Treatment and Outcome of Osteoporotic Thoracolumbar Vertebral Fractures With Anterior or Posterior Tension Band Failure (OF 5): Short-Term Results From the Prospective EOFTT Multicenter Study.

STUDY DESIGN: Subgroup analysis of a multicenter prospective cohort study. OBJECTIVE: To analyse surgical strategies applied to osteoporotic thoracolumbar osteoporotic fracture (OF) 5 injuries with anterior or posterior tension band failure and to assess related complications and clinical outcome. METHODS: A multicenter prospective cohort study (EOFTT) was conducted at 17 spine centers including 518 consecutive patients who were treated for an osteoporotic vertebral fracture (OVF). For the present study, only patients with OF 5 fractures were analysed. Outcome parameters were complications, Visual Analogue Scale (VAS), Oswestry Disability Questionnaire (ODI), Timed Up & Go test (TUG), EQ-5D 5L, and Barthel Index. RESULTS: In total, 19 patients (78 ± 7 years, 13 female) were analysed. Operative treatment consisted of long-segment posterior instrumentation in 9 cases and short-segment posterior instrumentation in 10 cases. Pedicle screws were augmented in 68 %, augmentation of the fractured vertebra was performed in 42%, and additional anterior reconstruction was done in 21 %. Two patients (11 %) received short-segment posterior instrumentation without either anterior reconstruction or cement-augmentation of the fractured vertebra. No surgical or major complications occurred, but general postoperative complications were observed in 45%. At a follow-up of mean 20 ± 10 weeks (range, 12 to 48 weeks), patients showed significant improvements in all functional outcome parameters. CONCLUSIONS: In this analysis of patients with type OF 5 fractures, surgical stabilization was the treatment of choice and lead to significant short-term improvement in terms of functional outcome and quality of life despite a high general complication rate.

Georg Schmorl prize of the German spine society (DWG) 2022: current treatment for inpatients with osteoporotic thoracolumbar fractures-results of the EOFTT study.

AIM: Osteoporotic thoracolumbar fractures are of increasing importance. To identify the optimal treatment strategy this multicentre prospective cohort study was performed. PURPOSE: Patients suffering from osteoporotic thoracolumbar fractures were included. Excluded were tumour diseases, infections and limb fractures. Age, sex, trauma mechanism, OF classification, OF-score, treatment strategy, pain condition and mobilization were analysed. METHODS: A total of 518 patients' aged 75 ± 10 (41-97) years were included in 17 centre. A total of 174 patients were treated conservatively, and 344 were treated surgically, of whom 310 (90%) received minimally invasive treatment. An increase in the OF classification was associated with an increase in both the likelihood of surgery and the surgical invasiveness. RESULTS: Five (3%) complications occurred during conservative treatment, and 46 (13%) occurred in the surgically treated patients. 4 surgical site infections and 2 mechanical failures requested revision surgery. At discharge pain improved significantly from a visual analogue scale score of 7.7 (surgical) and 6.0 (conservative) to a score of 4 in both groups (p < 0.001). Over the course of treatment, mobility improved significantly (p = 0.001), with a significantly stronger (p = 0.007) improvement in the surgically treated patients. CONCLUSION: Fracture severity according to the OF classification is significantly correlated with higher surgery rates and higher invasiveness of surgery. The most commonly used surgical strategy was minimally invasive short-segmental hybrid stabilization followed by kyphoplasty/vertebroplasty. Despite the worse clinical conditions of the surgically treated patients both conservative and surgical treatment led to an improved pain situation and mobility during the inpatient stay to nearly the same level for both treatments.

A method for revision of a foreshortened transjugular intrahepatic portosystemic shunt (TIPS) stent using transhepatic trans-stent access.

The high technical success rate of transjugular intrahepatic portosystemic shunt (TIPS) placement makes the procedure a popular treatment option for symptomatic portal hypertension. Among the major drawbacks of the procedure - hepatic encephalopathy, acute hepatic failure, hemorrhage, biliary injury - TIPS dysfunction is one of the most prevalent, often requiring endovascular reintervention. Conventional techniques for shunt revision rely on transjugular access to the stent; but in technically difficult cases of abnormal angulation or severe stenosis, transhepatic access may also be required. The pull-through method utilizes both transjugular and transhepatic access to achieve stable through-and-through access in order to advance a sheath into the stent and recannulate the shunt. In the case of TIPS foreshortening, however, the distal end of the stent may abut the wall of the hepatic vein, jailing it off and obviating the advancement of a wire out of that end. We present here a case of a modified pull-through method for TIPS revision whereby a transhepatic wire is passed through the interstices of the stent at the distal end to enter into the hepatic vein and IVC. Subsequent snaring of the wire at the transjugular end establishes through-and-through access, and balloon dilation through the interstices allows for insertion of a transjugular sheath into the TIPS stent for recanalization. Our case highlights how the modified pull-through method, using trans-stent access, can be safely performed in patients with a foreshortened TIPS that abuts against the hepatic and portal vessel walls.

Engineering two species of yeast as cell factories for 2'-fucosyllactose.

Oligosaccharides present in human breast milk have been linked to beneficial effects on infant health. Inclusion of these human milk oligosaccharides (HMOs) in infant formula can recapitulate these health benefits. As a result, there is substantial commercial interest in a cost-effective source of HMOs as infant formula ingredients. Here we demonstrate that the yeast species Saccharomyces cerevisiae and Yarrowia lipolytica both can be engineered to produce 2'-fucosyllactose (2'FL), which is the most abundant oligosaccharide in human breast milk, at high titer and productivity. Both yeast species were modified to enable uptake of lactose and synthesis of GDP-fucose - the two precursors of 2'FL - by installing a lactose transporter and enzymes that convert GDP-mannose to GDP-fucose. Production of 2'FL was then enabled by expression of α-1,2-fucosyltransferases from various organisms. By screening candidate transporters from a variety of sources, we identified transporters capable of exporting 2'FL from yeast, which is a key consideration for any biocatalyst for 2'FL production. In particular, we identified CDT2 from Neurospora crassa as a promising target for further engineering to improve 2'FL efflux. Finally, we demonstrated production of 2'FL in fermenters at rates and titers that indicate the potential of engineered S. cerevisiae and Y. lipolytica strains for commercial 2'FL production.

Optimization of Polymyxin B in Combination with Doripenem To Combat Mutator Pseudomonas aeruginosa.

Development of spontaneous mutations in Pseudomonas aeruginosa has been associated with antibiotic failure, leading to high rates of morbidity and mortality. Our objective was to evaluate the pharmacodynamics of polymyxin B combinations against rapidly evolving P. aeruginosa mutator strains and to characterize the time course of bacterial killing and resistance via mechanism-based mathematical models. Polymyxin B or doripenem alone and in combination were evaluated against six P. aeruginosa strains: wild-type PAO1, mismatch repair (MMR)-deficient (mutS and mutL) strains, and 7,8-dihydro-8-oxo-deoxyguanosine system (GO) base excision repair (BER)-deficient (mutM, mutT, and mutY) strains over 48 h. Pharmacodynamic modeling was performed using S-ADAPT and facilitated by SADAPT-TRAN. Mutator strains displayed higher mutation frequencies than the wild type (>600-fold). Exposure to monotherapy was followed by regrowth, even at high polymyxin B concentrations of up to 16 mg/liter. Polymyxin B and doripenem combinations displayed enhanced killing activity against all strains where complete eradication was achieved for polymyxin B concentrations of >4 mg/liter and doripenem concentrations of 8 mg/liter. Modeling suggested that the proportion of preexisting polymyxin B-resistant subpopulations influenced the pharmacodynamic profiles for each strain uniquely (fraction of resistance values are -8.81 log10 for the wild type, -4.71 for the mutS mutant, and -7.40 log10 for the mutM mutant). Our findings provide insight into the optimization of polymyxin B and doripenem combinations against P. aeruginosa mutator strains.

Challenges for Restoration of Lower Urinary Tract Innervation in Patients with Spinal Cord Injury: A European Single-center Retrospective Study with Long-term Follow-up.

UNLABELLED: Xiao and colleagues in China reported successful restoration of bladder control in patients with spinal cord injury (SCI) by establishing a somatic-autonomic reflex pathway through lumbar-to-sacral ventral root nerve rerouting. We evaluated long-term results in eight patients who underwent this procedure at a German university clinic between 2005 and 2007. The primary outcome was the occurrence of voiding upon stimulation of the skin, with normalization of bladder pressure when filling, as assessed with videourodynamics at each visit. Videourodynamic variables, urinary tract infections, and bladder/stool events recorded in a patient diary were stored in a prospective database and reviewed retrospectively. Intraoperative testing indicated successful nerve rerouting in all eight patients. Duration of follow-up was 71 mo (range: 56-86). No patient reached the primary goal of voluntary voiding with normalization of detrusor pressure at any point during follow-up. No improvements in videourodynamic or diary variables regarding bladder function were observed. In view of the lack of short (12-18 mo) and long-term (71 mo) success in our patients and others, the risks of any surgical procedure using general anesthesia, and potential for unmet expectations to wreak havoc on patient emotional well-being, we cannot recommend this procedure for patients with SCI. PATIENT SUMMARY: Although the hope was to improve long-term outcomes of spinal cord injury patients, intraspinal nerve rerouting did not improve or normalize bladder function. In view of the lack of success, we cannot recommend this procedure until proven in clinical studies.

Melanization of flavonoids by fungal and bacterial laccases.

Laccase activity in plants results in the formation of a number of brown pigments, often referred to as tannins. Laccase-dependent pigment production is also catalogued in numerous fungal and bacterial species. The laccase of the haploid yeast Cryptococcus neoformans forms melanin-like pigmentation outside the cell wall in the presence of exogenous substrates. While this process is a contributing factor to its virulence in humans, the evolutionary intent for the laccase function remains a mystery. We show here that C. neoformans and Bacillus subtilis have the ability to create melanin-like pigments from a variety of flavonoid molecules across a range of conformations, preferring those with 3',4'-dihydroxylations. Since flavonoids are ubiquitous plant molecules and often-considered antimicrobial agents, we postulate that they are the intended natural targets of laccase activity and result in the formation of a defensive melanin-like coat. These results suggests a new mechanism by which flavonoid-melanin formation may occur, using not only A- and C-ring linkages, but also monomer links through the B-ring of the flavonoid structure. We also show that resveratrol and other non- and mono-hydroxylated polyphenol substrates have the ability to restrict pigment formation and may be potent inhibitors of laccase activity.

Utility of total lower extremity radiography investigation of nonweight bearing in the young child.

OBJECTIVES: The purpose of this work was to determine the utility of total lower extremity radiographs versus dedicated tibia radiographs in the evaluation of the young child presenting with nonweight bearing without localizing signs. METHODS: This was an institutional review board-approved retrospective review of 263 consecutive patients between the ages of 9 months and 4 years who were referred for total lower extremity radiography between September 29, 2001, and November 7, 2006. Among these, a total of 133 study subjects met inclusion criteria of presentation with nonweight bearing without localizing signs or history of previous trauma. The control population was selected from 1089 consecutive patients between the ages of 9 months and 4 years evaluated from January 5, 1999 and December 8, 2006, who had only tibia radiographs at presentation. From this group, a final control population of 128 patients was selected with similar presentation of nonweight bearing without localizing signs or history of previous trauma. Causes of nonweight bearing were recorded for both groups based on radiograph findings and additional studies performed during workup. RESULTS: At initial presentation, fractures were present in 13 study patients (9.8%) and in 23 control patients (17.9%). Total fractures (when including follow-up) were present in 14 study patients (10.5%) and in 26 control patients (20.3%). Fractures were located in the tibia alone in 100% of patients in the study group. Extratibial fracture (metatarsal) was present in 1 patient in the control group (0.7%). Among the study group, additional diagnoses included rickets (n = 1), cerebellar ataxia (n = 1), and discitis with epidural abscess (n = 1). CONCLUSIONS: Our study findings indicate that the diagnostic value of total lower extremity radiography is similar to dedicated tibia radiography in the workup of the nonweight-bearing young child without trauma history or localizing signs. Radiation and cost savings can be realized by reserving additional radiographs for patients with high clinical suspicion and normal findings on dedicated tibia radiography.

A real-time PCR method for the quantification of the two isoforms of metallothionein in Lake Trout (Salvelinus namaycush).

Metallothioneins (MTs) are low-molecular-weight proteins whose physiologic roles are the regulation of essential metals Cu and Zn, sequestration of heavy metals, and free radical scavenging. Induced production of MTs in a wide variety of organisms exposed to heavy metals has made them popular exposure indicators. While it has been postulated that the three different isoforms of MT play different physiologic roles, methods to discern induction separately have not been available. The development of real-time polymerase chain reaction (real-time PCR) primers and TaqMan probes to measure the two MT isoforms found in salmonid fish are described. Assuming a high degree of homology between the isoforms and within different groups of salmonids, the sequences for MT-I and MT-II from rainbow trout were used to develop primers and probes for lake trout using the Primer3 program. Two sections of each isoform that varied by only a few nucleotides were targeted. SYBR Green validated the primer specificity, and melt curve analysis further ensured that only one product was amplified. Analysis of archived samples from fish captured in unmanipulated reference lakes or from lakes experimentally treated with cadmium or ethynylestradiol (EE2) afforded an examination of seasonal and contaminant influences on MT-I and MT-II mRNA expression.

Developmental effects of bioaccumulated selenium in eggs and larvae of two salmonid species.

Elevated concentrations of Se have been detected in cold, flowing water habitats near uranium and coal mines in Canada. Fish from these systems have concentrations of Se in their tissues that exceed toxic effect thresholds that have been established for warm-water fishes. However, the applicability of toxic effect thresholds and guidelines to cold water, lotic habitats is a matter of contention in the literature since most cases of Se toxicosis have been documented in standing, warm-water systems. To examine the possibility of impaired reproduction in wild rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinusfontinalis) near coal mining activity in the northeastern slopes region of Alberta, Canada, spawn from both species were collected from exposure and reference sites. Gametes were fertilized in the laboratory, reared to the swim-up stage, and examined for deformities. A significant relationship was observed for rainbow trout between the amount of Se in eggs and the incidence of developmental abnormalities, specifically craniofacial defects, skeletal deformities, and edema. These associations approximate exponential functions with probabilities that 15% of the population would be affected occurring between 8.8 and 10.5 microg Se per gram of wet egg weight, based on probit analysis. These relationships are similar to those described for centrarchids inhabiting a seleniferous warm-water lake. No such relationships were established for brook trout.

Metabolism of selenomethionine by rainbow trout (Oncorhynchus mykiss) embryos can generate oxidative stress.

Although selenium is required by vertebrates, toxicity can arise at concentrations only slightly greater than those they require. The toxicity of Se is thought to arise from its ability to substitute for sulfur during the assembly of proteins. However, recent studies also indicate that some forms of selenium are capable of generating oxidative stress in an in vitro test system that includes glutathione. L-Selenomethionine, the predominant form of selenium in the eggs of oviparous vertebrates, does not generate oxidative radicals in this system, but lesions consistent with oxidative stress have been identified in fish and birds with high concentrations of Se. Here we report on the ability of rainbow trout embryos to transform L-Selenomethionine to a form capable of producing a superoxide radical. Oxidative stress appears to be generated by methioninase enzyme activity in the embryos that liberates methylselenol from l-Selenomethionine. Methylselenol redox cycles in the presence of glutathione producing superoxide and likely accounts for oxidative lesions present in fish and birds environmentally exposed to excessive loads of selenomethionine.

Waterborne ethynylestradiol induces vitellogenin and alters metallothionein expression in lake trout (Salvelinus namaycush).

Estrogenic contaminants isolated from waters receiving sewage treatment plant effluents are known to induce the egg yolk precursor vitellogenin (VTG) in male fish. Levels of the metal binding protein metallothionein (MT) have also been shown to be affected by estrogens in fish. It has been postulated that MT declines in estrogen exposed fish to facilitate transfer of the essential metal Zn to cellular components required for VTG synthesis. To examine the changes in MT and VTG concentrations in fish exposed to an estrogen contaminant, lake trout (Salvelinus namaycush) were exposed to waterborne ethynylestradiol at 0, 4, 40 or 400 ng/l(-1) for 21 days. Blood and tissues were collected after 21 days of exposure to measure circulating levels of VTG as well as MT concentrations in liver and kidney. VTG increased in male and female fish from all three exposure groups compared to control fish. MT in liver significantly decreased in males and females compared to the controls, in the two highest exposures. MT in kidney was significantly higher in both sexes of fish exposed to the two highest concentrations of ethynylestradiol. These data are supportive of a relationship between estrogen exposure and the regulation of MT. Further studies to examine the specific links between estrogen exposure, VTG induction and regulation of essential metals like Zn are required.