No difference in colostrum IgG, IgA, and IgM was observed between treatments. Supplementing transition cow TMR with ADY (CNCM I-1079) improved milk production and tended to improve efficiency in early lactation; markers of inflammation were also influenced by ADY treatment, though the immunological effect was inconsistent.

Significance of multiple myeloma oncogene 1 immunohistochemistry in chronic endometritis detection in patients with recurrent pregnancy losses: an observational study.

The most reliable chronic endometritis diagnosis is based on immunohistochemistry plasma cell identification in endometrial samples. Our study aimed to compare multiple myeloma oncogene 1 (MUM1) and syndecan-1/CD138 immunohistochemistry staining for chronic endometritis diagnosis among patients with recurrent pregnancy loss. We evaluated the presence of endometrial stromal changes. Fifty-four patients with a history of at least two intrauterine pregnancy losses underwent diagnostic hysteroscopy in the follicular phase of the cycle with endometrial aspiration biopsy. In all 54 cases, three successive sections were cut from each paraffin-embedded tissue block for hematoxylin and eosin (H&E), CD138 and MUM1 staining. The goal was to evaluate the level of agreement between the MUM1 and CD138 results and plasma cell detection rate in assessing the endometrial stromal changes. The concordance analysis between CD138 and MUM1 immunohistochemistry staining showed consistent results in 43 of 54 (79.6%) cases. The level of agreement was moderate, based on a Kappa value of 0.60. MUM1 immunostaining was positive for CE in more cases than CD138 staining, and this difference was statistically significant, showing a higher sensitivity of MUM1 in plasma cell detection (p=0.01). Endometrial stromal changes were observed in the majority of cases - 49/54 (90%). Samples without stromal changes were consistently negative for plasma cells using both CD138 and MUM1 staining. We demonstrated that MUM1 staining, used in conjunction with assessing endometrial stromal changes, contributes to a more accurate and comprehensive diagnosis of chronic endometritis.

Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC).

Drug delivery systems (DDS) for oral delivery of peptide drugs contain excipients that facilitate and enhance absorption. However, little knowledge exists on how DDS excipients such as permeation enhancers interact with the gastrointestinal mucus barrier. This study aimed to investigate interactions of the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC) with ex vivo porcine intestinal mucus (PIM), ex vivo porcine gastric mucus (PGM), as well as with in vitro biosimilar mucus (BM) by profiling their physical and barrier properties upon exposure to SNAC. Bulk mucus permeability studies using the peptides cyclosporine A and vancomycin, ovalbumin as a model protein, as well as fluorescein-isothiocyanate dextrans (FDs) of different molecular weights and different surface charges were conducted in parallel to mucus retention force studies using a texture analyzer, rheological studies, cryo-scanning electron microscopy (cryo-SEM), and single particle tracking of fluorescence-labelled nanoparticles to investigate the effects of the SNAC-mucus interaction. The exposure of SNAC to PIM increased the mucus retention force, storage modulus, viscosity, increased nanoparticle confinement within PIM as well as decreased the permeation of cyclosporine A and ovalbumin through PIM. Surprisingly, the viscosity of PGM and the permeation of cyclosporine A and ovalbumin through PGM was unaffected by the presence of SNAC, thus the effect of SNAC depended on the regional site that mucus was collected from. In the absence of SNAC, the permeation of different molecular weight and differently charged FDs through PIM was comparable to that through BM. However, while bulk permeation of neither of the FDs through PIM was affected by SNAC, the presence of SNAC decreased the permeation of FD4 and increased the permeation of FD150 kDa through BM. Additionally, and in contrast to observations in PIM, nanoparticle confinement within BM remained unaffected by the presence of SNAC. In conclusion, the present study showed that SNAC altered the physical and barrier properties of PIM, but not of PGM. The effects of SNAC in PIM were not observed in the BM in vitro model. Altogether, the study highlights the need for further understanding how permeation enhancers influence the mucus barrier and illustrates that the selected mucus model for such studies should be chosen with care.

Can a humid storage environment of surgical instruments before reprocessing increase patient safety and durability of instruments?

BACKGROUND: National and international guidelines recommend reprocessing of medical instruments to commence as soon as possible post-surgery; furthermore, they recommend that transport and storage of surgical instruments postoperatively occurs in a moist, humid atmosphere. The concern is that a dry storage environment results in deterioration of instruments. AIM: To evaluate whether residual protein or corrosion is associated with storage environment (dry or humid), holding time or number of treatment cycles. METHODS: The range of protein residue and corrosion were tested on surgical instruments contaminated with human blood amended Enterococcus faecalis ATCC 29212. Subsequently instruments were stored for 6, 12 and 24 h in dry or humid conditions. After one, 25 and 50 reprocessing cycles, instruments were examined for protein residues using the o-phthaldialdehyde (OPA) method or corrosion using stereomicroscopy, scanning electron microscopy and energy dispersive spectroscopy. FINDINGS: Protein residue found on instruments was 21.5-54.0 µg and corrosion corresponded to 0-5% of the inspected area. No associations between storage environment and protein residue (adjusted mean difference = 0.48, 95% confidence interval: -0.42, 1.37, P=0.30) or corrosion (P=0.20) were identified. Higher numbers of treatment cycles showed higher amounts of corrosion (mean: 1cycle = 0.06%, 25cycles = 0.52% and 50cycles = 1.45%). In contrast, higher numbers of treatment cycles showed lower amounts of protein residue (P<0.001). We found both lower protein residue concentration and lower corrosion rating at 12 h compared with 6 and 24 h holding time. CONCLUSION: Cleanliness and durability of instruments before reprocessing seems not to be affected by storage environment or holding time but instead by number of treatment cycles.

Lateral ridge augmentation in the posterior part of the mandible with an autogenous bone block graft harvested from the ascending mandibular ramus. A 10-year retrospective study.

PURPOSE: The objective of the present retrospective study was to assess the long-term implant treatment outcome and patient satisfaction after lateral ridge augmentation in the posterior mandible with autogenous bone block graft harvested from the ascending mandibular ramus. MATERIALS AND METHODS: Seventy-four lateral ridge augmentation procedures in the posterior mandible with an autogenous bone block graft harvested from the ascending mandibular ramus and delayed placement of 87 implants was conducted in 46 consecutive patients from 2002-2006. Records and radiographs were retrospectively analyzed. Twenty-four patients responded to a 10-years follow-up examination including 39 lateral ridge augmentation procedures and 48 implants. Survival of suprastructures and implants, peri-implant marginal bone loss, patient perception and professional evaluation of the final implant treatment was assessed after 10 years. RESULTS: The 10-year survival of suprastructures and implants was 100% as all the implants and suprastructures were present with limited peri-implant marginal bone loss. The patients were highly satisfied with the esthetic and implant treatment outcome. CONCLUSION: Lateral ridge augmentation in the posterior mandible with autogenous bone block graft from the ascending mandibular ramus is characterized by high long-term implant survival rate and patient satisfaction.

Sandwich osteotomy of the atrophic posterior mandible with interpositional autogenous bone block graft compared with bone substitute material: a systematic review and meta-analysis.

The objective of the present systematic review was to test the hypothesis that there were no differences in outcome of implant treatment after sandwich osteotomy in the atrophic posterior mandible with interpositional autogenous bone block graft, compared with bone substitute material. A MEDLINE/PubMed, Embase and Cochrane Library search in combination with hand-search of selected journals was conducted. Two short-term randomised controlled trials with a split-mouth study design and low risk of bias fulfilled the inclusion criteria. High survival rate of suprastructures and implants was disclosed with no significant difference between interpositional autogenous bone block graft compared with bone substitute material. Meta-analysis revealed patient-based implant survival risk ratio of 1.05 (95% CI: 0.88 to 1.25) and peri-implant marginal bone loss of 0.31mm (95% CI: -0.29 to 0.90) indicating no significant differences between the two treatments. High implant stability values, gain in vertical alveolar ridge height, bone formation, and few complications were reported with both treatments. Sandwich osteotomy with interpositional grafting material appears to be a predictable surgical technique for enhancement of the vertical alveolar ridge height in the atrophic posterior mandible prior to implant placement.

EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide.

Membrane-active peptides have been extensively studied to probe protein-membrane interactions, to act as antimicrobial agents and cell-penetrating peptides (CPPs) for the delivery of therapeutic agents to cells. Hundreds of membrane-active sequences acting as CPPs have now been described including bioportides that serve as single entity modifiers of cell physiology at the intracellular level. Translation of promising CPPs in pre-clinical studies have, however, been disappointing as only few identified delivery systems have progressed to clinical trials. To search for novel membrane-active peptides a sequence from the EGFR juxtamembrane region was identified (named EJP18), synthesised, and examined in its L- and D-form for its ability to mediate the delivery of a small fluorophore and whole proteins to cancer cell lines. Initial studies identified the peptide as being highly membrane-active causing extensive and rapid plasma membrane reorganisation, blebbing, and toxicity. At lower, non-toxic concentrations the peptides outperformed the well-characterised CPP octaarginine in cellular delivery capacity for a fluorophore or proteins that were associated with the peptide covalently or via ionic interactions. EJP18 thus represents a novel membrane-active peptide that may be used as a naturally derived model for biophysical protein-membrane interactions or for delivery of cargo into cells for therapeutic or diagnostic applications.

Short implants (≤8mm) compared to standard length implants (>8mm) in conjunction with maxillary sinus floor augmentation: a systematic review and meta-analysis.

The objective was to test the hypothesis of no difference in the treatment outcome after the installation of short implants (≤8mm) in the posterior part of the maxilla compared to standard length implants (>8mm) in conjunction with maxillary sinus floor augmentation (MSFA) using the lateral window technique, after an observation period of ≥3years. A search of the MEDLINE, Embase, and Cochrane Library databases, in combination with a hand-search of relevant journals, was conducted. The search yielded 1102 titles. Finally, three studies that fulfilled the inclusion criteria were included. All were considered to have a low risk of bias. Meta-analyses revealed no significant differences in implant survival or peri-implant marginal bone loss between the two treatment modalities. However, the use of standard length implants in conjunction with MSFA was characterized by a tendency towards more peri-implant marginal bone loss. There was no statistically significant difference between the two treatment modalities with regard to overall patient satisfaction. Short implants seem to be a suitable alternative to standard length implants in conjunction with MSFA. However, further randomized controlled trials with larger patient samples and an observation period of more than 3years are needed before one treatment modality might be considered superior to the other.

Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing.

BACKGROUND: Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified. METHODS: Fresh-frozen tissue from primary tumours, synchronous liver metastases and adjacent normal liver was collected from 21 patients and analysed by whole-exome sequencing on the Illumina HiSeq 2500 platform. Gene variants designated as 'damaging' or 'potentially damaging' by Ingenuity software were used for the subsequent comparative analysis. BAM files were used as the input for the analysis of CNAs using NEXUS software. RESULTS: Shared mutations between the primary tumours and the synchronous liver metastases varied from 50 to 96%. Mutations in APC, KRAS, NRAS, TP53 or BRAF were concordant between the primary tumours and the metastases. Among the private mutations were well-known driver genes such as PIK3CA and SMAD4. The number of mutations was significantly higher in patients with right- compared to left-sided tumours (102 vs. 66, p = 0.004). Furthermore, right- compared to left-sided tumours had a significantly higher frequency of private mutations (p = 0.023). Similarly, CNAs differed between the primary tumours and the metastases. The difference was mostly comprised of numerical and segmental aberrations. However, novel CNAs were rarely observed in specific CRC-relevant genes. CONCLUSION: The examined primary colorectal tumours and synchronous liver metastases had multiple private mutations, indicating a high degree of inter-tumour heterogeneity in the individual patient. Moreover, the acquirement of novel CNAs from primary tumours to metastases substantiates the need for genomic profiling of metastases in order to tailor metastatic CRC therapies. As for the mutational status of the KRAS, NRAS and BRAF genes, no discordance was observed between the primary tumours and the metastases.

Administration of platelets to ruptured abdominal aortic aneurysm patients before open surgery: a prospective, single-blinded, randomised study.

BACKGROUND: In patients undergoing open surgery for a ruptured abdominal aortic aneurysm (rAAA), survivors demonstrate a high platelet count, and proactive administration of platelets (and fresh frozen plasma) appears to influence mortality. OBJECTIVES: This trial investigated the effect of platelets administered before transport to surgery. METHODS: In a prospective study design, patients were randomised to receive platelets (intervention; n = 61) or no platelets (control; n = 61) before transport to vascular surgery from 11 local hospitals. The study was terminated when one of the vascular surgical centres implemented endovascular repair for rAAA patients. RESULTS: Thirty days after surgery, mortality was 36% for patients with intervention vs 31% for controls (P = 0·32). Post-operative thrombotic events (14 vs 15; P = 0·69), renal failure (11 vs 10; P = 0·15) and pulmonary insufficiency (34 vs 39; P = 0·15) were similar in the two groups of patients. No adverse reactions to platelet administration were observed. In addition, length of stay in the intensive care unit was unaffected by intervention. CONCLUSIONS: For patients planned for open repair of a rAAA, we observed no significant effect of early administration of platelets with regard to post-operative complications and stay in the ICU or in hospital and also no significant effect on mortality.

Cerebral oximetry during preoperative resuscitation in elderly patients with hip fracture: a prospective observational study.

This study explores the association between postadmission and intraoperative cerebral oxygenation (ScO2), reflecting systemic perfusion, and postoperative mortality and delirium. Forty elderly (age > 65 years) patients with hip fractures were included in this prospective observational study. The ScO2 was determined using near-infrared spectroscopy at initial resuscitation after patients were admitted to the hospital and during surgery. Postoperative delirium was assessed up to seven days after surgery using the memorial delirium assessment scale and the confusion assessment method. Ten patients (25%) developed postoperative delirium within the first seven postoperative days. At initial resuscitation ScO2 was lower in patients that later developed delirium, but the difference was not significant (p = 0.331). Intraoperative ScO2 values remained similar in the two groups. Mortality regardless of cause was 10% (4 out of 40 patients) after 30 days. At initial resuscitation ScO2 was significant lower in the mortality group than in the surviving group (p = 0.042), and the ScO2 nadir values were also significant lower (p = 0.047). Low ScO2 during initial resuscitation (defined as ScO2 < 55 for a minimum of two consecutive minutes) was also significantly associated with 30-day mortality (p = 0.015). There were no associations between low blood pressure and postoperative delirium or 30-day mortality. We found that low preoperative ScO2 was better associated with 30-day all-cause mortality in elderly patients undergoing surgery for hip fracture than blood pressure measurements. Future studies in preoperative resuscitation of hip fracture patients should focus on perfusion measures as opposed to conventional haemodynamic.

Early-onset type 2 diabetes: Age gradient in clinical and behavioural risk factors in 5115 persons with newly diagnosed type 2 diabetes-Results from the DD2 study.

AIM: To examine the association between early onset of type 2 diabetes mellitus (DM) and clinical and behavioural risk factors for later complications of diabetes. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early onset) with diagnosis age 46 to 55, 56 to 65 (average onset = reference), 66 to 75, and >75 years (late onset). Prevalence ratios (PRs) were computed by using Poisson regression. RESULTS: Poor glucose control, ie, HbA1c ≥ 75 mmol/mol (≥9.0%) in the early-, average-, and late-onset groups was observed in 12%, 7%, and 1%, respectively (PR 1.70 [95% confidence intervals (CI) 1.27, 2.28] and PR 0.17 [95% CI 0.06, 0.45]). A similar age gradient was observed for severe obesity (body mass index > 40 kg/m2 : 19% vs. 8% vs. 2%; PR 2.41 [95% CI 1.83, 3.18] and 0.21 (95% CI 0.08, 0.57]), dyslipidemia (90% vs. 79% vs. 68%; PR 1.14 [95% CI 1.10, 1.19] and 0.86 [95% CI 0.79, 0.93]), and low-grade inflammation (C-reactive protein > 3.0 mg/L: 53% vs. 38% vs. 26%; PR 1.41 [95% CI 1.12, 1.78] and 0.68 [95% CI 0.42, 1.11]). Daily smoking was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2 DM need clinical awareness and support.

Low vs. high haemoglobin trigger for transfusion in vascular surgery: protocol for a randomised trial.

BACKGROUND: In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger-level lower than by guidelines from The European Society for Vascular Surgery. Restricting RBC transfusion may affect blood O2 transport with a risk for development of tissue ischaemia and postoperative complications. METHODS: In a single-centre, open-label, assessor blinded trial, 58 vascular surgical patients (> 40 years of age) awaiting open surgery of the infrarenal aorta or infrainguinal arterial bypass surgery undergo a web-based randomisation to one of two groups: perioperative RBC transfusion triggered by hb < 8 g/dl or hb < 9.7 g/dl. Administration of fluid follows an individualised strategy by optimising cardiac stroke volume and near-infrared spectroscopy determines tissue oxygenation. Serious adverse event rates are: myocardial injury (troponin-I ≥ 45 ng/l or ischaemic electrocardiographic findings at day 30), acute kidney injury, death, stroke and severe transfusion reactions. A follow-up visit takes place 30 days after surgery and a follow-up of serious adverse events in the Danish National Patient Register within 90 days is pending. DISCUSSION: This trial is expected to determine whether a RBC transfusion triggered by hb < 9.7 g/dl compared with hb < 8 g/dl results in adequate separation of postoperative hb levels, transfusion of more RBC units and maintains a higher tissue oxygenation. The results will inform the design of a multicentre trial for evaluation of important postoperative outcomes.

Novel genes involved in pathophysiology of gonadotropin-dependent adrenal tumors in mice.

Specific inbred strains and transgenic inhibin-α Simian Virus 40 T antigen (inhα/Tag) mice are genetically susceptible to gonadectomy-induced adrenocortical neoplasias. We identified altered gene expression in prepubertally gonadectomized (GDX) inhα/Tag and wild-type (WT) mice. Besides earlier reported Gata4 and Lhcgr, we found up-regulated Esr1, Prlr-rs1, and down-regulated Grb10, Mmp24, Sgcd, Rerg, Gnas, Nfatc2, Gnrhr, Igf2 in inhα/Tag adrenal tumors. Sex-steroidogenic enzyme genes expression (Srd5a1, Cyp19a1) was up-regulated in tumors, but adrenal-specific steroidogenic enzyme (Cyp21a1, Cyp11b1, Cyp11b2) down-regulated. We localized novel Lhcgr transcripts in adrenal cortex parenchyma and in non-steroidogenic A cells, in GDX WT and in intact WT mice. We identified up-regulated Esr1 as a potential novel biomarker of gonadectomy-induced adrenocortical tumors in inhα/Tag mice presenting with an inverted adrenal-to-gonadal steroidogenic gene expression profile. A putative normal adrenal remodeling or tumor suppressor role of the down-regulated genes (e.g. Grb10, Rerg, Gnas, and Nfatc2) in the tumors remains to be addressed.

Postoperative volume balance: does stroke volume increase in Trendelenburg's position?

In healthy humans, stroke volume (SV) and cardiac output (CO) do not increase with expansion of the central blood volume by head-down tilt or administration of fluid. Here, we exposed 85 patients to Trendelenburg's position about one hour after surgery while cardiovascular variables were determined non-invasively by Modelflow. In Trendelenburg's position, SV (83 ± 19 versus 89 ± 20 ml) and CO (6·2 ± 1·8 versus 6·8 ± 1·8 l/min; both P<0·05) increased, while heart rate (75 ± 15 versus 76 ± 14 b min-1 ) and mean arterial pressure were unaffected (84 ± 15 versus 84 ± 16 mmHg). For the 33 patients (39%) with a > 10% increase in SV (from 78 ± 16 to 90 ± 17 ml) corresponding to an increase in CO from 5·9 ± 1·5 to 6·9 ± 1·6 l min-1 (P<0·05) when tilted head-down, administration of 250 ml Ringer's lactate solution increased SV (to 88 ± 18 ml) and CO (to 6·8 ± 1·7 l min-1 ). In conclusion, determination of SV and/or CO in Trendelenburg's position can be used to evaluate whether a patient is in need of IV fluid as here exemplified after surgery.

Gender differences in the outcome of community-acquired Staphylococcus aureus bacteraemia: a historical population-based cohort study.

OBJECTIVES: Female gender has been suggested to be associated with poor outcome in patients with Staphylococcus aureus bacteraemia (SAB), but existing data remain sparse and conflicting. We investigated clinical outcomes in female and male patients with community-acquired (CA-) SAB. METHODS: Population-based medical registers were used to conduct a cohort study of all adult patients with CA-SAB in northern Denmark, 2000-2011. Thirty-day mortality after CA-SAB for female and male patients was estimated by the Kaplan-Meier method. Using Cox proportional hazards regression, we computed hazard ratios (HRs) of death according to gender, overall and stratified by age groups, co-morbidity level, and selected major diseases while adjusting for potential confounders. Moreover, we estimated 30-day prevalence proportions for SAB-associated infective endocarditis and osteomyelitis by gender. RESULTS: Among 2638 patients with CA-SAB, 1022 (39%) were female. Thirty-day mortality was 29% (n = 297) in female patients and 22% (n = 355) in male patients, yielding an adjusted HR (aHR) of 1.30 (95% CI, 1.11-1.53). This association appeared robust across age groups, whereas no consistent pattern was observed according to co-morbidity level. Compared with male patients, the prognostic impact of gender was most pronounced among female patients with diabetes (aHR 1.52; 95% CI 1.04-2.21)), and among female patients with cancer (aHR 1.40; 95% CI 1.04-1.90). The 30-day prevalence of infective endocarditis or osteomyelitis did not differ according to gender. CONCLUSION: Female patients with CA-SAB experienced increased 30-day mortality compared with male patients. Gender should be considered in the triage and risk stratification of CA-SAB patients.

The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia.

Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs) may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs), erythrocytes (ErytMVs), monocytes (MMVs), and endothelial cells (EMVs), as well as tissue factor-positive cells (TF+ MVs), were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation.

Near-infrared spectroscopy assessed cerebral oxygenation during open abdominal aortic aneurysm repair: relation to end-tidal CO2 tension.

During open abdominal aortic aneurism (AAA) repair cerebral blood flow is challenged. Clamping of the aorta may lead to unintended hyperventilation as metabolism is reduced by perfusion of a smaller part of the body and reperfusion of the aorta releases vasodilatory substances including CO2. We intend to adjust ventilation according end-tidal CO2 tension (EtCO2) and here evaluated to what extent that strategy maintains frontal lobe oxygenation (ScO2) as determined by near infrared spectroscopy. For 44 patients [5 women, aged 70 (48-83) years] ScO2, mean arterial pressure (MAP), EtCO2, and ventilation were obtained retrospectively from the anesthetic charts. By clamping the aorta, ScO2 and EtCO2 were kept stable by reducing ventilation (median, -0.8 l min(-1); interquartile range, -1.1 to -0.4; P < 0.001). During reperfusion of the aorta a reduction in MAP by 8 mmHg (-15 to -1; P < 0.001) did not prevent an increase in ScO2 by 2 % (-1 to 4; P < 0.001) as EtCO2 increased 0.5 kPa (0.1-1.0; P < 0.001) despite an increase in ventilation by 1.8 l min(-1) (0.9-2.7; P < 0.001). Changes in ScO2 related to those in EtCO2 (r = 0.41; P = 0.0001) and cerebral deoxygenation (-15 %) was noted in three patients while cerebral hyperoxygenation (+15 %) manifests in one patient. Thus changes in ScO2 were kept within acceptable limits (±15 %) in 91 % of the patients. For the majority of the patients undergoing AAA repair ScO2 was kept within reasonable limits by reducing ventilation by approximately 1 l min(-1) upon clamping of the aorta and increasing ventilation by approximately 2 l min(-1) when the lower body is reperfused.