3D Printable Modular Soft Elastomers from Physically Cross-linked Homogeneous Associative Polymers.

Three-dimensional (3D) printing of elastomers enables the fabrication of many technologically important structures and devices. However, there remains a critical need for the development of reprocessable, solvent-free, soft elastomers that can be printed without the need for post-treatment. Herein, we report modular soft elastomers suitable for direct ink writing (DIW) printing by physically cross-linking associative polymers with a high fraction of reversible bonds. We designed and synthesized linear-associative-linear (LAL) triblock copolymers; the middle block is an associative polymer carrying amide groups that form double hydrogen bonding, and the end blocks aggregate to hard glassy domains that effectively act as physical cross-links. The amide groups do not aggregate to nanoscale clusters and only slow down polymer dynamics without changing the shape of the linear viscoelastic spectra; this enables molecular control over energy dissipation by varying the fraction of the associative groups. Increasing the volume fraction of the end linear blocks increases the network stiffness by more than 100 times without significantly compromising the extensibility. We created elastomers with Young's moduli ranging from 8 kPa to 8 MPa while maintaining the tensile breaking strain around 150%. Using a high-temperature DIW printing platform, we transformed our elastomers to complex, highly deformable 3D structures without involving any solvent or post-print processing. Our elastomers represent the softest melt reprocessable materials for DIW printing. The developed LAL polymers synergize emerging homogeneous associative polymers with a high fraction of reversible bonds and classical block copolymer self-assembly to form a dual-cross-linked network, providing a versatile platform for the modular design and development of soft melt reprocessable elastomeric materials for practical applications.

Additive Manufacturing of Poly(phenylene Sulfide) Aerogels via Simultaneous Material Extrusion and Thermally Induced Phase Separation.

Additive manufacturing (AM) of aerogels increases the achievable geometric complexity, and affords fabrication of hierarchically porous structures. In this work, a custom heated material extrusion (MEX) device prints aerogels of poly(phenylene sulfide) (PPS), an engineering thermoplastic, via in situ thermally induced phase separation (TIPS). First, pre-prepared solid gel inks are dissolved at high temperatures in the heated extruder barrel to form a homogeneous polymer solution. Solutions are then extruded onto a room-temperature substrate, where printed roads maintain their bead shape and rapidly solidify via TIPS, thus enabling layer-wise MEX AM. Printed gels are converted to aerogels via postprocessing solvent exchange and freeze-drying. This work explores the effect of ink composition on printed aerogel morphology and thermomechanical properties. Scanning electron microscopy micrographs reveal complex hierarchical microstructures that are compositionally dependent. Printed aerogels demonstrate tailorable porosities (50.0-74.8%) and densities (0.345-0.684 g cm-3 ), which align well with cast aerogel analogs. Differential scanning calorimetry thermograms indicate printed aerogels are highly crystalline (≈43%), suggesting that printing does not inhibit the solidification process occurring during TIPS (polymer crystallization). Uniaxial compression testing reveals that compositionally dependent microstructure governs aerogel mechanical behavior, with compressive moduli ranging from 33.0 to 106.5 MPa.

Patterns of Failure in High-Grade Soft Tissue Sarcomas of the Extremities and Trunk Wall After Pre- or Postoperative Radiation Therapy.

Purpose: Radiotherapy (RT) is a mainstay of treatment for high-grade soft tissue sarcomas (STS). We sought to examine the pattern of local recurrence (LR) with regard to target volume, clinical course, and tumor characteristics in extremity and trunk wall STS patients receiving pre- or postoperative RT. Methods and Materials: In this retrospective study, LR rates and patterns in 91 adult patients with a primary diagnosis of localized high-grade STS of the extremities and trunk wall treated with pre- or postoperative RT at our institution between 2004 and 2021 were analyzed. Radiation treatment plans and imaging data sets at diagnosis and LR were compared. Results: Seventeen out of 91 (18.7 %) patients developed a LR after a median time of 12.7 months. In 10 out of 13 LRs (76.9%) with available treatment plans and radiographic imaging data at the time of recurrence, the LR occurred within the planned target volume (PTV), 2 LRs were marginal (15.4%, at the edge of the PTV volume), and one relapsed out-of-field (7.7%, outside the PTV volume). Positive surgical margins (microscopic or macroscopic) were found in 5 out of 91 patients (5.5%), 1 of which was found in the 17 patients with LRs (5.9%). Eleven of 13 LR patients (84.6%) with available treatment plans and radiographic imaging data received postoperative RT; the median total RT dose was 60 Gy. Volumetric-modulated arc therapy was used in 10 (76.9%), intensity-modulated RT in 2 (15.4%), and 3-dimensional conformal radiation therapy in 1 (7.7%) of 13 LRs. Conclusions: The majority of LRs occurred within the PTV suggesting that LR is most likely not a consequence of inadequate target volume definition, but rather of radioresistant tumor biology. To further improve local tumor control, future research on the potential of dose escalation with normal tissue sparing, STS subtype-specific tumor biology, radiosensitivity, and surgical technique is indicated.

Sarcoma Patients Admitted to the Intensive Care Unit (ICU): Predictive Relevance of Common Sepsis and Performance Parameters.

Purpose: Prognosis of sarcoma patients is improving, with a better understanding of sarcomagenesis revealing novel therapeutic targets. However, aggressive chemotherapy remains an essential part of treatment, bearing the risk of severe side effects that require intensive medical treatment. Available data on the characteristics and clinical outcome of sarcoma patients admitted to intensive care units (ICU) are sparse. Patients and Methods: We performed a retrospective analysis of sarcoma patients admitted to the ICU from 2005 to 2022. Patients ≥18 years with histologically proven sarcoma were included in our study. Results: Sixty-six patients were eligible for analysis. The following characteristics had significant impact on overall survival: sex (p=0.046), tumour localization (p=0.02), therapeutic intention (p=0.02), line of chemotherapy (p<0.001), SAPS II score (p=0.03) and SOFA score (p=0.02). Conclusion: Our study confirms the predictive relevance of established sepsis and performance scores in sarcoma patients. For overall survival, common clinical characteristics are also of significant value. Further investigation is needed to optimize ICU treatment of sarcoma patients.

Prosthetic Joint Infection in Mega-Arthroplasty Following Shoulder, Hip and Knee Malignancy-A Prospective Follow-Up Study.

INTRODUCTION: The risk of prosthetic joint infection (PJI) in mega-prosthesis for malignancy is increased compared with non-tumor cases. While several studies describe PJI in tumor-related arthroplasty, prospective studies comparing infection characteristics among different joints are limited. The present study analyzes mega-arthroplasty for hip, knee, and shoulder malignancy and compares the epidemiology, diagnosis, microbe spectrum, treatments, and outcomes between the different entities. METHODS: The retrospective inclusion criteria were as follows: (1) mega-arthroplasty (2) in the hip, knee, or shoulder joint and a total femur arthroplasty (3) following a malignant bone tumor or metastasis (4) between 1996 and 2019. All included patients were prospectively followed and invited for a renewed hospital examination, and their PJI characteristics (if identified) were analyzed using both retrospective as well as newly gained prospective data. A PJI was defined according to the Infectious Disease Society of America (IDSA) and re-infection was defined according to the modified Delphi Consensus criteria. RESULTS: In total, 83 cases of tumor mega-arthroplasty at a mean follow-up of 3.9 years could be included (32 knee, 30 hip, and 19 shoulder cases and 2 cases of total femur arthroplasty). In total, 14 PJIs were identified, with chondrosarcoma in 6 and osteosarcoma in 3 being the leading tumor entities. Knee arthroplasty demonstrated a significantly higher rate of PJI (p = 0.027) compared with hips (28.1% vs. 6.7%), while no significant difference could be found between the knee and shoulder (10.5%) (p = 0.134) or among shoulder and hip cases (p = 0.631). The average time of PJI following primary implantation was 141.4 months in knee patients, 64.6 in hip patients, and 8.2 months in shoulder patients. Age at the time of the primary PJI, as well as the time of the first PJI, did not show significant differences among the groups. Thirteen of the fourteen patients with PJI had a primary bone tumor. Statistical analysis showed a significant difference in the disadvantage of primary bone tumors (p = 0.11). While the overall cancer-related mortality in the knee PJI group (10%) was low, it was 50% in the hip and 100% in the shoulder group. CONCLUSION: The risk of PJI in knee tumor arthroplasty is significantly increased compared with hips, while cancer-related mortality is significantly higher in hip PJI cases. At the same time, mega-prostheses appear to be associated with a higher risk of infection due to a primary bone tumor compared with metastases. The study confirms existing knowledge concerning PJI in tumor arthroplasty, while, being one of the few studies to compare three different joints concerning PJI characteristics.

Surgical Margins in Soft Tissue Sarcoma Management and Corresponding Local and Systemic Recurrence Rates: A Retrospective Study Covering 11 Years and 169 Patients in a Single Institution.

Soft tissue sarcomas (STSs) are a diverse group of rare malignant soft tissue tumors with a high disease burden. Treatment protocols are complex and, to this day, a precise recommendation for the surgical margin width is lacking. The present study aims to analyze the width of the surgical margins in STS resection specimens and analyze them for local and systemic disease-free survival as well as for most frequent histologic STS subtypes. A total of 169 consecutive patients diagnosed and treated in curative intent in our institution following a primary and localized STS of the extremities or trunk from January 2010 to December 2020 were included in this study regardless of age. Our data reveal that low-grade STSs are best controlled locally by a surgical margin ≥2 mm and in this way also preventing distant metastases effectively. Local recurrence-free survival and metastasis-free survival in high-grade STS were improved by intact muscle fascia or periosteum at the margin when compared only to soft tissue. However, the outcome was independent of the surgical margin width, suggesting a close but negative margin may be safe in high-grade STS subtypes with less invasive growth patterns when combined with adjunct radiochemotherapy.

Preoperative hypofractionated radiotherapy for soft tissue sarcomas: a systematic review.

BACKGROUND: Soft tissue sarcomas (STS) represent a diverse group of rare malignant tumors. Currently, five to six weeks of preoperative radiotherapy (RT) combined with surgery constitute the mainstay of therapy for localized high-grade sarcomas (G2-G3). Growing evidence suggests that shortening preoperative RT courses by hypofractionation neither increases toxicity rates nor impairs oncological outcomes. Instead, shortening RT courses may improve therapy adherence, raise cost-effectiveness, and provide more treatment opportunities for a wider range of patients. Presumed higher rates of adverse effects and worse outcomes are concerns about hypofractionated RT (HFRT) for STS. This systematic review summarizes the current evidence on preoperative HFRT for the treatment of STS and discusses toxicity and oncological outcomes compared to normofractionated RT. METHODS: We conducted a systematic review of clinical trials describing outcomes for preoperative HFRT in the management of STS using PubMed, the Cochrane library, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Embase, and Ovid Medline. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Trials on retroperitoneal sarcomas, postoperative RT, and hyperthermia were excluded. Articles published until November 30th, 2021, were included. RESULTS: Initial search yielded 94 articles. After removal of duplicate and ineligible articles, 13 articles qualified for analysis. Eight phase II trials and five retrospective analyses were reviewed. Most trials applied 5 × 5 Gy preoperatively in patients with high-grade STS. HFRT courses did not show increased rates of adverse events compared to historical trials of normofractionated RT. Toxicity rates were mostly comparable or lower than in trials of normofractionated RT. Moreover, HFRT achieved comparable local control rates with shorter duration of therapy. Currently, more than 15 prospective studies on HFRT + / - chemotherapy are ongoing. CONCLUSIONS: Retrospective data and phase II trials suggest preoperative HFRT to be a reasonable treatment modality for STS. Oncological outcomes and toxicity profiles were favorable. To date, our knowledge is mostly derived from phase II data. No randomized phase III trial comparing normofractionated and HFRT in STS has been published yet. Multiple ongoing phase II trials applying HFRT to investigate acute and late toxicity will hopefully bring forth valuable findings.

The role of neoadjuvant radiochemotherapy in the management of localized high-grade soft tissue sarcoma.

BACKGROUND: Standard treatment of soft tissue sarcoma (STS) of the extremities includes limb-sparing surgery combined with pre- or postoperative radiotherapy (RT). The role of perioperative chemotherapy (CTX) remains uncertain. STS patients with high-risk features for local recurrence, distant metastases, and increased mortality may require additional systemic therapy. The objective of this study was to evaluate predictors of outcome regarding local control (LC), overall survival (OS), and freedom from distant metastases (FFDM) in a large single-center cohort of patients suffering from localized high-grade STS (grade 2/3, G2/G3). Special emphasis was put on a subgroup of patients who received combined neoadjuvant radiochemotherapy (RCT). METHODS: Overall, 115 adult STS patients were included in this retrospective study. The median follow-up was 34 months. Twenty-three patients (20.0%) were treated with neoadjuvant RCT, 92 (80.0%) received other therapies (adjuvant RT alone (n = 58); neoadjuvant CTX + adjuvant RT (n = 17); adjuvant RCT (n = 10), neoadjuvant RT alone (n = 7)). To assess potential prognostic factors on LC, OS, and FFDM, univariate (UVA) and multivariable (MVA) Cox proportional hazards models were applied. RESULTS: UVA showed significantly better LC rates in the neoadjuvant RCT group (p = 0.025), with trends in MVA (p = 0.057). The 3-year LC rate was 89.7% in the neoadjuvant RCT group vs. 75.6% in the "other therapies" group. UVA also showed significantly better OS rates in the neoadjuvant RCT group (p = 0.049), however, this was not confirmed in MVA (p = 0.205), the 3-year OS rate was 85.8% for patients treated with neoadjuvant RCT compared to 73.5% in the "other therapies" group. UVA showed significantly better FFDM rates in (p = 0.018) and a trend towards better FFDM rates in MVA (p = 0.059). The 3-year FFDM rate was 89.7% for patients treated with neoadjuvant RCT compared to 65.9% in the "other therapies" group. In the subgroup of patients with G3 STS, neoadjuvant RCT was a significant positive predictor of LC and FFDM in MVA (p = 0.047, p = 0.027) but not for OS. Overall grade 3 and 4 toxicities were significantly higher (p = 0.019) in the neoadjuvant RCT group and occurred in 73.9% vs. 38.0% in patients receiving other therapies. CONCLUSIONS: The results suggest that neoadjuvant RCT might improve LC and FFDM in patients with localized G3 STS while also being associated with increased acute complication rates. Further prospective research is warranted to confirm these findings.

Comorbidities rather than older age define outcome in adult patients with tumors of the Ewing sarcoma family.

BACKGROUND: Ewing family of tumors (EFT) is rarely diagnosed in patients (pts) over the age of 18 years (years), and data on the clinical course and the outcome of adult EFT pts is sparse. METHODS: In this retrospective analysis, we summarize our experience with adult EFT pts. From 2002 to 2020, we identified 71 pts of whom 58 were evaluable for the final analysis. RESULTS: Median age was 31 years (18-90 years). Pts presented with skeletal (n = 26), and extra-skeletal primary disease (n =32). Tumor size was ≥8 cm in 20 pts and 19 pts were metastasized at first diagnosis. Between the age groups (≤25 vs. 26-40 vs. ≥41 years) we observed differences of Charlson comorbidity index (CCI), tumor origin, as well as type and number of therapy cycles. Overall, median overall survival (OS) was 79 months (95% confidence interval, CI; 28.5-131.4 months), and median progression-free survival (PFS) 34 months (95% CI; 21.4-45.8 months). We observed a poorer outcome (OS, PFS) in older pts. This could be in part due to differences in treatment intensity and the CCI (<3 vs. ≥3; hazard ratio, HR 0.334, 95% CI 0.15-0.72, p = 0.006). In addition, tumor stage had a significant impact on PFS (localized vs. metastasized stage: HR 0.403, 95% CI 0.18-0.87, p = 0.021). CONCLUSIONS: Our data confirms the feasibility of intensive treatment regimens in adult EFT pts. While in our cohort outcome was influenced by age, due to differences in treatment intensity, CCI, and tumor stage, larger studies are warranted to further explore optimized treatment protocols in adult EFT pts.

A New System for Periprosthetic Fracture Stabilization-A Biomechanical Comparison.

In recent years, an increase in periprosthetic femur fractures has become apparent due to the increased number of hip replacements. In the case of Vancouver type B1 fractures, locking plate systems offer safe procedures. This study compared the distal lateral femur plate (LOQTEQ®, aap Implantate AG) with a standard L.I.S.S. LCP® (DePuy Synthes) regarding their biomechanical properties in fixation of periprosthetic femur fractures after hip arthroplasty. We hypothesized that the new LOQTEQ system has superior stability and durability in comparison. Eighteen artificial left femurs were randomized in two groups (Group A: LOQTEQ®; Group B: L.I.S.S. LCP®) and tested until failure. Failure was defined as 10° varus deformity and catastrophic implant failure (loosening, breakage, progressive bending). Axial stiffness, loads of failure, cycles of failure, modes of failure were recorded. The axial stiffness in Group A with 73.4 N/mm (SD +/- 3.0) was significantly higher (p = 0.001) than in Group B (40.7 N/mm (SD +/- 2.8)). Group A resists more cycles than Group B until 10° varus deformity. Catastrophic failure mode was plate breakage in Group A and bending in Group B. In conclusion, LOQTEQ® provides higher primary stability and tends to have higher durability.

Dissociative Carbamate Exchange Anneals 3D Printed Acrylates.

Relative to other additive manufacturing modalities, vat photopolymerization (VP) offers designers superior surface finish, feature resolution, and throughput. However, poor interlayer network formation can limit a VP-printed part's tensile strength along the build axis. We demonstrate that the incorporation of carbamate bonds capable of undergoing dissociative exchange reactions provides improved interlayer network formation in VP-printed urethane acrylate polymers. In the presence of dibutyltin dilaurate catalyst, the exchange of these carbamate bonds enables rapid stress relaxation with an activation energy of 133 kJ/mol, consistent with a dissociative bond exchange process. Annealed XY tensile samples containing a catalyst demonstrate a 25% decrease in Young's modulus, attributed to statistical changes in network topology, while samples without a catalyst show no observable effect. Annealed ZX tensile samples printed with layers perpendicular to tensile load demonstrate an increase in elongation at break, indicative of self-healing. The strain at break for samples containing a catalyst increases from 33.9 to 56.0% after annealing but decreases from 48.1 to 32.1% after annealing in samples without a catalyst. This thermally activated bond exchange process improves the performance of VP-printed materials via self-healing across layers and provides a means to change Young's modulus after printing. Thus, the incorporation of carbamate bonds and appropriate catalysts in the VP-printing process provides a robust platform for enhancing material properties and performance.

3D Printing Carbonaceous Objects from Polyimide Pyrolysis.

Fully aromatic polyimides are amenable to efficient carbonization in thin two-dimensional (2D) films due to a complement of aromaticity and planarity of backbone repeating units. However, repeating unit rigidity traditionally imposes processing limitations, restricting many fully aromatic polyimides, e.g., pyromellitic dianhydride with 4,4'-oxidianiline (PMDA-ODA) polyimides, to a 2D form factor. Recently, research efforts in our laboratories enabled additive manufacturing of micron-scale resolution PMDA-ODA polyimide objects using vat photopolymerization (VP) and ultraviolet-assisted direct ink write (UV-DIW) following careful thermal postprocessing of the three-dimensional (3D) organogel precursors to 400 °C. Further thermal postprocessing of printed objects to 1000 °C induced pyrolysis of the PMDA-ODA objects to disordered carbon. The pyrolyzed objects retained excellent geometric resolution, and Raman spectroscopy displayed characteristic disordered (D) and graphitic (G) carbon bands. Scanning electron microscopy probed the cross-sectional homogeneity of the carbonized samples, revealing an absence of pore formation during carbonization. Likewise, impedance analysis of carbonized specimens indicated only a moderate decrease in conductivity compared to thin films that were pyrolyzed using an identical carbonization process. Facile pyrolysis of PMDA-ODA objects now enables the production of carbonaceous monoliths with complex and predictable three-dimensional geometries using commercially available starting materials.

Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience.

BACKGROUND: The antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). However, recently the phase III ANNOUNCE trial could not confirm the additional value of olaratumab in this context. METHODS: Here, in a retrospective analysis we share our single-centre experience with olaratumab/doxorubicin in STS by including n = 32 patients treated with olaratumab/doxorubicin between 2016 and 2019. RESULTS: Median progression-free survival (PFS) in the overall cohort was 3.1 months (range 0.6-16.2). A response [complete remission (CR), partial remission (PR) or stable disease (SD)] was seen in n = 11 (34%) cases, whereas n = 21 (66%) patients showed progressive disease (PD). In n = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out of n = 5 patients receiving additional regional hyperthermia, n = 3 achieved PR or SD. CONCLUSIONS: This single-centre experience does also not support the promising phase Ib/II results for olaratumab/doxorubicin in STS. However, our findings do not preclude that olaratumab combination therapy could be valuable in a neoadjuvant setting. This warrants further exploration also taking into account the heterogeneous nature of STS.

Ultraviolet-Assisted Direct Ink Write to Additively Manufacture All-Aromatic Polyimides.

All-aromatic polyimides have degradation temperatures above 500 °C, excellent mechanical strength, and chemical resistance, and are thus ideal polymers for high-temperature applications. However, their all-aromatic structure impedes additive manufacturing (AM) because of the lack of melt processability and insolubility in organic solvents. Recently, our group demonstrated the design of UV-curable polyamic acids (PAA), the precursor of polyimides, to enable their processing using vat photopolymerization AM. This work leverages our previous synthetic strategy and combines it with the high solution viscosity of nonisolated PAA to yield suitable UV-curable inks for UV-assisted direct ink write (UV-DIW). UV-DIW enabled the design of complex three-dimensional structures comprising of thin features, such as truss structures. Dynamic mechanical analysis of printed and imidized specimens confirmed the thermomechanical properties typical of all-aromatic polyimides, showing a storage modulus above 1 GPa up to 400 °C. Processing polyimide precursors via DIW presents opportunity for multimaterial printing of multifunctional components, such as three-dimensional integrated electronics.

Neoadjuvant chemotherapy plus radiation versus chemotherapy plus regional hyperthermia in high-grade soft tissue sarcomas: a retrospective comparison.

PURPOSE: Localized adult high-grade soft tissue sarcomas (STS) usually require multimodality treatment including surgery, radiotherapy, chemotherapy and hyperthermia. If maximal preoperative tumor-shrinkage is envisaged, neoadjuvant chemotherapy + radiation (CRT) is often applied, however at the expense of relatively high toxicities and increased postoperative complication rates. This study aims to compare preoperative CRT with neoadjuvant chemotherapy + regional hyperthermia (HCT) regarding histopathological response, toxicity and outcome. METHODS: In this retrospective analysis, 61 consecutive high-grade STS patients treated between 2009 and 2016 were included. All patients were treated within a prospective treatment protocol. 28 patients received neoadjuvant CRT 33 patients HCT. CRT consisted of four cycles doxorubicin/ifosfamide and two cycles ifosfamide concomitant to 50.4 Gray external beam radiotherapy. HCT consisted of 4-6 cycles doxorubicin/ifosfamide with deep regional hyperthermia administered bi-weekly during each cycle. Association of treatment modality with overall survival (OS), local control (LC) and freedom from distant metastases (FFDM) was evaluated by Kaplan-Meier and log-rank analyses. RESULTS: The overall patient characteristics were well balanced. Histopathological tumor response did not differ significantly between both groups (p = .67), neither did higher-grade toxicities during neoadjuvant treatment. Wound dehiscence (p = .018) and surgical hospital re-admissions (p < .001) were both significantly more frequent in the CRT group. Two-year OS, LC and FFDM rates of all patients were 93, 85 and 71% with no significant differences between CRT and HCT. CONCLUSION: Compared to CRT, HCT seems equally efficient and appears to bear less surgical complications. Interpretation should be cautious due to the low number of patients and the retrospective nature of this study.

The provocative radiographic traction test for diagnosing craniocervical dissociation: a cadaveric biomechanical study and reappraisal of the pathogenesis of instability.

BACKGROUND CONTEXT: Craniocervical dissociation is a rare but serious condition, and missed injuries have been associated with poor neurologic outcomes and deterioration. A fluoroscopic traction test is employed to interrogate the craniocervical ligaments when clinical and imaging findings are equivocal. However, no specific protocol or known parameters with respect to traction or force applied have been established. PURPOSE: This study sought to define the parameters of the radiographic traction test with sequential sectioning of the primary ligamentous restraints under controlled distraction of the craniocervical junction in a biomechanical model. STUDY DESIGN: This is a cadaveric biomechanical study. METHODS: A custom loading apparatus applied traction forces in six specimens (O-C3) and the following ligaments were sectioned: alar, tectorial membrane, and occiput-C1 capsules to simulate varying degrees of craniocervical dissociation. Traction was applied 0 to 20 lb with fluoroscopy. Digital image analysis quantified the relative displacements of C0-C1, average craniocervical excursion, and under what load could a 2-mm craniocervical displacement be reproducibly recorded. RESULTS: A weight-distance table was produced and showed a marked loss of stability with sectioning of the ligaments and across all specimens in a similar pattern. Minimal translation was noted with sectioning of two of three ligaments in any order (<1-2 mm). All specimens exhibited a firm restraint to dissociation until the last of the three stabilizers was sectioned. Thus an "all-or-none" restraint to instability is present. All specimens failed at a weight of 5-10 lb (>2 mm). CONCLUSIONS: The current knowledge base of craniocervical injuries is very limited. This study shows that the key restraints to craniocervical instability are the alar ligaments, tectorial membrane, and the atlantooccipital joint capsules. Dissociation requires the complete incompetence of all three. The craniocervical traction test reliably demonstrates instability and requires no more than 5-10 lb of traction to perform.

Paranematic-to-nematic ordering of a binary mixture of rodlike liquid crystals confined in cylindrical nanochannels.

We explore the optical birefringence of the nematic binary mixtures 6CB_{1-x}7CB_{x} (0 ≤ x ≤ 1) embedded into parallel-aligned nanochannels of mesoporous alumina and silica membranes for channel radii of 3.4 ≤ R ≤ 21.0 nm. The results are compared with the bulk behavior and analyzed with a Landau-de Gennes model. Depending on the channel radius the nematic ordering in the cylindrical nanochannels evolves either discontinuously (subcritical regime, nematic ordering field σ<1/2) or continuously (overcritical regime, σ>1/2), but in both cases with a characteristic paranematic precursor behavior. The strength of the ordering field, imposed by the channel walls, and the magnitude of quenched disorder varies linearly with the mole fraction x and scales inversely proportionally with R for channel radii larger than 4 nm. The critical pore radius, R_{c}, separating a continuous from a discontinuous paranematic-to-nematic evolution varies linearly with x and differs negligibly between the silica and alumina membranes. We find no hints of preferred adsorption of one species at the channels walls. By contrast, a linear variation of the nematic-to-paranematic transition point T_{PN} and of the nematic ordering field σ versus x suggests that the binary mixtures of cyanobiphenyls 6CB and 7CB keep their homogeneous bulk stoichiometry also in nanoconfinement, at least for channel diameters larger than ∼7 nm.

Thermotropic orientational order of discotic liquid crystals in nanochannels: an optical polarimetry study and a Landau-de Gennes analysis.

Optical polarimetry measurements of the orientational order of a discotic liquid crystal based on a pyrene derivative confined in parallelly aligned nanochannels of monolithic, mesoporous alumina, silica, and silicon as a function of temperature, channel radius (3-22 nm) and surface chemistry reveal a competition of radial and axial columnar orders. The evolution of the orientational order parameter of the confined systems is continuous, in contrast to the discontinuous transition in the bulk. For channel radii larger than 10 nm we suggest several, alternative defect structures, which are compatible both with the optical experiments on the collective molecular orientation presented here and with a translational, radial columnar order reported in previous diffraction studies. For smaller channel radii our observations can semi-quantitatively be described by a Landau-de Gennes model with a nematic shell of radially ordered columns (affected by elastic splay deformations) that coexists with an orientationally disordered, isotropic core. For these structures, the cylindrical phase boundaries are predicted to move from the channel walls to the channel centres upon cooling, and vice-versa upon heating, in accord with the pronounced cooling/heating hystereses observed and the scaling behavior of the transition temperatures with the channel diameter. The absence of experimental hints of a paranematic state is consistent with a biquadratic coupling of the splay deformations to the order parameter.

Using simple imaging markers to predict prognosis in patients with aortic valve stenosis and unacceptable high risk for operation.

Aortic valve stenosis (AS) in patients >75 years of age is a challenge for diagnosis and management of every day clinical routine. Therefore, this clinical follow-up study aims to investigate predictors of death in patients with advanced stages of AS. In a single-center study, all patients (n = 157) with primary conservatively treated severe AS (mean age 78 ± 6 years) were included. All patients had initially refused aortic valve replacement (AVR). During a median follow-up of 2.6 years (quartiles 1.7, 3.8), 62 patients with severe AS switched to AVR and 95 remained conservatively treated (no AVR). Routine clinical data were assessed together with conventional echocardiography including the measurement of longitudinal wall function and deformation (mitral ring displacement and longitudinal strain and strain rate imaging). The end points were all-cause and cardiac death. During follow-up, cardiac death occurred in 49% in no-AVR group. In a Cox regression analysis, New York Heart Association functional class, valvuloarterial impedance, stroke volume, longitudinal strain and strain rate, and mitral annular displacement identified an increased risk of all-cause death (hazard ratio [HR] for mitral annular displacement 15.9, 95% confidence interval [CI] 6.24 to 40.86, p <0.001, positive predictive value 91%). In contrast, ejection fraction or EuroSCORE was not predictive (ejection fraction: HR 1.3, 95% CI 0.82 to 2.33, p = 0.25; EuroSCORE: HR 1.1, 95% CI 0.64 to 2.02, p = 0.64). Furthermore, in multivariate regression analysis, only longitudinal mitral annular displacement and longitudinal strain rate was a significant predictor of all-cause and cardiac death risk. These data show that prognosis in elderly patients with AS is determined by symptoms, hemodynamics, and particularly by cardiac long-axis function. Thus, for risk stratification, a comprehensive assessment of cardiac function including the measurement of longitudinal mitral annular displacement should be considered.

Influence of nanoconfinement on the nematic behavior of liquid crystals.

We explore the nematic ordering of the rodlike liquid crystals 5CB and 6CB, embedded into parallel-aligned nanochannels in mesoporous silicon and silica membranes as a function of mean channel radius (4.7 ≤ R ≤ .3 nm), and, thus, geometrical confinement strength, by optical birefringence measurements in the infrared region. The orientational order inside the nanochannels results in an excess birefringence, which is proportional to the nematic order parameter. It evolves continuously on cooling with a precursor behavior, typical of a paranematic state at high temperatures. These observations are compared with the bulk behavior and analyzed within a phenomenological model. Such an approach indicates that the strength of the nematic ordering fields σ is beyond a critical threshold σ(c) = 1/2 that separates discontinuous from continuous paranematic-to-nematic behavior. In agreement with the predictions of the phenomenological approach, a linear dependency of σ on the inverse channel radius is found and we can infer therefrom the critical channel radii, R(c) separating continuous from discontinuous paranematic-to-isotropic behavior, for 5CB (12.1 nm) and 6CB (14.0 nm). Our analysis suggests that the tangential anchoring at the channel walls is of similar strength in mesoporous silicon and mesoporous silica membranes. A comparison with the bulk phase behavior reveals that the nematic order in nanoconfinement is significantly affected by channel wall roughness, leading to a reduction of the effective nematic ordering.