Analysis of the need for surgery for different anatomical locations of splenic injury and radiologic intervention.

The splenic surface can be anatomically divided into the visceral surface connected to major blood vessels and the diaphragmatic surface attached to the diaphragm. This study aimed to investigate differences in future treatment and outcomes according to the anatomical location of splenic injuries following abdominal trauma. Patients who were treated at a single trauma center between January 2011 and April 2018 were included. The presence of lacerations or hematoma on the visceral surface was evaluated via computed tomography. Differences in the location of splenic surgery between a group that underwent surgical or radiologic intervention and a group that received conservative care only were analyzed. Of 355 patients with splenic injury analyzed, the total mortality rate was 15.2%. A total of 167 patients underwent surgery and angiographic embolization, and 168 received conservative care only. Splenic injuries involved the visceral surface in 127 and 105 patients in the respective groups. Significant differences in the incidence of splenic injuries involving the visceral surface were found between the two groups in the univariate and logistic regression analyses. The likelihood of needing surgery and treatments such as embolization was higher for cases of splenic injury involving the visceral surface than for splenic injuries that did not involve the visceral surface. Through additional research, it may become possible to analyze the location of a splenic injury to determine an effective and safe method of treatment and accurately predict a prognosis. Clin. Anat. 33:516-521, 2020. © 2019 Wiley Periodicals, Inc.

Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the ßIII isotype of tubulin.

The subunit protein of microtubules is tubulin, which has been the target for some of the most successful and widely used anti-tumor drugs. Most of the drugs that target tubulin bind to the ß subunit. There are many isotypes of ß-tubulin and their distributions differ among different tissues. The ßIII isotype is over-expressed in many tumors, particularly those that are aggressive, metastatic, and drug resistant. We have previously reported the design and synthesis of a series of compounds to fit the colchicine site on ßIII but not on the other isotypes. In the current study, we tested the toxicity and the anti-tumor activity of one of these compounds, CH-35, on the human breast tumor MDA-MB-231 over-expressing ßIII in a xenogeneic mouse model. We found that CH-35 was as toxic as Taxol® in vivo. Although the ßIII-over-expressing cells developed into very fast-growing tumors, CH-35 was more effective against this tumor than was Taxol. Our results suggest that CH-35 is a promising candidate for future drug development.

A bitter pill to swallow: dysphagia in cervical spine injury.

BACKGROUND: Dysphagia is a common complication after cervical spine trauma with spinal cord injury. We sought to characterize the prevalence of dysphagia within a total cervical spinal injury (CSI) population, considering the implications of spinal cord injury status and age on dysphagia development. We hypothesized that while greater rates of dysphagia would be found in geriatric and spinal cord-injured subgroups, all patients presenting with CSI would be at heightened risk for swallowing dysfunction. METHODS: All trauma admissions to a level II trauma center from January 2010 to April 2014 with CSI were retrospectively reviewed. CSI was classified as any ligamentous or cervical spinous fracture with or without cord injury. Patients failing a formal swallow evaluation were considered dysphagic. The implications of dysphagia development on age and spinal cord injury status were assessed in univariate and multivariate analyses. RESULTS: A total of 481 patients met study inclusion criteria, of which 123 (26%) developed dysphagia. Within the dysphagic subpopulation, 90 patients (73%) were geriatric, and 23 (19%) sustained spinal cord injury. The dysphagic subpopulation was predominantly free from spinal cord injury (81%). Multivariate analyses found age (adjusted odds ratio: 1.06; 95% confidence interval 1.04-1.07; P < 0.001) and spinal cord injury (adjusted odds ratio: 2.69; 95% confidence interval 1.30-5.56; P = 0.008) to be significant predictors of dysphagia development. CONCLUSIONS: Despite spinal cord-injured patients being at increased risk for dysphagia, most of the dysphagic subpopulation was free from spinal cord injury. Geriatric and CSI patients with or without cord injury should be at heightened suspicion for dysphagia development.

Long-Range Communication Network in the Type 1B Bone Morphogenetic Protein Receptor.

Protein-protein interactions are recognized as a fundamental phenomenon that is intimately associated with biological functions and thus are ideal targets for developing modulators for regulating biological functions. A challenge is to identify a site that is situated away from but functionally connected to the protein-protein interface. We employed bone morphogenetic proteins (BMPs) and their receptors as a model system to develop a strategy for identifying such a network of communication. Accordingly, using computational analyses with the COREX/BEST algorithm, we uncovered an overall pattern connecting various regions of BMPR-1B ectodomain, including the four conserved residues in the protein-protein interface. In preparation for testing the long-range effects of mutations of distal residues for future studies, we examined the extent of measurable perturbation of the four conserved residues by determination of the conformation and relative affinities of these BMPR-1B mutants for ligands BMP-2, -6, and -7 and GDF-5. Results suggest no significant structural changes in the receptor but do suggest that the four residues play different roles in defining ligand affinity and both intra- and intermolecular interactions play a role in defining ligand affinity. Thus, these results established two primary but necessary goals: (1) the baseline knowledge of perturbation of conserved interfacial residues for future reference and (2) the ability of the computational approach to identify the distal residues connecting to the interfacial residues. The data presented here provide the foundation for future experiments to identify the effects of distal residues that affect the specificity and affinity of BMP recognition. Protein-protein interactions are integral reactions in essentially all biological activities such as gene regulation and age-related development. Often, diseases are consequences of the alteration of these intermacromolecular interactions, which are thus recognized as a legitimate target for developing modulators for regulating biological functions. One approach is to design ligands that bind to the protein-protein interface. Another is to identify an allosteric site, an advantage of which is bypassing the potential challenge in competing for high-affinity interfacial interactions or a specific interface in a superassembly of multiple macromolecules. However, a challenge of this approach is identifying a site that is situated away from but functionally connected to the protein-protein interface.

Effective transport for trauma patients under current circumstances in Korea: a single institution analysis of treatment outcomes for trauma patients transported via the domestic 119 service.

In Korea, which still lacks a well-established trauma care system, the inability to transport patients to adequate treatment sites in a timely manner is a cause of low trauma patient survival. As such, this study was conducted to serve as a basis for the establishment of a future trauma transport system. We performed a comparative analysis of the transport time, and treatment outcomes between trauma victims transported by ground ambulance (GAMB) and those transported via the helicopter emergency medical service (HEMS) through the National Emergency Management Agency's 119 reporting system, which is similar to the 911 system of the United States, from March 2011 to May 2014. The HEMS-transported patients received treatment instructions, by remote communication, from our trauma specialists from the time of accident reporting; in certain instances, members of the trauma medical staff provided treatment at the scene. A total of 1,626 patients were included in the study; the GAMB and HEMS groups had 1,547 and 79 patients, respectively. The median transport time was different between 2 groups (HEMS, 60 min vs. GAMB, 47 min, P<0.001) but for all patients was 49 min (less than the golden hour). Outcomes were significantly better in the HEMS compared to the GAMB, using the trauma and injury severity score (survival rate, 94.9% vs. 90.5%; Z score, 2.83 vs. -1.96; W score, 6.7 vs. -0.8). A unified 119 service transport system, which includes helicopter transport, and the adoption of a trauma care system that allows active initial involvement of trauma medical personnel, could improve the treatment outcome of trauma patients.

Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells.

Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects.

Rapamycin inhibits BMP-7-induced osteogenic and lipogenic marker expressions in fetal rat calvarial cells.

Bone morphogenetic proteins (BMPs) promote osteoblast differentiation and bone formation in vitro and in vivo. BMPs canonically signal through Smad transcription factors, but BMPs may activate signaling pathways traditionally stimulated by growth factor tyrosine kinase receptors. Of these, the mTOR pathway has received considerable attention because BMPs activate P70S6K, a downstream effector of mTOR, suggesting that BMP-induced osteogenesis is mediated by mTOR activation. However, contradictory effects of the mTOR inhibitor rapamycin (RAPA) on bone formation have been reported. Since bone formation is thought to be inversely related to lipid accumulation and mTOR is also important for lipid synthesis, we postulated that BMP-7 may stimulate lipogenic enzyme expression in a RAPA-sensitive mechanism. To test this hypothesis, we determined the effects of RAPA on BMP-7-stimulated expression of osteogenic and lipogenic markers in cultured fetal rat calvarial cells. Our study showed that BMP-7 promoted the expression of osteogenic and lipogenic markers. The effect of BMP-7 on osteogenic markers was greater in magnitude than on lipogenic markers and was temporally more sustained. RAPA inhibited basal and BMP-7-stimulated osteogenic and lipogenic marker expression and bone nodule mineralization. The acetyl CoA carboxylase inhibitor TOFA stimulated the expression of osteoblast differentiation markers, whereas palmitate suppressed their expression. We speculate that the BMP-7-stimulated adipogenesis is part of the normal anabolic response to BMPs, but that inappropriate activation of the lipid biosynthetic pathway by mTOR could have deleterious effects on bone formation and could explain paradoxical effects of RAPA to promote bone formation.

T-cell acute lymphoblastic leukaemia after liver transplantation: post-transplant lymphoproliferative disorder or coincidental de novo leukaemia?

Post-transplant lymphoproliferative disorders of T-cell origin are quite uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three liver transplants, initially for biliary atresia and subsequently for graft failure due to chronic rejection. He had received immunosuppression with cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL occurred 16 years after the first liver transplant. This case highlights the challenge for classifying rare neoplasms occurring in recipients of solid organ transplants that are currently not recognized to lie within the spectrum of post-transplant lymphoproliferative disorders. Given the long interval between the liver transplants and the development of T-ALL, a coincidental occurrence of the leukaemia cannot be ruled out. However, the potential roles of immunosuppressive therapy and other co-morbid conditions of the individual as possible risk factors for the pathogenesis of T-ALL are discussed.

Immunohistochemical characterization of squamous differentiation and morular metaplasia in uterine endometrioid adenocarcinoma.

Squamous differentiation (SD) and morular metaplasia (MM) are frequently present in uterine endometrioid adenocarcinoma (EAC) and can mimic areas of solid tumor. We used immunohistochemical stains to further characterize these lesions, and to determine which markers would help to distinguish these metaplasias from areas of solid growth in EAC. The pathology database was searched for diagnoses of EAC from 1997 to 2007, the hematoxylin and eosin-stained slides were reviewed, and 143 cases with SD, MM, or both (SD+MM) were identified. A panel of immunohistochemical stains was performed. In particular, we were interested in PAX2 and PAX8, recently studied markers of Müllerian tissue as potential markers for differentiation of metaplasias and tumor. In addition, estrogen receptor and progesterone receptor, and Her-2/neu, were examined to determine whether there was a differential expression between the metaplasias and solid tumor that may be diagnostically useful. In addition, to further characterize MM and SD, bcl-2 as a marker of cell regulation and inhibition of apoptosis, p16 as a surrogate marker for human papillomavirus, and p63 as a marker of mature SD were studied. Adjacent normal endometrium (NEM), when present, and 20 EAC cases (FIGO Grades 1-3) without SD or MM served as controls. PAX2 was positive in NEM (58/61, 95%) and was lost in SD (15/136, 11%), MM (1/25, 4%), and EAC (57/163, 35%), whereas PAX8 was positive in all NEM (61/61, 100%) and in the majority of SD (125/136, 92%), MM (19/25, 73%), and EAC (162/163, 99%). The estrogen receptor and the progesterone receptor were expressed by the majority of EAC (148/163, 91% and 144/163, 88%, respectively), whereas both were markedly diminished in SD (56/136, 41% and 58/136, 43%) and MM (4/25, 16% and 2/25, 8%). Approximately half of the MM was positive for bcl-2 (12/25, 48%), making it an unreliable marker. Her-2/neu was negative in all cases (0%). p16 was patchy in SD (111/136, 82%), MM (22/25, 88%), and EAC (154/163, 94%), whereas p63 was predominantly positive only in SD (96/136, 71%). Estrogen receptor and progesterone receptor, PAX2, and PAX8 were helpful in differentiating MM from SD, EAC, or NEM (P<0.05). In addition, p63 distinguished between SD and MM, supporting the theory that morules do not show characteristic mature SD.

Acute adverse events from over-the-counter Chinese herbal medicines: a population-based survey of Hong Kong Chinese.

BACKGROUND: Although over-the-counter traditional Chinese herbal medicine (COTC) is commonly used to treat everyday illness in many parts of the world, no population-based study has been done to examine the prevalence and factors associated with COTC-related adverse events. METHODS: A cross-sectional telephone survey was conducted among Hong Kong Chinese adults in 2011 (n = 1100) with informed verbal consent. Stepwise logistic regression of demographic, attitudinal and behavioral variables was used to determine factors associated with past-year adverse events. RESULTS: Of study respondents, 71.7% (789/1100) reported past-year COTC use and 2.3% (25/1100) reported at least one COTC-related adverse event in the past year. Of the 27 adverse events cases reported among COTC users, the most common were allergic reactions (n = 11) dizziness (n = 5), and gastro-intestinal problems (n = 4). Pills/capsules were the dosage form that caused the highest proportion of adverse events (n = 10), followed by plasters (n = 7), creams/ointments (n = 5), and ingestible powders (n = 2).Although COTC users reporting adverse events were more likely to report greater practices to avoid adverse events (OR = 6.47; 95% CI: 1.38-30.3); they were also more likely to possess lower education levels (OR = 9.64, 95% CI: 2.20-42.3) and to have received COTC information from non-reliable, mass-media information sources such as magazines (OR = 3.32; 95% CI: 1.01-8.50) or television (OR = 2.93; 95% CI: 1.03-10.7). Package labels were also felt to be unclear by 42.9% of COTC users. A large proportion of COTC users demonstrated low levels of COTC-related knowledge, while the main impediment to greater information-seeking was the belief that reliable COTC information is not obtainable from Western health professionals. CONCLUSIONS: Despite global movements toward more stringent complementary medicine regulation, the limited accessibility of reliable information and widespread misperceptions among consumers present major challenges for the safe use of complementary medicine.

A host-guest relationship in bone morphogenetic protein receptor-II defines specificity in ligand-receptor recognition.

One of the most intriguing questions confronting the bone morphogenetic protein family is the mechanism of ligand recognition, because there are more ligands than receptors. Crystal structures of two type II receptors, ActR-II and BMPR-II, are essentially identical, and a loop structure (A-loop) has been suggested to play a role in determining ligand specificity. A solution biophysical study showed mutations of several A-loop residues in these two receptors exert different ligand binding effects. Thus, the issues of mechanism of ligand recognition and specificity remain unresolved. We examined effects of mutations of residues Y40, G47, and S107 in BMPR-II. These residues are not identified as being in contact with the ligand in the BMP-7-BMPR-II complex but are found mutated in genetic diseases. They are likely to be useful in identifying their roles in differentiating the various BMP ligands. Spectroscopic probing revealed little mutation-induced structural change in BMPR-II. Ligand binding studies revealed that Y40 plays a significant role in differentiating three distinct ligands; G47 and S107 affect ligand binding to a lesser extent. The role of the A-loop in ActR-II or BMPR-II is dependent on the host sequence of the receptor extracellular domain (ECD) in which it is embedded, suggesting a host-guest relationship between the A-loop and the rest of the ECD. Computational analysis demonstrated a long-range connectivity between Y40, G47, and S107 and other locations in BMPR-II. An integration of these results on functional energetics and protein structures clearly demonstrates, for the first time, an intradomain communication network within BMPR-II.

In a mature trauma system, there is no difference in outcome (survival) between Level I and Level II trauma centers.

BACKGROUND: The state of Pennsylvania (PA) has one of the oldest, most well-established trauma systems in the country. The requirements for verification for Level I versus Level II trauma centers within PA differ minimally (only in the requirement for patient volume, residency, and research). We hypothesized that there would be no difference in outcome at Level I versus Level II trauma centers. METHODS: Odds of mortality for 16 Level I and 11 Level II hospitals in PA over a 5-year period (2004-2008) was computed using a random effects logistic regression model. Overall adjusted mortality rates at Level I versus Level II hospitals were compared using the nonparametric Wilcoxon's rank sum test. The crude mortality rates for 140,691 patients over the 5-year period were similar (5.07% Level II vs. 5.48% Level I), but statistically significant (odds ratio mortality at Level I = 1.084, p = 0.002 Fisher's exact test). RESULTS: Although Level I centers had on average crude mortality rates that were higher than those of Level II centers, median adjusted mortality rates were not different for the two types of centers (Wilcoxon's rank sum test). Performance of Level I versus Level II shows considerable variability among centers (basic random effects model, age, blunt/penetrating, and Injury Severity Score [ISS]). However, Level II centers seem no different from Level I. CONCLUSION: As trauma systems mature, the distinction between Level I and Level II trauma centers blurs. The hierarchal descriptors "Level I" or "Level II" in a mature trauma system is pejorative and implies in those hospitals labeled "Level II" as inferior, and as such should be replaced with nonhierarchal descriptors.

Effects of cartilage-derived morphogenetic protein-3 on the expression of chondrogenic and osteoblastic markers in the pluripotent mesenchymal C3H10T1/2 cell line.

CDMP-3/GDF-7/BMP-12 treatment of pluripotent mesenchymal C3H10T1/2 cells resulted in a dose- and time-dependent change in cell morphology and in the expression of alkaline phosphatase, mRNA expression of osteocalcin, and bone sialoprotein, as well as mineralized bone nodule formation. CDMP-3 also stimulated Alcian Blue staining indicative of extracellular matrix formation without affecting aggrecan expression. CDMP-3 downregulated mRNA expression of BMP-4 and BMP-8A. CDMP-3 stimulated mRNA expression of ALK-1, ALK-2(ActR-IA), ALK-3(BMPR-IA), and ALK-4 without affecting that of ALK-6(BMPR-IB), ALK-7, and BMPR-II. These findings suggest that, under the experimental conditions studied, CDMP-3 induces the pluripotent mesenchymal C3H10T1/2 cells to express both chondrocytic and osteoblastic markers. The results further reveal potential complex interplay between the different bone morphogenetic proteins and their receptors in these processes.

Protein kinase D mediates the synergistic effects of BMP-7 and IGF-I on osteoblastic cell differentiation.

We previously showed that exogenous insulin-like growth factor-I (IGF-I) and bone morphogenetic protein-7 (BMP-7) synergistically stimulated osteoblast differentiation in fetal rat calvaria (FRC) cells. We have now shown that BMP-7 alone and the BMP-7 and IGF-I combination synergistically stimulated protein kinase D (PKD) phosphorylation at Ser744/748 and Ser916. Transfection of FRC cells with a constitutively active PKD stimulated marker expression, while transfection with a catalytically inactive PKD did not. Moreover, Gö6976, which inhibits protein kinase C (PKC) α and β1, blocked PKD phosphorylation and the synergistic action of the BMP-7 and IGF-I combination on osteoblast differentiation, whereas Gö6983, which inhibits PKCα, β, γ, δ, and ζ, did not. Our results suggest that the FRC cell differentiation induced by BMP-7 and the BMP-7 and IGF-I combination requires stimulation of PKD activity. Our results are consistent with a novel mechanism in which combined BMP-7 and IGF-I signaling activates upstream novel PKC(s), which then phosphorylates and activates PKD, leading to enhanced osteoblast differentiation.

Mucosa-associated lymphoid tissue lymphoma: multimodality imaging and histopathologic correlation.

OBJECTIVE: We will illustrate the imaging features of gastrointestinal and nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma and their correlation with histopathologic findings. The radiologic features to distinguish gastrointestinal MALT lymphoma from other types of lymphomas will also be described. CONCLUSION: Differences in clinical behavior and management make it exceedingly important to differentiate MALT lymphoma from other types of lymphomas. Radiologic and histopathologic findings need to be taken into account before making a diagnosis and treatment plan.

Application of a trauma intensivist model to a Level II community hospital trauma program improves intensive care unit throughput.

BACKGROUND: Critical care-trained trauma surgeons are the ideal care provider for severely injured patients. This "captain of the ship" (COS) assumes complete responsibility of the patient, from initial resuscitation to eventual discharge. Unlike American College of Surgeons-verified Level I centers, many nonacademic, community hospital trauma centers use a more fragmented approach, with care in the intensive care unit (ICU) delegated to a committee of multiple specialists. We hypothesized that dedicated trauma intensivists as COS in a community hospital could improve ICU outcome. METHOD: Beginning from September 2005, dedicated full-time trauma intensivists, without any resident coverage, assumed primary responsibility of all trauma patients admitted to a Level II Pennsylvania state verified trauma center. The ICU care was uninterrupted 24 hours a day, 365 days a year. Subspecialty consultations, for recommendations in care only, were selectively obtained as clinically indicated. We compared the 3 years before the implementation of the COS model (PRE: 2003-2005) with the 3 years after the model (POST: 2006-2008). A p-value ≤ 0.05 was considered significant. RESULTS: There were equal numbers of patients admitted to the ICU setting in both the periods. In the PRE and POST periods, both age (46.9 years vs. 52.4 years; p < 0.001) and Injury Severity Score (16.1 vs. 16.7; p = 0.01) were of significance. We observed significant differences in ventilator days (mean, 8 days vs. 6 days; p = 0.002) and mean ICU days (4.9 days vs. 4.4 days; p < 0.001) across the study periods. Days to tracheostomy also achieved statistical significance (9.1 vs. 8.1; p = 0.03). The number of medical consults decreased by 19% in the POST group (p < 0.001). Hospital stay days were not statistically different (7.4 vs. 7.2; p = 0.18). After adjusting for higher age and Injury Severity Score in the POST period, we noted no difference in the expected mortality rate. CONCLUSION: A trauma intensivist-driven model can be successfully adopted in a nonacademic community trauma program, without the need for a residency program. A decentralized ICU care model produces inefficiencies, diminishes the role of the trauma service, and decreases the overall throughput of trauma patients.

Assessment of minimal residual disease using multiparametric flow cytometry in patients with AL amyloidosis.

Despite achieving a hematologic complete response after treatment, many patients with AL amyloidosis do not attain recovery of organ function and/or experience hematologic relapse. A persistent plasma cell clone producing amyloidogenic light chains at levels below the detection threshold of traditional serologic methods is hypothesized to impede organ response in some patients. Assessment of minimal residual disease (MRD) may therefore have clinical importance as a more stringent treatment response tool for patients in a hematologic complete response. We used 2-tube, 10-color combination multiparametric flow cytometry to assess for MRD at a minimum sensitivity of 1 in 105 nucleated cells. Of 65 patients in hematologic complete response, 36 (55%) were found to have a residual clonal plasma cell population in the bone marrow. Comparing the MRD-negative and MRD-positive groups, renal response was observed in 88% vs 64% (P = .06), cardiac response in 75% vs 59% (P = .45), and any organ response in 90% vs 75% (P = .20) of patients. Depth of organ response as measured by the percent decrease in 24-hour proteinuria and brain natriuretic peptide was 96% vs 91% (P = .16) and 55% vs 46% (P = .66), respectively. These data suggest a possible correlation between MRD negativity and higher probability of organ response after treatment in AL amyloidosis. Future prospective studies with a larger cohort are needed to determine the clinical relevance of these improvements. This trial was registered at www.clinicaltrials.gov as #NCT00898235.

Triple-negative breast cancers are increased in black women regardless of age or body mass index.

INTRODUCTION: We investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis. METHODS: We identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression. RESULTS: 415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08). CONCLUSIONS: Black women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis.

A comparative study on BMP-induced osteoclastogenesis and osteoblastogenesis in primary cultures of adult rat bone marrow cells.

Bone remodeling is a process consisting of bone formation and resorption. The present study compared the relative osteoclastic and osteoblastic potency of bone morphogenetic proteins (BMP)-2, -4, -5, -6, and -7 in primary murine bone marrow cultures. All five BMPs stimulated, to varying degree, formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in a time- and protein concentration-dependent manner. The TRAP staining intensity correlated positively with the number of nuclei per TRAP-positive cell and the mRNA levels of colony-stimulating factor (CSF-1), receptor activator of nuclear factor kappaB ligand (RANKL), TRAP, and cathepsin K. Under osteogenic conditions, all five BMPs stimulated AP activity and mineralized bone nodule formation in a protein concentration-dependent manner in the same primary murine bone marrow cell culture system. These findings should be useful in designing treatment strategies for bone regeneration.

Metastatic interdigitating dendritic cell sarcoma masquerading as a skin primary tumor: a case report and review of the literature.

We report an unusual case of a lymph node interdigitating dendritic cell sarcoma (IDCS), metastatic to skin, in a 73-year-old patient. The patient initially presented as having a primary skin tumor with lymph node metastasis. The metastatic IDCS was initially read as an atypical fibroxanthoma. However, the morphology seen on the lymph node excision, paired with immunohistochemistry and electron microscopy studies, was diagnostic for an IDCS. Additional immunohistochemistry was performed on the shave biopsy, confirming that the skin tumor was a metastasis. IDCS is a rare tumor that belongs to the histiocytic and dendritic cell group of tumors. Diagnosing this entity is difficult without the aid of ancillary testing such as immunohistochemistry and electron microscopy. In the workup of a spindle cell neoplasm, IDCS should be included in the differential diagnosis.