Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Cochrane review: Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants

Abstract: Background Neonatal extracorporeal membrane oxygenation (ECMO) is a complex procedure of life support used in severe but potentially reversible respiratory failure in term infants. Although the number of babies eligible for ECMO is small and the use of ECMO invasive and potentially expensive, its benefits may be high. Objectives To determine whether ECMO used for neonatal infants with severe respiratory failure is clinically and cost effective compared to conventional ventilatory support. Search strategy The Cochrane Neonatal Group Specialised Register, the Cochrane Controlled Trials Register, and MEDLINE were searched for 1974 to 2007. Selection criteria All randomised trials comparing neonatal ECMO to conventional ventilatory support. Data collection and analysis The authors independently evaluated the trials for methodological quality and appropriateness for inclusion in the Review (without consideration of their results) and independently extracted the data. Main results The four trials (three USA and one UK) recruited clinically similar groups of babies. Two trials excluded infants with congenital diaphragmatic hernias. In two trials, transfer for ECMO implied transport over long distances. Two trials had follow-up information. One study included economic evaluation. The three USA trials had very small numbers of patients. Two trials used conventional randomisation with low potential for bias. Two used less usual designs, which led to difficulties in their interpretation. All four trials showed strong benefit of ECMO on mortality (typical RR 0.44; 95% CI 0.31 to 0.61), especially for babies without congenital diaphragmatic hernia (typical RR 0.33, 95% CI 0.21 to 0.53). The UK trial provided follow up information about death or severe disability, and cost-effectiveness, and showed benefit of ECMO at one year (RR 0.56, 95% CI 0.40 to 0.78), four years (RR 0.62, 95% CI 0.45 to 0.86), and seven years (RR 0.64, 95% CI 0.47 to 0.86). Overall nearly half of the children recruited had died or were severely disabled by seven years of age, reflecting the severity of their underlying conditions. A policy of ECMO is as cost-effective as other intensive care technologies in common use. Authors' conclusions A policy of using ECMO in mature infants with severe but potentially reversible respiratory failure results in significantly improved survival without increased risk of severe disability. The benefit of ECMO for babies with diaphragmatic hernia is unclear. Further studies are needed to consider the optimal timing for introducing ECMO; to identify which infants are most likely to benefit; and to address the implications of neonatal ECMO during later childhood and adult life. Plain Language Summary Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants A complex life support procedure, called extracorporeal membrane oxygenation (ECMO), can be used in infants who are near term age to overcome severe, potentially reversible breathing problems. ECMO is similar to the technology used in cardiac bypass surgery. Blood is removed from the body of the patient, oxygen is added to the blood, and the blood is returned to the patient. Although the number of babies requiring ECMO is small, and ECMO is a very invasive and potentially expensive procedure, the benefits of this procedure are high. In this review, four randomized trials that compared the use of ECMO to the conventional approach to supporting these infants with severe breathing problems were identified. Overall, these trials showed a strong benefit for ECMO regarding survival at the time of hospital discharge. This is particularly true for infants without a specific problem of lung formation (congenital diaphragmatic hernia). The result implies that for every three babies with breathing problems and lung failure who were treated with ECMO rather than conventional ventilation, one more infant will survive. Although little information is available regarding long-term follow-up, one trial in the United Kingdom shows both benefits of ECMO and cost-effectiveness of the use of ECMO.

Conformational change and mitochondrial translocation of Bax accompany proteasome inhibitor-induced apoptosis of chronic lymphocytic leukemic cells.

Abstract: Chemotherapy resistance remains a major clinical problem in patients with B-cell chronic lymphocytic leukemia (B-CLL). Proteasome inhibitors are able to induce apoptosis in chemotherapy-resistant B-CLL cells in vitro. Exposure of B-CLL cells to the proteasome inhibitors, MG132 and lactacystin, resulted in inhibition of proteasomal activity within 30 min of treatment and was accompanied by an increase in the level of ubiquitinated proteins. Proteasome inhibitors did not alter the levels of expression of the proapoptotic Bcl-2 family proteins, Bax and Bid, prior to the onset of apoptosis. Instead, proteasome inhibitors induced a caspase-independent conformational change in Bax (as shown by a conformation-specific Bax antibody) and its translocation to mitochondria, resulting in mitochondrial perturbation, as evidenced by loss of the mitochondrial membrane potential and cytochrome c release. Similar conformational change and subcellular localization of Bax were observed during apoptosis induced with fludarabine, chlorambucil and prednisolone. These data suggest that alteration of Bax conformation and its redistribution to mitochondria are common and early features of B-CLL apoptosis in response to proteasome inhibitors and other chemotherapeutic agents.

Clinical outcome of primary infrainguinal subintimal angioplasty in diabetic patients with critical lower limb ischemia.

Abstract: Purpose:To evaluate the clinical outcome of subintimal angioplasty in diabetic patients with critical limb ischemia (CLI) compared to nondiabetics irrespective of the patency status of the treated ...

Outcome of traumatic subtrochanteric femoral fractures fixed using cephalo-medullary nails.

Abstract: We performed a retrospective review of 101 patients sustaining 102 traumatic, non-pathological subtrochanteric fractures treated with cephalo-medullary nailing over a period of 6 years from 1999 to 2005. Mean follow up was 24 weeks (range: 6-96). Twenty patients were lost to follow up and 21 died, whilst 57 of 60 fractures were followed to union. There were 19 fractures fixed in varus, as defined as a varus angulation of greater than 10 degrees at the fracture site. Implant failure, 9 of the 10 malunions and all 3 of the non-unions occurred in the varus group whilst only 1 malunion occurred in the satisfactory reduction group. This difference in outcome is statistically significant (p 0.05). Post-operative recovery rates, infection rates and other complications were similar for both groups. We therefore advocate the use of open reduction where necessary to avoid varus malreduction to avoid such complications, particularly as open reduction was not associated with a higher complication rate in this series. The study supports the use of cephalo-medullary nailing for subtrochanteric fractures with a union rate of 95%.