Comparative in vitro activity of Meropenem, Imipenem and Piperacillin/tazobactam against 1071 clinical isolates using 2 different methods: a French multicentre study

<p>Abstract</p> <p>Background</p> <p>Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The major objective of the present study was to assess the <it>in vitro </it>activity of meropenem compared to imipenem and piperacillin/tazobactam, against 1071 non-repetitive isolates collected from patients with bacteremia (55%), pneumonia (29%), peritonitis (12%) and wound infections (3%), in 15 French hospitals in 2006. The secondary aim of the study was to compare the results of routinely testings and those obtained by a referent laboratory.</p> <p>Method</p> <p>Susceptibility testing and Minimum Inhibitory Concentrations (MICs) of meropenem, imipenem and piperacillin/tazobactam were determined locally by Etest method. Susceptibility to meropenem was confirmed at a central laboratory by disc diffusion method and MICs determined by agar dilution method for meropenem, imipenem and piperacillin/tazobactam.</p> <p>Results</p> <p>Cumulative susceptibility rates against <it>Escherichia coli </it>were, meropenem and imipenem: 100% and piperacillin/tazobactam: 90%. Against other <it>Enterobacteriaceae</it>, the rates were meropenem: 99%, imipenem: 98% and piperacillin/tazobactam: 90%. All <it>Staphylococci</it>, <it>Streptococci </it>and anaerobes were susceptible to the three antibiotics. Against non fermeters, meropenem was active on 84-94% of the strains, imipenem on 84-98% of the strains and piperacillin/tazobactam on 90-100% of the strains.</p> <p>Conclusions</p> <p>Compared to imipenem, meropenem displays lower MICs against <it>Enterobacteriaceae</it>, <it>Escherichia coli </it>and <it>Pseudomonas aeruginosa</it>. Except for non fermenters, MICs90 of carbapenems were <4 mg/L. Piperacillin/tazobactam was less active against <it>Enterobacteriaceae </it>and <it>Acinetobacter </it>but not <it>P. aeruginosa</it>. Some discrepancies were noted between MICs determined by Etest accross centres and MICs determined by agar dilution method at the central laboratory. Discrepancies were more common for imipenem testing and more frequently related to a few centres. Overall MICs determined by Etest were in general higher (0.5 log to 1 log fold) than MICs by agar dilution.</p

The association between retraction of the torn rotator cuff and increasing expression of hypoxia inducible factor 1α and vascular endothelial growth factor expression: an immunohistological study

<p>Abstract</p> <p>Background</p> <p>Differing levels of tendon retraction are found in full-thickness rotator cuff tears. The pathophysiology of tendon degeneration and retraction is unclear. Neoangiogenesis in tendon parenchyma indicates degeneration. Hypoxia inducible factor 1α (HIF) and vascular endothelial growth factor (VEGF) are important inducers of neoangiogenesis. Rotator cuff tendons rupture leads to fatty muscle infiltration (FI) and muscle atrophy (MA). The aim of this study is to clarify the relationship between HIF and VEGF expression, neoangiogenesis, FI, and MA in tendon retraction found in full-thickness rotator cuff tears.</p> <p>Methods</p> <p>Rotator cuff tendon samples of 33 patients with full-thickness medium-sized rotator cuff tears were harvested during reconstructive surgery. The samples were dehydrated and paraffin embedded. For immunohistological determination of VEGF and HIF expression, sample slices were strained with VEGF and HIF antibody dilution. Vessel density and vessel size were determined after Masson-Goldner staining of sample slices. The extent of tendon retraction was determined intraoperatively according to Patte's classification. Patients were assigned to 4 categories based upon Patte tendon retraction grade, including one control group. FI and MA were measured on standardized preoperative shoulder MRI.</p> <p>Results</p> <p>HIF and VEGF expression, FI, and MA were significantly higher in torn cuff samples compared with healthy tissue (p < 0.05). HIF and VEGF expression, and vessel density significantly increased with extent of tendon retraction (p < 0.05). A correlation between HIF/VEGF expression and FI and MA could be found (p < 0.05). There was no significant correlation between HIF/VEGF expression and neovascularity (p > 0.05)</p> <p>Conclusion</p> <p>Tendon retraction in full-thickness medium-sized rotator cuff tears is characterized by neovascularity, increased VEGF/HIF expression, FI, and MA. VEGF expression and neovascularity may be effective monitoring tools to assess tendon degeneration.</p

Description of an aerodynamic levitation apparatus with applications in Earth sciences

<p>Abstract</p> <p>Background</p> <p>In aerodynamic levitation, solids and liquids are floated in a vertical gas stream. In combination with CO₂-laser heating, containerless melting at high temperature of oxides and silicates is possible. We apply aerodynamic levitation to bulk rocks in preparation for microchemical analyses, and for evaporation and reduction experiments.</p> <p>Results</p> <p>Liquid silicate droplets (~2 mm) were maintained stable in levitation using a nozzle with a 0.8 mm bore and an opening angle of 60°. The gas flow was ~250 ml min^-1. Rock powders were melted and homogenized for microchemcial analyses. Laser melting produced chemically homogeneous glass spheres. Only highly (e.g. H₂O) and moderately volatile components (Na, K) were partially lost. The composition of evaporated materials was determined by directly combining levitation and inductively coupled plasma mass spectrometry. It is shown that the evaporated material is composed of Na > K >> Si. Levitation of metal oxide-rich material in a mixture of H₂and Ar resulted in the exsolution of liquid metal.</p> <p>Conclusions</p> <p>Levitation melting is a rapid technique or for the preparation of bulk rock powders for major, minor and trace element analysis. With exception of moderately volatile elements Na and K, bulk rock analyses can be performed with an uncertainty of ± 5% relative. The technique has great potential for the quantitative determination of evaporated materials from silicate melts. Reduction of oxides to metal is a means for the extraction and analysis of siderophile elements from silicates and can be used to better understand the origin of chondritic metal.</p

Comparison of quality-of-care measures in U.S. patients with end-stage renal disease secondary to lupus nephritis vs. other causes

BACKGROUND: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN-ESRD) may be followed by multiple providers (nephrologists and rheumatologists) and have greater opportunities to receive recommended ESRD-related care. We aimed to examine whether LN-ESRD patients have better quality of ESRD care compared to other ESRD patients. METHODS: Among incident patients (7/05–9/11) with ESRD due to LN (n = 6,594) vs. other causes (n = 617,758), identified using a national surveillance cohort (United States Renal Data System), we determined the association between attributed cause of ESRD and quality-of-care measures (pre-ESRD nephrology care, placement on the deceased donor kidney transplant waitlist, and placement of permanent vascular access). Multivariable logistic and Cox proportional hazards models were used to estimate adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: LN-ESRD patients were more likely than other ESRD patients to receive pre-ESRD care (71% vs. 66%; OR = 1.68, 95% CI 1.57-1.78) and be placed on the transplant waitlist in the first year (206 vs. 86 per 1000 patient-years; HR = 1.42, 95% CI 1.34–1.52). However, only 24% had a permanent vascular access (fistula or graft) in place at dialysis start (vs. 36%; OR = 0.63, 95% CI 0.59–0.67). CONCLUSIONS: LN-ESRD patients are more likely to receive pre-ESRD care and have better access to transplant, but are less likely to have a permanent vascular access for dialysis, than other ESRD patients. Further studies are warranted to examine barriers to permanent vascular access placement, as well as morbidity and mortality associated with temporary access, in patients with LN-ESRD

Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosclerosis have been described. Though the immunosuppression used for each of the transplant types, cardiac, liver and HSCT is similar, the risk factors for developing CKD and the CKD severity described in patients after transplant vary. As the indications for transplant and the long-term survival improves for these children, so will the burden of CKD. Nephrologists should be involved early in the pretransplant workup of these patients. Transplant physicians and nephrologists will need to work together to identify those patients at risk of developing CKD early to prevent its development and progression to end-stage renal disease

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030