For more than a century researchers have studied Maya ruins, and sites like Tikal, Palenque, Copán, and Chichén Itzá have shaped our understanding of the Maya. Yet the lowlands of Belize, which were ...once home to a rich urban tradition that persisted and evolved for almost 2,000 years, are treated as peripheral to these great Classic period sites. The hot and humid climate and dense forests are inhospitable and make preservation of the ruins difficult, but this oft-ignored area reveals much about Maya urbanism and culture.
Using data collected from different sites throughout the Maya lowlands, including the Vaca Plateau and the Belize River Valley, Brett Houk presents the first synthesis of these unique monuments and discusses methods for mapping and excavating. Considering the sites through the theoretical lenses of the built environment and ancient urban planning, Houk vividly reconstructs their political history, how they fit into the larger political landscape of the Classic Maya, and how the ancient cities fell apart over time.
Maya kings who failed to ensure the prosperity of their kingdoms were subject to various forms of termination, including the ritual defacing and destruction of monuments and even violent death. This ...is the first comprehensive volume to focus on the varied responses to the failure of Classic period dynasties in the southern lowlands. The contributors offer new insights into the Maya "collapse," evaluating the trope of the scapegoat king and the demise of the traditional institution of kingship in the early ninth century AD--a time of intense environmental, economic, social, political, and even ideological change.
Bone mineral density (BMD) estimates for the proximal femur using Dual Energy X-ray Absorptiometry (DXA) are currently considered the standard for making a diagnosis of osteoporosis in an individual ...patient using BMD alone. We have compared BMD results from a commercial Quantitative CT (QCT) BMD analysis system, "CTXA Hip", which provides clinical data for the proximal femur, to results from DXA. We have also used CTXA Hip to determine cortical and trabecular contributions to total BMD. Sixty-nine patients were scanned using 3D QCT and DXA. CTXA Hip BMD measurements for Total Hip and Femoral Neck were compared to DXA results. Twenty-two women were scanned at 0, 1, 2 years and CTXA Hip and DXA results analyzed for long-term reproducibility. Long-term reproducibility calculated as root-mean-square averages of SDs in vivo was 0.012 g/cm2 (CV = 1.8%) for CTXA Total Hip and 0.011 g/cm2 (CV = 2.0%) for CTXA Femoral Neck compared to 0.014 g/cm2 (CV = 2.0%) and 0.016 g/cm2 (CV = 2.7%), respectively, for DXA. The correlation of Total Hip BMD CTXA vs. DXA was R = 0.97 and for Femoral Neck was R = 0.95 (SEE 0.044 g/cm2 in both cases). Cortical bone comprised 62±5% (mean ± SD) of total hipbone mass in osteoporotic women. CTXA Hip provides substantially the same clinical information as conventional DXA and in addition provides estimates of BMD in separate cortical and trabecular bone compartments, which may be useful in evaluation of bone strength.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
TPX-100, a promotor of osteoblast and chondroblast differentiation, is a potential osteoarthritis (OA) therapy. This retrospective study compared MRI 3D femoral bone shape changes ...(
B
-scores) after intra-articular TPX-100 or placebo and analyzed the relationship between cartilage thickness and bone shape change over 12 months.
Methods
One hundred and four participants with bilateral moderate to severe knee cartilage defects were randomized to receive TPX-100 (200 mg) or placebo. Each subject’s contralateral placebo-treated knee served as a paired internal control. After MRI quality control, 78/93 subjects (84%; 156 knees) were analyzed for quantitative femoral
B
-score and cartilage thickness. All analyses were performed centrally, blind to treatment assignment and clinical data.
Results
TPX-100-treated knees (
n
= 78) demonstrated a statistically significant decrease in pathologic bone shape change compared with placebo-treated knees at 6 and 12 months: 0.0298 (95% C.I. − 0.037, 0.097) vs 0.1246 (95% C.I. 0.067, 0.182) (
P
= 0.02), and 0.0856 (95% C.I. 0.013, 0.158) vs. 0.1969 (95% C.I. 0.123, 0.271) (
P
= 0.01), respectively. The correlation between bone shape change and medial and total tibiofemoral cartilage thickness changes at 12 months was statistically significant in TPX-100-treated knees (
P
< 0.01).
Conclusions
This is the first report of a potential therapy demonstrating a significant effect on bone shape measured by
B
-score in knee OA. These data, in combination with previously reported statistically significant and clinically meaningful improvements in WOMAC physical function versus placebo, support TPX-100 as a candidate for disease modification in knee OA.
Trial registration
NIH ClinicalTrials.gov,
NCT01925261
. Registered 15 August 2013
Osteophytes are commonly used to diagnose and guide knee osteoarthritis (OA) treatment, but their causes are unclear. Although they are not typically the focus of knee arthroplasty surgeons, they can ...predict case difficulty and length. Furthermore, their extent and location may yield much information about the knee joint status. The aims of this computed tomography–based study in patients awaiting total or partial knee arthroplasty were to: (1) measure osteophyte volume in anatomical subregions and relative change as total volume increases; (2) determine whether medial and/or lateral OA affects osteophyte distribution; and (3) explore relationships between osteophytes and OA severity.
Data were obtained from 4,928 computed tomography scans. Machine-learning-based imaging analyses enabled osteophyte segmentation and quantification, divided into anatomical regions. Mean three-dimensional joint space narrowing was assessed in medial and lateral compartments. A Bayesian model assessed the uniformity of osteophyte distribution. We correlated femoral osteophyte volumes with B-scores, a validated OA status measure.
Total tibial (25%) and femoral osteophyte volumes (75%) within each knee correlated strongly (R2 = 0.85). Medial osteophytes (65.3%) were larger than lateral osteophytes (34.6%), with similar proportions in both the femur and tibia. Osteophyte growth was found in all compartments, and as total osteophyte volume increased, the relative distribution of osteophytes between compartments did not markedly change. No evidence of variation was found in the regional distribution of osteophyte volume between knees with medial, lateral, both, or no three-dimensional joint space narrowing in the femur or tibia. There was a direct relationship between osteophyte volume and OA severity.
Osteophyte volume increased in both medial and lateral compartments proportionally with total osteophyte volume, regardless of OA location. The peripheral position of femoral osteophytes does not appear to contribute to load-bearing. This suggests that osteophytic growth represents a ‘whole-knee’/global response. This work may have broad applications for knee OA, both surgically and nonoperatively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Central dual-energy X-ray absorptiometry (DXA) of the lumbar spine and proximal femur is the preferred method for bone mineral density (BMD) testing. Despite the fracture risk statistics, ...osteoporosis testing with DXA remains underused. However, BMD can also be assessed with quantitative computed tomography (QCT) that may be available when access to DXA is restricted. For patients undergoing a primary CT study of the abdomen or pelvis, a potential opportunity exists for concurrent BMD screening by QCT without the need for any additional imaging, radiation exposure, or patient time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
For patients undergoing contrast-enhanced CT examinations that include the proximal femur, an opportunity exists for concurrent screening bone mineral density (BMD) measurement. We investigated the ...effect of IV contrast enhancement on CT-derived x-ray absorptiometry areal BMD measurement.
Our cohort included 410 adults (mean age, 65.3 ± 10.0 years; range, 49-95 years) who underwent split-bolus CT urography at 120 kVp. Areal femoral neck BMD in g/cm(2) was measured on both unenhanced and contrast-enhanced CT series with asynchronous phantom calibration. Constant offset and multiplicative factor corrections for the contrast-enhanced series were derived from the Bland-Altman plot linear regression slopes.
Mean unenhanced and contrast-enhanced areal femoral neck BMD values were 0.681 ± 0.118 and 0.713 ± 0.123 g/cm(2), respectively. The SD of the distribution of residuals for the constant offset and multiplicative model corrections were 0.0232 and 0.0231, respectively. The constant offset correction associated with contrast enhancement was 0.032 ± 0.023 g/cm(2), which corresponds to 0.29 ± 0.21 T-score units using the CT-derived x-ray absorptiometry young normal areal femoral neck BMD reference SD of 0.111 g/cm(2).
For the purposes of opportunistic osteoporosis screening, contrast-enhanced abdominopelvic CT studies are equivalent to unenhanced CT and can therefore be used for femoral neck BMD assessment. This measure could greatly enhance osteoporosis screening.
▪
Introduction: Approximately 30-35% of patients with classic Hodgkin Lymphoma will prove refractory to frontline therapy or relapse subsequently. Traditional second-line chemotherapy regimens ...including ifosfamide, carboplatin, and etoposide (ICE) result in complete response rates of ~50%. Achievement of complete metabolic response (CMR) assessed by PET/CT imaging prior to autologous hematopoietic stem cell transplant (AHSCT) predicts favorable progression free survival (PFS) and overall survival (OS). PD-1 blockade is a well-established therapeutic strategy for the treatment of cHL. Pembrolizumab (PEM) is a checkpoint inhibitor targeting PD-1 currently FDA approved as monotherapy in relapsed cHL. We hypothesized that PEM in combination with ICE (PEM-ICE) chemotherapy would be a safe and effective regimen that would yield high CMR rates prior to AHSCT.
Methods: This single arm, phase II, multi-institutional clinical trial evaluated the addition of PEM to ICE chemotherapy in AHSCT eligible patients with relapsed and refractory cHL (NCT03077828). The regimen consisted of 21 day cycles of PEM 200 mg IV on day 1 with standard ICE including ifosfamide 5 g/m2 with MESNA as a 24hr continuous infusion on day 2, carboplatin AUC 5 IV (max 800 mg) on day 2, and etoposide 100 mg/m2/day IV on days 1 to 3. Two cycles of PEM-ICE were followed by stem cell mobilization/collection. One cycle of PEM 200 mg IV monotherapy was then administered. Our primary endpoint was the rate of CMR on PET/CT (PET2) imaging defined as a Deauville score of ≤ 3. Images were reviewed centrally. An optional third cycle of PEM-ICE was permitted for patients achieving CMR to allow for appropriate timing of AHSCT. Secondary objectives included clinical outcomes (PFS and OS), safety and tolerability, and transplantation related metrics including ability to collect stem cells and time to engraftment.
Results: A total of 42 patients were enrolled with 37 patients evaluable for the primary endpoint. Median age was 34 (19-70) with female predominance (n=27, 64%). 16 patients had primary refractory disease. The CMR rate assessed by PET/CT imaging following 2 cycles of PEM-ICE was 86.5% (95% CI, 71.2-95%), meeting our primary endpoint of improvement over historical outcomes to 70%. The PET2 ORR was 97.3% with 11% PR and 2.7% PD. PET2 scores were Deauville 1 in 45% (n=17), Deauville 2 in 27.0% (n=10), Deauville 3 in 8.1% (n=3), Deauville 4 in 13.5% (n=5), and Deauville 5 in 5.4% (n=2). New areas of PET-positivity in two cases were biopsied showing noncaseating granuloma in one case and EBV but no cHL in another. Five patients received the optional third cycle of PEM-ICE chemotherapy with 35 of the 37 evaluable patients proceeding to AHSCT. Seven patients had radiation as part of the conditioning regimen with an additional 4 patients receiving consolidative radiation following transplant. After a median follow up of 27 months, the median PFS was 26.9 months with survival probability at 24 months of 88.2% (Figure 1). Median OS was not reached with too few events but remained 95.1% at 27 months. The addition of PEM to ICE did not impair stem cell mobilization and all patients successfully collected, with 35 (87%) within 2 apheresis sessions (range 1-7). No patients had engraftment delays or failure. Of the 42 patients, all received at least one dose of PEM and were therefore eligible for toxicity analyses. 34 patients (81%) experienced adverse events (AEs) attributed to PEM and 22 patients (52.3%) had grade 3-4 AEs comprised of cytopenias, elevated AST/ALT, hyponatremia, hypophosphatemia, and fatigue. Five patients had severe AEs attributed to PEM which included anemia, back pain, decreased EF, fever, and thrombocytopenia. There were no significant PEM-related autoimmune events that delayed a patient's treatment on protocol. There were two grade 5 toxicities on the protocol including a patient with cardiac arrest during stem cell collection and a patient with acute respiratory distress syndrome attributed to engraftment syndrome. Both were judged “possibly” related to PEM.
Conclusions: Pembrolizumab with ICE chemotherapy is a tolerable and efficacious regimen with high CMR rate as assessed by PET/CT. Despite short follow up, patients had excellent PFS and OS in the post-transplant setting. The results support further investigation of PEM-ICE as second-line treatment for AHSCT eligible patients with relapsed and refractory classical Hodgkin lymphoma.
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Casulo: BMS: Research Funding; Verastem: Research Funding; Genentech: Research Funding; Gilead: Research Funding. Allen: Kyowa Kirin: Consultancy, Honoraria, Research Funding; Daichii Sankyo: Consultancy, Honoraria; Secure Bio: Consultancy, Honoraria. Karmali: Epizyme: Consultancy; AstraZeneca: Speakers Bureau; Roche: Consultancy; Genentech: Consultancy; EUSA: Consultancy; Janssen/Pharmacyclics: Consultancy; Karyopharm: Consultancy; Morphosys: Consultancy, Speakers Bureau; BeiGene: Consultancy, Speakers Bureau; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Consultancy, Research Funding; Takeda: Research Funding. Gordon: Zylem Biosciences: Patents & Royalties: Patents, No royalties; Bristol Myers Squibb: Honoraria, Research Funding. Winter: Actinium Pharma: Consultancy; BMS: Other: Husband: Data and Safety Monitoring Board; Karyopharm (Curio Science): Honoraria; Novartis: Other: Husband: Consultancy, Data and Safety Monitoring Board; Merck: Consultancy, Honoraria, Research Funding; Ariad/Takeda: Other: Husband: Data and Safety Monitoring Board; Epizyme: Other: Husband: Data and Safety Monitoring Board; Agios: Other: Husband: Consultancy; Gilead: Other: Husband: Consultancy; Janssen: Other: Husband: Consultancy.
new combination of study agent with standard of care chemotherapy regimen
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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