[The AO/ASIF Flexnail : A flexible intramedullary nail for the treatment of humeral shaft fractures]

BACKGROUND: The use of conventional implants for intramedullary nailing of humeral shaft fractures is associated with specific difficulties. During antegrade implantation structures of the rotator cuff can be affected leading to a reduced functional result of the shoulder. If the nail is implanted in a retrograde manner problems arise due to a relatively large hole close to or within the olecranon fossa, which is necessary for insertion of the nail. Supracondylar fractures as well as persistent elbow pain and loss of function are reported in the literature. To overcome these disadvantages a flexible nail has been developed that can be stiffened and locked after implantation. METHOD: Between October 2000 and February 2002, 34 patients were treated with the flexible nail at our institution; 29 were available for follow-up. Fracture healing was documented on radiographs and clinical outcome was evaluated with use of the Constant as well as the Kwasny score. RESULTS: Median duration until fracture consolidation was 10 weeks. In two patients fracture union was not achieved within the follow-up period. The median outcome measured with the Constant score was 93 points and 2.5 with the Kwasny score. Both values correspond to a very good functional outcome. CONCLUSION: We conclude that the flexible humeral nail is an excellent treatment option for humeral shaft fractures. Damage to the rotator cuff and the distal humerus can be avoided due to its unique flexible construction, improving the functional outcome of intramedullary nailing for the treatment of humeral shaft fractures.

The "flap-shaft" prosthesis for insensate feet with Chopart or Lisfranc amputations

BACKGROUND: The inevitable detachment of tendons and the loss of the forefoot in Chopart and Lisfranc amputations result in equinus and varus of the residual foot. In an insensate foot these deformities can lead to keratotic lesions and ulcerations. The currently available prostheses cannot safely counteract the deforming forces and the resulting complications. METHODS: A new below-knee prosthesis was developed, combining a soft socket with a rigid shaft. The mold is taken with the foot in the corrected position. After manufacturing the shaft, the lateral third of the circumference of the shaft is cut away and reattached distally with a hinge, creating a lateral flap. By closing this flap the hindfoot is gently levered from the varus position into valgus. Ten patients (seven amputations at the Chopart-level, three amputations at the Lisfranc-level) with insensate feet were fitted with this prosthesis at an average of 3 (range 1.5 to 9) months after amputation. The handling, comfort, time of daily use, mobility, correction of malposition and complications were recorded to the latest followup (average 31 months, range 24 to 37 months after amputation). RESULTS: Eight patients evaluated the handling as easy, two as difficult. No patient felt discomfort in the prosthesis. The average time of daily use was 12 hours, and all patients were able to walk. All varus deformities were corrected in the prosthesis. Sagittal alignment was kept neutral. Complications were two minor skin lesions and one small ulcer, all of which responded to conservative treatment, and one ulcer healed after debridement and lengthening of the Achilles tendon. CONCLUSIONS: The "flap-shaft" prosthesis is a valuable option for primary or secondary prosthetic fitting of Chopart-level and Lisfranc-level amputees with insensate feet and flexible equinus and varus deformity at risk for recurrent ulceration. It provided safe and sufficient correction of malpositions and enabled the patients to walk as much as their general condition permitted.

rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants

BACKGROUND: The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. METHODS: Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C). RESULTS: All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. CONCLUSION: IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.

Elective implantation of sirolimus-eluting stents for bifurcated and non-bifurcated unprotected left main coronary artery lesions: clinical outcomes at one year

AIMS: Recent studies of drug-eluting stents for unprotected left main coronary artery (LMCA) disease have been encouraging. We examined the performance of sirolimus-eluting stents (SES) for this indication. METHODS AND RESULTS: This retrospective study included 228 consecutive patients (mean age = 68 +/- 11 years, 80.6% men, 26.3% diabetics) who underwent implantation of SES for de novo LMCA stenoses. The mean additive and logistic EuroSCOREs were 5.2 +/- 3.9 and 8.2 +/- 13.2, respectively. The main objective of this study was to measure the rate of major adverse cardiac events (MACE), including death, myocardial infarction and target lesion revascularisation (TLR) at 12 months. Other objectives were to measure the rates of in-hospital MACE and 12-month TLR. Outcomes in 143 patients with (BIF+ group), versus 84 patients without (BIF-group) involvement of the bifurcation were compared. The pre-procedural percent diameter stenosis (%DS) was 60.1 +/- 11.2 in the BIF+ versus 54.7 +/- 12.2% in the BIF- group (p=0.008), and decreased to 18.0 +/- 9.7 and 13.9 +/- 11.3%, respectively (ns), after SES implant. The overall in-hospital MACE rate was 3.5%, and similar in both subgroups. The 1-year MACE rate was 14.5% overall, 16.8% in the BIF+ and 10.7% in the BIF- subgroup (ns). CONCLUSIONS: SES implants in high-risk patients with LMCA stenoses were associated with a low 1-year MACE rate. Stenting of the bifurcation was associated with significant increases in neither mortality nor 1-year MACE rate.

Longest available clinical outcomes after drug-eluting stent implantation for unprotected left main coronary artery disease: the DELFT (Drug Eluting stent for LeFT main) Registry

OBJECTIVES: The purpose of this study was to investigate the long-term safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for unprotected left main coronary artery (ULMCA) disease. BACKGROUND: Long-term clinical outcomes after DES implantation for ULMCA disease have not yet been ascertained. METHODS: From April 2002 to April 2004, 358 consecutive patients who underwent PCI with DES implantation for de novo lesions on ULMCA were retrospectively selected and analyzed in 7 European and U.S. tertiary care centers. No patients were excluded from the analysis, and all patients had a minimum follow-up of 3 years. RESULTS: Technical success rate was 100%. Procedural success rate was 89.6%. After 3 years, major adverse cardiovascular events (MACE)-free survival in the whole population was 73.5%. According to the Academic Research Consortium definitions, cardiac death occurred in 9.2% of patients, and reinfarction, target lesion revascularization (TLR), and target vessel revascularization (TVR) occurred in 8.6%, 5.8%, and 14.2% of patients, respectively. Definite stent thrombosis occurred in 2 patients (specifically at 0 and 439 days). In elective patients, the 3-year MACE-free survival was 74.2%, with mortality, reinfarction, TLR, and TVR rates of 6.2%, 8.3%, 6.6%, and 16%, respectively. In the emergent group the 3-year MACE-free survival was 68.2%, with mortality, reinfarction, TLR, and TVR rates of 21.4%, 10%, 2.8%, and 7.1%, respectively. CONCLUSIONS: Routine DES implantation in ULMCA disease seems encouraging, with favorable long-term clinical results.

Diabetic patients treated for unprotected left main coronary artery disease with drug eluting stents: a 3-year clinical outcome study. The diabetes and drug eluting stent for LeFT main registry (D-DELFT)

AIMS: Diabetes mellitus (DM) plays an important role in the development of coronary artery disease. Although previous studies have associated drug-eluting stent (DES) implantation in diabetic patients with favourable clinical and angiographic outcomes, the very long-term efficacy of these devices in diabetic patients undergoing PCI for significant unprotected left main coronary artery (ULMCA) disease has not been established yet. METHODS AND RESULTS: Consecutive diabetic patients (n=100), who underwent elective PCI with DES for de novo lesions in an ULMCA between April 2002 and April 2004 in seven tertiary health care centres, were identified retrospectively and analysed. Consecutive non-diabetic patients (n=193), who underwent elective DES implantation for unprotected ULMCA disease, were selected as a control group. All patients were followed for at least 36 months. At 3-years follow-up, freedom from cardiac death ; myocardial infarction (CDMI), target lesion revascularisation (TLR) and target vessel revascularisation (TVR) did not differ significantly between groups. The adjusted freedom from major adverse cardiac events (MACE, defined as the occurrence of CD, MI or TVR) was 63.4% in the DM group and 77.6% in the controls (p<0.001). When divided into IDDM and NIDDM sub-groups, insulin-dependent DM (IDDM) but not non IDDM (NIDDM) patients had significantly lower freedom from CDMI, TLR, TVR and MACE compared to controls. CONCLUSIONS: These results suggest that major improvements in DES technology and pharmacotherapy are still required to improve clinical outcome and that the decision to perform percutaneous revascularisation in this subset of patients should be taken cautiously and on a case by case basis.

Reducing main memory access latency through SDRAM address mapping techniques and access reordering mechanisms

As the performance gap between microprocessors and memory continues to increase, main memory accesses result in long latencies which become a factor limiting system performance. Previous studies show that main memory access streams contain significant localities and SDRAM devices provide parallelism through multiple banks and channels. These locality and parallelism have not been exploited thoroughly by conventional memory controllers. In this thesis, SDRAM address mapping techniques and memory access reordering mechanisms are studied and applied to memory controller design with the goal of reducing observed main memory access latency. The proposed bit-reversal address mapping attempts to distribute main memory accesses evenly in the SDRAM address space to enable bank parallelism. As memory accesses to unique banks are interleaved, the access latencies are partially hidden and therefore reduced. With the consideration of cache conflict misses, bit-reversal address mapping is able to direct potential row conflicts to different banks, further improving the performance. The proposed burst scheduling is a novel access reordering mechanism, which creates bursts by clustering accesses directed to the same rows of the same banks. Subjected to a threshold, reads are allowed to preempt writes and qualified writes are piggybacked at the end of the bursts. A sophisticated access scheduler selects accesses based on priorities and interleaves accesses to maximize the SDRAM data bus utilization. Consequentially burst scheduling reduces row conflict rate, increasing and exploiting the available row locality. Using a revised SimpleScalar and M5 simulator, both techniques are evaluated and compared with existing academic and industrial solutions. With SPEC CPU2000 benchmarks, bit-reversal reduces the execution time by 14% on average over traditional page interleaving address mapping. Burst scheduling also achieves a 15% reduction in execution time over conventional bank in order scheduling. Working constructively together, bit-reversal and burst scheduling successfully achieve a 19% speedup across simulated benchmarks.

Polyarteritis Nodosa, a vanishing vasculitis since its main cause has been identified

The polyarteritis nodosa is a vasculitis for which the main cause had been identified as hepatitis B, a chronic infectious disease inducing an overshooting immune reaction. Thanks to this discovery, the treatment of polyarteritis nodosa has changed from a symptomatic immunosuppressive therapy to a treatment strategy focusing on the disease inducing infectious agent. Vaccination against hepatitis B- virus has been instrumental in the reduction of the prevalence of polyarteritis nodosa. In case of the rare entity of polyarteritis nodosa without hepatitis B, only a symptomatic immunosuppressive therapy can be prescribed. The history of polyarteritis nodosa clearly illustrates that future research in the field of so called autoimmune diseases should focus on the causes rather than on the immunologic effector mechanisms and/or the symptomatic immunosuppressive therapy.

Unprotected left main stenting in the real world: two-year outcomes of the French left main taxus registry

BACKGROUND: Cardiac surgery is the reference treatment for patients with left main (LM) disease, although percutaneous coronary intervention with drug-eluting stents is emerging as a possible alternative. The objective of this registry was to evaluate the 2-year outcome of elective percutaneous coronary intervention for unprotected LM disease with paclitaxel-eluting stents. METHODS AND RESULTS: A total of 291 patients were prospectively included from 4 centers. Acute myocardial infarction and cardiogenic shock were the only exclusion criteria. Patients were 69+/-11 years old, 29% were diabetic, and 25% had 3-vessel disease. For distal LM lesions (78%), the provisional side-branch T-stenting approach was used in 92% of cases and final kissing balloon inflation in 97%. Angiographic success was obtained in 99.7% of cases. At 2-year follow-up, the total cardiac death rate was 5.4% (1 EuroSCORE point was associated with a 15% [95% confidence interval 2.9% to 28.2%, P=0.013] higher risk of cardiac death), target-lesion revascularization was 8.7%, and incidence of Q-wave or non-Q-wave myocardial infarction was 0.9% and 3.1%, respectively. The combined end point occurred in 15.8% of cases and stroke in 0.7%. The incidence of definite and probable LM stent thrombosis was 0.7%, whereas the incidence of any stent thrombosis was 3.8%, with a higher risk in patients with side-branch stenting in the presence of LM bifurcation lesions (hazard ratio 9.6, 95% confidence interval 1.2 to 77.7, P=0.035). CONCLUSIONS: Unprotected LM stenting with paclitaxel-eluting stents, with a strategy of provisional side-branch T-stenting for distal lesions, provides excellent acute angiographic results and good mid-term clinical outcomes, with a 15.8% rate of major adverse cardiac events at 2-year follow-up.

The Single Mitochondrial Porin of Trypanosoma brucei is the Main Metabolite Transporter in the Outer Mitochondrial Membrane

All mitochondria have integral outer membrane proteins with beta-barrel structures including the conserved metabolite transporter VDAC (voltage dependent anion channel) and the conserved protein import channel Tom40. Bioinformatic searches of the Trypanosoma brucei genome for either VDAC or Tom40 identified a single open reading frame, with sequence analysis suggesting that VDACs and Tom40s are ancestrally related and should be grouped into the same protein family: the mitochondrial porins. The single T. brucei mitochondrial porin is essential only under growth conditions that depend on oxidative phosphorylation. Mitochondria isolated from homozygous knockout cells did not produce adenosine-triphosphate (ATP) in response to added substrates, but ATP production was restored by physical disruption of the outer membrane. These results demonstrate that the mitochondrial porin identified in T. brucei is the main metabolite channel in the outer membrane and therefore the functional orthologue of VDAC. No distinct Tom40 was identified in T. brucei. In addition to mitochondrial proteins, T. brucei imports all mitochondrial tRNAs from the cytosol. Isolated mitochondria from the VDAC knockout cells import tRNA as efficiently as wild-type. Thus, unlike the scenario in plants, VDAC is not required for mitochondrial tRNA import in T. brucei.