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1.
Improvement in Tricuspid Annular Plane Systolic Excursion with Pulmonary Hypertension Therapy in Pediatric Patients 下载免费PDF全文
2.
Danielle E Whittier Elizabeth J Samelson Marian T Hannan Lauren A Burt David A Hanley Emmanuel Biver Pawel Szulc Elisabeth Sornay-Rendu Blandine Merle Roland Chapurlat Eric Lespessailles Andy Kin On Wong David Goltzman Sundeep Khosla Serge Ferrari Mary L Bouxsein Douglas P Kiel Steven K Boyd 《Journal of bone and mineral research》2022,37(3):428-439
Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
3.
L Joseph Melton S Vincent Rajkumar Sundeep Khosla Sara J Achenbach Ann L Oberg Robert A Kyle 《Journal of bone and mineral research》2004,19(1):25-30
To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable. 相似文献
4.
Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women. 总被引:1,自引:0,他引:1
Natthinee Charatcharoenwitthaya Sundeep Khosla Elizabeth J Atkinson Louise K McCready B Lawrence Riggs 《Journal of bone and mineral research》2007,22(5):724-729
After acute estrogen withdrawal in postmenopausal women, administration of anakinra or etanercept, specific blockers of IL-1 and TNF-alpha, respectively, reduced the rise in bone resorption markers to about one half of that in controls. This is consistent with an important role for these immune cytokines in mediating the effect of estrogen deficiency on bone. INTRODUCTION: Studies in rodents have implicated increased production of interleukin (IL)-1 beta and TNF-alpha as mediators of bone loss after ovariectomy, but their roles are unclear in humans whose immune system differs markedly from that of rodents. MATERIALS AND METHODS: We administered transdermal estradiol, 0.1 mg/d, for 60 days to 42 early postmenopausal women. Estrogen treatment was discontinued, and subjects were randomly assigned to intervention groups receiving 3 wk of injections with 0.9% saline, anakinra 100 mg/d, or etanercept 25 mg/twice weekly. Bone turnover was assessed by measuring serum carboxyl-terminal telopeptide of type 1 collagen (CTX) and amino-terminal telopeptide of type 1 collagen (NTX), markers for bone resorption, and serum amino-terminal propeptide of type 1 collagen (P1NP), a marker for bone formation. Results were expressed as percent change in markers from baseline (last 2 days of estrogen treatment and days 20 and 21 of intervention). RESULTS: The percent changes from baseline during intervention for serum CTX, urine NTX, and serum PINP, respectively, were 43.3 +/- 8.0%, 12.0 +/- 7.1%, and -41.0 +/- 2.5% for the control group; 25.9 +/- 6.3%, 9.5 +/- 4.0%, and -37.8 +/- 3.0% for the anakinra group; and 21.7 +/- 5.0%, 0.32 +/- 3.82%, and -34.5 +/- 3.9% for the etanercept group. Compared with the control group, the blunting of the increase in serum CTX fell just below the level of significance (p=0.10) after anakinra treatment, whereas the blunting of the increase in serum CTX (p=0.034) and in urine NTX (p=0.048) were significant after etanercept treatment. Other changes were not significant. CONCLUSIONS: The data are consistent with a role for TNF-alpha, and possibly for IL-1 beta, in mediating increased bone resorption during estrogen deficiency in women. Although either cytokine blocker reduced serum CTX by about one half, the effect of combined blockade could not be tested because of concerns about toxicity. The data do not exclude direct or indirect contributory roles for RANKL or for other cytokines. 相似文献
5.
Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. 总被引:8,自引:0,他引:8
Sundeep Khosla B Lawrence Riggs Elizabeth J Atkinson Ann L Oberg Lisa J McDaniel Margaret Holets James M Peterson L Joseph Melton 《Journal of bone and mineral research》2006,21(1):124-131
In a population-based cross-sectional study, we examined effects of sex and age on bone microstructure at the wrist using high-resolution 3-D pQCT. Compared with women, men had thicker trabeculae in young adulthood and had less microstructural damage with aging. These findings may contribute to the virtual immunity of men to age-related increases in wrist fractures. INTRODUCTION: Although changes in bone microstructure contribute to fracture risk independently of BMD, it has not heretofore been possible to assess this noninvasively in population-based studies. MATERIALS AND METHODS: We used high-resolution 3-D pQCT imaging (voxel size, 89 mum) to define, in a random sample of women (n = 324) and men (n = 278) 21-97 years of age, sex and age effects on bone microstructure at the wrist. RESULTS: Relative to young women (age, 20-29 years), young men had greater trabecular bone volume/tissue volume (BV/TV; by 26%, p = 0.001) and trabecular thickness (TbTh; by 28%, p < 0.001) but similar values for trabecular number (TbN) and trabecular separation (TbSp). Between ages 20 and 90 years, cross-sectional decreases in BV/TV were similar in women (-27%) and in men (-26%), but whereas women had significant decreases in TbN (-13%) and increases in TbSp (+24%), these parameters had little net change over life in men (+7% and -2% for TbN and TbSp, respectively; p < 0.001 versus women). However, TbTh decreased to a greater extent in men (-24%) than in women (-18%; p = 0.010 versus men). CONCLUSIONS: Whereas decreases with age in trabecular BV/TV are similar in men and women, the structural basis for the decrease in trabecular volume is quite different between the sexes. Thus, over life, women undergo loss of trabeculae with an increase in TbSp, whereas men begin young adult life with thicker trabeculae and primarily sustain trabecular thinning with no net change in TbN or TbSp. Because decreases in TbN have been shown to have a much greater impact on bone strength compared with decreases in TbTh, these findings may help explain the lower life-long risk of fractures in men, and specifically, their virtual immunity to age-related increases in distal forearm fractures. 相似文献
6.
Case report Leptomeningeal involvement in diffuse intrinsic brain stem gliomas is rarely diagnosed clinically and in majority of the instances diagnosed only on postmortem examination. We report two cases of diffuse pontine glioma diagnosed clinicoradiologically and treated with conventional radiotherapy.Observations On follow-up, both patients showed clinical features suggestive of meningeal spread although imaging for pontine tumor showed stable disease. Leptomeningeal disease in the spine was confirmed on imaging and in one case by cerebrospinal fluid examination also. During the follow-up of patients with pontine glioma, the possibility of leptomeningeal involvement must be borne in mind. 相似文献
7.
Shreyasee Amin B Lawrence Riggs Elizabeth J Atkinson Ann L Oberg L Joseph Melton Sundeep Khosla 《Journal of bone and mineral research》2004,19(7):1075-1083
The role of the IGFs and IGFBPs on age-related changes in BMD in adult men and women is not well understood. Studying an age-stratified community based sample of 344 men and 276 women, we found higher IGFBP-2 levels to be associated with lower BMD. IGFBP-2, which increases with age in both men and women, was the strongest, most consistent predictor of BMD among the IGF/IGFBPs studied. INTRODUCTION: Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of tissue growth and metabolism, but their association with BMD in adult men and women is controversial. MATERIALS AND METHODS: In an age-stratified, random sample of the community population, we examined the role of serum levels of IGF-I, IGF-II, and IGFBP-1, -2, and -3 on BMD of the proximal femur (total hip), lateral spine, midshaft, and ultradistal radius as measured by DXA. We explored the association before and after adjustment for potential confounders, including age, bioavailable estradiol and testosterone, sex hormone binding globulin (SHBG), and measures of total fat and skeletal muscle mass. RESULTS: We studied 344 men (age, 23-90 years) and 276 women (age, 21-93 years; 166 postmenopausal) not on hormone replacement or oral contraceptives. In both men and women, IGF-I and IGFBP-3 levels fell with advancing age, whereas IGFBP-2 levels tended to rise with age. There was an inverse association of IGFBP-2 with BMD at most skeletal sites in men and both premenopausal and postmenopausal women, whereas lower IGF-I and IGFBP-3 were associated with lower BMD in men and postmenopausal women only. Lower IGF-II was associated with lower BMD in men only. There were no associations between IGFBP-1 and BMD in either sex. After adjustment for age, in most cases, we found no further associations between IGF-I, IGF-II, or IGFBP-3 and BMD. In contrast, after age adjustment, higher IGFBP-2 remained a predictor of lower BMD in men and postmenopausal women at all sites except for the lateral spine (for men: r = -0.21, -0.20, and -0.19, all p < 0.001; and for postmenopausal women: r = -0.34, -0.24, and -0.25, all p < 0.01, for the total hip, midshaft, and ultradistal radius, respectively). IGFBP-2 remained an independent negative predictor of BMD in men, postmenopausal women, and all women combined after additional adjustment for bioavailable sex steroids, but not at all sites after adjustment for SHBG and muscle mass. In premenopausal women, IGFBP-2 had similar associations as seen in postmenopausal women, but they were weaker and not statistically robust. CONCLUSIONS: Among the IGF/IGFBPs in our study, IGFBP-2 was a key negative predictor of BMD among men and women, particularly postmenopausal women. Our findings suggest a potential role of the IGF/IGFBP system in regulating bone loss in aging men and women and identify a previously under-recognized, potentially deleterious role for IGFBP-2, a known inhibitor of IGF action that increases with age in both sexes. Whether the action of the IGF/IGFBP system on bone metabolism is mediated partly through its effects on muscle mass or SHBG deserves further study. 相似文献
8.
Practicing Behavioral Sex Therapy in India: Selection, Modifications, Outcome, and Dropout 总被引:1,自引:0,他引:1
A file review of 178 male patients with sexual dysfunction revealed that high income, married status, presence of partner at evaluation, and liberal attitude towards sexuality increased the chances of selection for behavioral sex therapy. The outcome of therapy was associated with treatment adherence. Participation of the conjoint unit resulted in lower dropout rates. 相似文献
9.
BACKGROUND: A common problem facing patients suffering from psoriasis is the need for surgery that requires incision through active psoriatic skin. Many patients have been denied surgery because of the fear of an increased risk of infection, decreased wound healing ability, and worsening of the psoriatic lesions. OBJECTIVE: To assess the practices and beliefs of dermatologists and surgeons (orthopedic and plastic surgeons) faced with the decision of whether to operate through active psoriatic skin. METHODS: Dermatologists, orthopedic surgeons, and plastic surgeons selected from various professional membership lists from five representative cities were sent a survey to ascertain their opinions on operating on active psoriatic skin. Psoriatic patients were also given forms asking about the severity of their psoriasis and whether they had ever been denied surgery. RESULTS: Dermatologists are more likely to condone surgery in active psoriatic skin and to believe that there is not a risk of increased infection or decreased wound healing than are orthopedic surgeons and plastic surgeons. These findings are statistically significant (P<0.05). CONCLUSION: With proper preoperative measures and dermatologic treatment, surgery can be performed on active psoriatic skin in most cases with minimal reservations, although a controlled, prospective study is necessary to arrive at a definitive conclusion. 相似文献
10.
Cauda equina nerve sheath tumors are usually small, well-encapsulated tumors. Sometimes they may attain very large proportions, cause extensive bony changes, and resemble ependymomas in the cauda equina. They may also infiltrate into adjacent soft tissue planes and retroperitoneal spaces and yet be histologically benign. An awareness of this entity ensures aggressive surgical removal at the time of exploration. Primary neuro-fibrosarcomas or malignant changes in primary nerve sheath tumors of the cauda equina are seen in patients with neurofibromatosis. 相似文献