Lazarus-type tumour response to therapy with nivolumab for sarcomatoid carcinomas of the lung.

Pulmonary sarcomatoid carcinoma (psc) is a rare subtype of non-small-cell lung carcinoma with a poor prognosis and poor response to chemotherapy and radiotherapy. A previous study reported that psc expresses high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumours. We report 2 cases of patients with a lung sarcomatoid carcinoma. Both patients initially underwent curative lung resection, but developed early recurrent disease. Because PD-L1 was highly expressed in the tumour cells, we initiated therapy with nivolumab, which showed good efficacy, almost complete radiologic tumour remission, and a remarkable improvement in the condition of those patients. Immune checkpoint inhibitors targeting PD-1 might be a valuable therapy option for pscs.

Microbial heat resistance of Listeria monocytogenes and the impact on ready-to-eat meat quality after post-package pasteurization.

Several methods using bactericides, hydrostatic pressure, and post-package pasteurization technologies to control Listeria monocytogenes (LM) in ready-to-eat meats have been attempted. In addition to controlling LM contamination, any newly developed technology must have minimal effects on organoleptic properties. The objectives of this study were to: (1) determine the heat resistance of LM in two brands (A and B) of bologna differing in formulations, and, (2) evaluate the effects of post-package pasteurization on product quality. Fat content did not affect LM heat resistance in bologna at 55, 60, and 65°C; however, Brand B bologna had a numerically lower inactivation rate. Microbial heat resistance differed (P<0.05) with changes in pasteurization temperature. Time and temperature affected (P<0.05) cook-loss and L(∗) Hunter color value for both bologna brands. These data show that post-package pasteurization is effective but suggest that meat formulations may need modification to prevent development of negative quality characteristics.

Contributions of bone density and geometry to the strength of the human second metatarsal.

We investigated, at the whole bone level, the contribution of bone density and geometry to the fracture load of the second metatarsal, a bone that is prone to stress fracture. Dual-energy X-ray absorptiometry (DXA) was used to determine the areal bone mineral density (BMD), projected area of bone, and bone mineral content. Peripheral quantitative computed tomography (pQCT) was used to determine the volumetric cortical bone mineral density (vCtBMD) and cross-sectional moment of interia. Various metatarsal linear dimensions were also measured. The load at failure in cantilever bending was determined. The only linear dimension that had a significant correlation with load at failure was the height of the metatarsal base (r(2) = 0.30, p = 0.008). Utilizing all of the information provided by DXA gave no greater indication of whole bone strength than just BMD alone (adjusted r(2) = 0.40, p = 0.001). Using all of the information provided by pQCT gave no greater indication of whole bone strength than just vCtBMD alone (r(2) = 0. 46, p < 0.001). Volumetric cortical density and BMD were strongly correlated (r(2) = 0.81, p < 0.001). Our data suggest that, in the human second metatarsal, a variable such as material strength (as inferred from cortical density), and not geometry, may be the major factor in determining cantilever load to failure.

Accuracy and precision of radiostereometric analysis in the measurement of THR femoral component translations: human and canine in vitro models.

Radiostereometric analysis (RSA) is used to measure translations of joint replacement components with respect to the host bone in vivo. We used two cadaveric models of hip arthroplasty, one human and one canine, to evaluate the accuracy and precision of RSA-based estimates of translations of the femoral component with respect to the femur under ideal conditions. The femoral components were attached rigidly to a micrometer stage that provided standard displacements in increments of 25 and 50 microm in the interval from zero to 500 microm along three orthogonal axes. Radiostereometric examinations were performed for each increment. Accuracy was calculated as the 95% prediction intervals from regression analyses between the measured and actual displacements. Precision was evaluated as the standard deviation of five repeated measurements of a 200 microm displacement along each axis. Both accuracy and precision were best along the longitudinal axis, with a prediction interval of +/-47 microm in the human model and +/-45 microm in the canine model and a standard deviation of 30 microm in the human model and 40 microm in the canine model. The use of only the prosthetic head as a landmark (as opposed to three markers placed on the femoral stem) led to a 3-fold larger prediction interval in the human model and a 2-fold greater prediction interval in the canine model.

Stem curvature and load angle influence the initial relative bone-implant motion of cementless femoral stems.

A 6 df measurement system was used to investigate the initial relative bone-implant motion of two types of cementless total hip replacement femoral components-a straight stem and a curved stem. Five pairs of fresh frozen femurs from human cadavers were tested with loads applied to the femoral head at angles characteristic of level walking, stair-climbing, and rising from a chair. The most important findings were that (a) the resultant proximal translations were twice as high with the straight stem as with the curved stem at load angles encountered in stair-climbing and rising from a chair, (b) both stem types had more motion at load angles encountered in stair-climbing and rising from a chair than in level walking, with the increases ranging from 3 to 14-fold, (c) there was as much as 66-fold more motion distally than proximally, and (d) the amount of interface motion varied by 5-fold between the medial and lateral surfaces of the distal part of the implant because of the combined effects of translation and rotation. The amount of initial bone-implant motion of the femoral component was found to be particularly sensitive to off-axis loading; this suggests that stair-climbing and rising from a chair should be avoided in the early postoperative period when a cementless porous-coated femoral stem has been used.

Distribution of Young's modulus in the cancellous bone of the proximal canine tibia.

Canine cancellous bone is used as a model for human bone in experimental orthopedic research, including models of total knee arthroplasty. Depth-force measurements produced by small-diameter indentation testing were used to derive the variation of Young's modulus over the transverse cross-sectional surface at three levels within the proximal canine tibia. At the most proximal section the presence of lateral and medial peaks of equal modulus (approximately 1100 MPa) was found. Modulus averages for the three resection levels revealed a trend of distally decreasing values, from 692 MPa proximally to 417 MPa distally. Average regional modulus values for the canine tibia were 50-75% higher than previously reported for the tibia of healthy young adult humans, although the local maxima were only 5-20% greater in canines.

Initial in vitro stability of the tibial component in a canine model of cementless total knee replacement.

The tibial component of a canine cementless total knee replacement model was used to determine the degree to which pegs and screws contributed to the initial in vitro stability of the device. Three implant designs were investigated: (1) a four-peg implant in which cortical bone screws passed through the pegs, (2) the four-peg implant without adjuvant screw fixation, and (3) a flat implant with screws placed in the same positions as in the first design. For measuring the interface motion, the tibial component and proximal tibia were modeled as rigid bodies and an experimental method was developed which permitted all six degrees of freedom of the motion between these two objects to be determined. In tests performed to validate this methodological approach, the potential confounding influences of tibial deformation and differential amounts of tibial deformation with the use of screws or pegs were shown to be minimal, supporting the use of the rigid-body method. In general, the areas of greatest motion were at the periphery of the bone-implant interface, regardless of whether or not screws or pegs were used. The components secured with screws had up to five-fold reductions in interface motion compared to components which had pegs but lacked screw fixation. Components with pegs and screws and components with screws only had the same amount of interface motion. Thus, in the presence of screw fixation, the addition of pegs did not increase the stability of the tibial component.

pQCT provides better prediction of canine femur breaking load than does DXA.

Our study was designed to examine the validity of dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) measurements as predictors of whole bone breaking strength in beagle femora. DXA was used to determine the bone mineral content, bone area, and 'areal' bone mineral density. PQCT was used to determine the cross-sectional moments of inertia, volumetric densities of the bone, and to calculate bone strength indices based on bone geometry and density. A three-point bending mechanical test was used to determine maximal load. Three variables from the pQCT data set explained 88% of the variance in maximal load, with the volumetric bone mineral density explaining 32% of the variance. The addition of the volumetric cortical density increased the adjusted r(2) to 0.601 (p=0.001) and the addition of an index created by multiplying volumetric cortical bone density by the maximum cross-sectional moment of inertia made further significant (p<0.001) improvements to an adjusted r(2) of 0.877. In comparison, when only the DXA variables were considered in a multiple regression model, areal bone mineral density was the only variable entered and explained only 51% (p<0.001) of the variance in maximal load. These results suggest that pQCT can better predict maximal load in whole beagle femora since pQCT provides information on the bone's architecture in addition to its volumetric density.

Nondestructive measurements of implant-bone interface shear modulus and effects of implant geometry in pull-out tests.

Push-out and pull-out tests are used for destructive evaluation of implant-bone interface strength. Because nondestructive mechanical tests would allow maintenance of an intact interface for subsequent morphological study, we developed such a test to determine the shear modulus of the interface by measuring the shear deformation of a thin layer adjacent to the implant. A polyurethane foam model was used to test the experimental setup on a group of nine cylindrical implants with three different lengths (15-48 mm) and three different diameters (5-9.7 mm). The shear modulus of the interface, as calculated from the pull-out test, was validated against the shear modulus of the foam derived from tensile tests. The two values of shear modulus were well correlated (R2 = 0.8, p < 0.001), thus encouraging further application of the setup for tests of implant-bone interface mechanics. In addition, we also examined the effects of implant length and diameter. The length of the implants had a significant influence on the interface shear modulus (p < 0.05), indicating that comparisons of the variable should only be made of implants with the same length. The length and diameter of the implants were not critical parameters for the ultimate fixation strength.

Dimensional characteristics of uncomplicated autopsy-retrieved acetabular polyethylene liners by ultrasound.

A new, in vitro ultrasound-based method to measure the thickness of acetabular polyethylene components was developed and applied to 26 uncomplicated autopsy retrieved components and 40 unused components. The average age at total hip arthroplasty was 62 years and the average time in service of the retrieved components was 49 months. The clinical notes indicated that each of the arthroplasties was functioning well at the time of the patients death. Thickness distributions in the retrieved components had two distinct patterns. Eighteen of the retrieved components (69%) had their thinnest areas self-contained and located near the polar point. In the other 8 retrieved components (31%) the areas of minimum thickness were adjacent to the rim. Thickness distribution in the unused cups was predominately concentric with the thinnest area located near the polar point (85% of the cups). Detection limits for dimensional change were established based on the variability found in the unused liners. Fifteen of the 26 retrieved components (58%) had areas of reduced thickness which exceeded the detection limits; the average thickness reduction rate for these components was 0.076 mm per year. The other 11 retrieved components (42%) lacked such areas. The 15 cups with areas of reduced thickness had a longer time in service (63 +/- 18 months) than the 11 cups without areas of reduced thickness (32 +/- 25 months) (p = 0.003), but no other clinical factor (age, gender, Harris hip score, size and inclination of the cup, type of femoral fixation) was associated with these 15 cups. Cylindrical models to estimate volumetric change tended to underestimate the actual changes, suggesting that the actual particulate burden may be greater than previously appreciated. Finding that the pattern of thickness reduction can vary suggests that distinctive hip loading modes may be present postoperatively in patients with total hip arthroplasty. The wear rates of these components are consistent with wear rates calculated from radiographic data for well-functioning implants and are considerably lower than wear rates calculated for surgically-retrieved implants, indicating that autopsy-derived retrievals may be more representative of the majority of components currently in service than surgically-derived retrievals.

Implant stability in revision total hip arthroplasty: allograft bone packing following extended proximal femoral osteotomy.

One method of revising the femoral component in revision total hip arthroplasty in the presence of compromised femoral bone stock is to pack the upper femur with particulate allograft and then to cement the femoral component into the allograft bed. This technique is being used clinically with encouraging results. Additionally, surgical exposure of the femoral canal during revision total hip arthroplasty can be greatly improved with an extended trochanteric osteotomy, which is subsequently repaired with wires or cables. To assess the feasibility of performing the allograft bone packing technique following an extended trochanteric osteotomy, the stability of this construct in a cadaver model was measured, using micromotion sensing instruments and loads applied on a materials testing machine. The stability of the cemented allograft impaction construct following extended trochanteric osteotomy was comparable to the stability of the control construct, which consisted of a similar impacted allograft construct without osteotomy. The stability of the osteotomized side was comparable to that of the control side. It is concluded that the initial in vitro stability of the allograft impaction technique following extended proximal femoral osteotomy is adequate to justify experimental in vivo use.

Effects of fixation technique on displacement incompatibilities at the bone-implant interface in cementless total knee replacement in a canine model.

Bone-implant displacements can be caused by rigid body motion and by differences in material properties of the implant and bone. In the present study of the tibial component in total knee replacement, we tested a series of tibial component fixation designs to determine how certain design features influenced the magnitude of the tangential displacement between the component and supporting bone in a canine model. The transverse expansion of the proximal tibia under static axial loading was measured in the intact tibia and then in the same bone following implantation of tibial components with different interface characteristics: cementless flat smooth, cementless flat porous-coated, cementless flat porous-coated with screws, cementless pegged porous-coated, cementless pegged porous-coated with screws, cemented pegged, and cemented pegged with screws. In all cases, the magnitude of the transverse expansion increased with higher applied loads. When the statistical analysis was restricted to the cementless interfaces, the presence/absence of the porous coating, the presence/absence of pegs, and the use of screws had no significant influence on tibial expansion. However, in an analysis including the cemented and cementless pegged components, tibial expansion was reduced with the use of screws. The magnitude of the interface motion due to these displacement incompatibilities was approximately fivefold lower than the amount of interface motion related to rigid body motion found in a separate study with the canine model. The measured expansion was similar in the intact tibiae and the implanted tibiae, suggesting that the transverse constraint in the canine proximal tibia must be provided by the surrounding cortical ring rather than the subchondral bone.

Impacted particulate allograft for femoral revision total hip arthroplasty. In vitro mechanical stability and effects of cement pressurization.

The initial migration and micromotion of the revision femoral stem stabilized with morselized impacted cancellous allograft and bone-cement and the influence of cement pressurization on fixation of the cement/allograft composite to the host were examined with human cadaver femurs. The stability of the allograft/cemented reconstruction was found to be intermediate between those of conventional cemented and cementless stems. In most cases, the stability of the reconstruction was closer to that of cemented than to that of cementless stems. This may account for histologic findings of graft incorporation in experimental and retrieved specimens reported by other authors. Although increased cement pressurization led to greater penetration of cement into the graft bed, greater cement penetration did not increase fixation strength of the cement/allograft composite to the host.

Bone graft harvesting from the distal radius, olecranon, and iliac crest: a quantitative analysis.

The purpose of this study was to quantify the volume and density of cancellous bone available from 3 commonly used bone graft sites in upper extremity surgery: the distal radius, olecranon process, and anterior iliac crest. Sixteen cadavers (age range, 59-98 years) with no prior history of bone harvest or metabolic conditions affecting bone were used. Cancellous graft was obtained using standardized techniques designed to simulate the clinical setting. Packed cancellous bone volume was determined as the volume occupied by the harvested bone after compression packing with a uniform load. Defect volume was determined by measuring the volume of the site from which bone was harvested. The distal radius and olecranon provided similar volumes of packed cancellous bone (2.7 and 2.8 cc, respectively). The anterior iliac crest provided approximately twice this amount (5.3 cc). The packed cancellous bone volume/defect volume ratio was not different between the 3 sites studied. Male gender was associated with a significantly greater amount of packed cancellous bone volume for all sites. We believe the olecranon to be an alternative to the distal radius as a source of bone graft for upper extremity procedures. We suggest using the anterior iliac crest when a large volume of cancellous bone is required.

Combined submerged and solid substrate fermentation for the bioconversion of lignocellulose.

A novel two-stage bioreactor has been designed for a combined submerged (SF) and solid substrate fermentation (SSF) of wheat straw. The straw was pretreated with steam, and cellulases from the culture fluid of Trichoderma reesei were adsorbed on it for increased bioconvertibility. SSF was conducted in the top part of the bioreactor by inoculating the straw with a 36-h mycelial culture of T. reesei, or Coriolus versicolor. In the bottom part of the fermenter, Endomycopsis fibuliger was grown in SF. The SF liquor was recirculated through the SSF stage at 24 h intervals to remove glucose and other metabolites that may inhibit growth, and to maintain optimum moisture level and temperature. The removed glucose and other metabolites provided nutrients for the yeast in the SF stage. The combined fermentation resulted in overall higher biomass yield, increased bioconversion, increased cellulase production, and increased digestibility compared with single SSF or SF.

Relationship between articular cartilage damage and bone density in the first metatarsal.

It is well known that bone changes occur in relationship to the articular cartilage damage seen in osteoarthritis. Numerous studies have shown a relationship between bone density and articular cartilage damage in knee and hip joints, but it is controversial as to whether or not an increased subchondral bone density results in greater cartilage damage. We studied 49 pairs of cadaveric first metatarsals in an attempt to correlate the level of cartilage damage seen on the distal articular surface with areal and volumetric density and other parameters such as bone geometry. A positive correlation was detected between articular cartilage damage and bone density by peripheral quantitative computed tomography in five of eight frontal slices in the head of the left metatarsal in the male sample only. The more extensive subchondral cysts found in the right male metatarsal may have contributed to the lack of correlation between the two variables on the right side. In addition, females displayed significantly greater osteophytosis than males at a given grade of cartilage damage, thus, possibly leading to a painful, apropulsive gait and a disuse osteopenia which would neutralize any subchondral bone density increase associated with cartilage damage. Microscopic investigations are, therefore, warranted to detect bone changes on a more discreet level, particularly within the subchondral plate.

Bone density of the human talus does not increase with the cartilage degeneration score.

Osteoarthritis (OA) is a common, disabling condition of synovial joints that can eventually lead to reduced, or lost, mobility. It is characterized by both articular cartilage degeneration and subchondral bone changes. However, a cause-and-effect relationship between the two tissues remains controversial. Increased subchondral bone density has been associated with early degenerative changes in the cartilage of knee, hip, and finger joints-joints in which progressive changes to OA are common. In contrast, the ankle joint is known to exhibit early cartilage changes, but is not prone to the development of OA. In the present study, it was found that cartilage degeneration on the talus is not associated with an increase in bone density, as assessed through peripheral quantitative computed tomography (pQCT).