For older women, the majority of hip fragility fractures and radiographic vertebral fragility fractures occur among the densitometrically osteoporotic population: a literature analysis.

It has been frequently cited that 'the majority of fragility fractures (FF) occur at non-osteoporotic bone mineral density (BMD)'. For the reports with T-score measured around the time of a hip fracture, we conducted a systematic literature search in December 2022, and resulted in 10 studies with five for Caucasian women and five for East Asian women. Femoral neck (FN) T-score was reported in five Caucasian studies and three East Asian studies, three of five Caucasian studies had a mean T-score ≤-2.5, and one study had the majority of their patients measuring a mean T-score ≤-2.5. All three East Asian studies reported a mean FN T-score ≤-2.7. Total hip T-score was reported in two Caucasian studies and three East Asian studies, the two Caucasian studies both had a mean T-score ≤-2.5, and all three East Asian studies had a mean T-score ≤-2.6. A new literature search conducted in April 2024 results in additional three studies, with results being consistent with the data described above. A trend was noted that 'younger' patients suffer from hip fractures at a 'higher' T-score. For the highly cited articles where the notion the majority of FF occur at non-osteoporotic BMD was derived from, authors reported prospective epidemiological studies where BMD was not measured at the timepoint of hip fracture, instead, BMD was measured at the study baseline. These epidemiological studies suggest that >50% of hip fractures likely occur in women with an osteoporotic FN or hip T-score. However, a pattern was seen that older men suffer from hip fracture at a notably higher T-score than older women. For the cases of radiographic vertebral FF, despite varying criteria being used to classify these FFs, the majority of female patients had spine densitometric osteoporosis. Literature shows, compared with the cases of hip fracture, distal forearm fracture occurs at a 'younger' age and 'higher' BMD, suggesting distal forearm fracture is more likely associated with a 'higher' trauma energy level.

Higher perfusion of rectum carcinoma relative to tumor-free rectal wall: quantification by a new imaging biomarker diffusion-derived vessel density (DDVD).

Background: Diffusion-derived vessel density (DDVD) is a physiological surrogate of the area of micro-vessels per unit tissue area. DDVD is calculated according to: DDVD(b0b5) = Sb0/ROIarea0 - Sb5/ROIarea5, where Sb0 and Sb5 refer to the tissue signal when b is 0 or 5 s/mm2. This study applied DDVD to assess the perfusion of rectal carcinoma (RC). Methods: MRI was performed with a 3.0-T magnet. Diffusion weighted image with b-values of 0, 5 s/mm2 were acquired in 113 patients with non-mucinous RC and 15 patients with mucinous RC. Diffusion-derived vessel density ratio [DDVDr(b0b5)] was DDVD(b0b5) of RC divided by DDVD(b0b5) of tumor-free rectal wall. Results: The median value of the DDVDr(b0b5) for non-mucinous RCs was 1.430, with the majority of RCs showing a higher DDVD than the adjacent tumor-free wall [i.e., with DDVDr(b0b5) >1]. 90.3% (102/113) of non-mucinous RCs were hypervascular, 1.77% (2/113) were iso-vascular, and 7.96% (9/113) were hypovascular. The median value of the DDVDr(b0b5) for mucinous RCs was 1.660. 73.3% (11/15) of mucinous RCs were hypervascular, and 26.7% (4/15) were hypovascular. A trend (P=0.09) was noted that earlier clinical grades non-mucinous RCs had a higher DDVDr(b0b5) than those of the advanced clinical grades (2.245 for grade 0&I, 1.460 for grade II, 1.430 for grade III, 1.130 for grade IV). A non-significant trend was noted with well and moderately differentiated non-mucinous RCs had a higher DDVDr(b0b5)than that of poorly differentiated non-mucinous RCs (median: 1.460 vs. 1.320). A non-significant trend was noted with MRI-detected extramural vascular invasion (mrEMVI) positive non-mucinous RCs had a higher DDVDr(b0b5) than that of mrEMVI negative non-mucinous RCs (1.630 vs. 1.370). Conclusions: DDVD results in this study approximately agree with contrast agent dynamically enhanced CT literature data.

Radiological diagnosis of prevalent osteoporotic vertebral fracture on radiographs: an interim consensus from a group of experts of the ESSR osteoporosis and metabolism subcommittee.

When a low-energy trauma induces an acute vertebral fracture (VF) with clinical symptoms, a definitive diagnosis of osteoporotic vertebral fracture (OVF) can be made. Beyond that, a "gold" radiographic standard to distinguish osteoporotic from non-osteoporotic VFs does not exist. Fracture-shaped vertebral deformity (FSVD) is defined as a deformity radiographically indistinguishable from vertebral fracture according to the best of the reading radiologist's knowledge. FSVD is not uncommon among young populations with normal bone strength. FSVD among an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely to be associated with compromised bone strength. In more severe grade deformities or when a vertebra is collapsed, OVF diagnosis can be made with a relatively high degree of certainty by experienced readers. In "milder" cases, OVF is often diagnosed based on a high probability rather than an absolute diagnosis. After excluding known mimickers, singular vertebral wedging in older women is statistically most likely an OLVF. For older women, three non-adjacent minimal grade OLVF (< 20% height loss), one minimal grade OLVF and one mild OLVF (20-25% height loss), or one OLVF with ≥ 25% height loss, meet the diagnosis of osteoporosis. For older men, a single OLVF with < 40% height loss may be insufficient to suggest the subject is osteoporotic. Common OLVF differential diagnoses include X-ray projection artifacts and scoliosis, acquired and developmental short vertebrae, osteoarthritic wedging, oncological deformities, deformity due to high-energy trauma VF, lateral hyperosteogeny of a vertebral body, Cupid's bow, and expansive endplate, among others.

Diffusion-derived vessel density (DDVD) computed from a simple diffusion MRI protocol as a biomarker of placental blood circulation in patients with placenta accreta spectrum disorders: A proof-of-concept study.

OBJECTIVES: Increasing trend of PAS (placenta accreta spectrum disorders) incidence is a major health concern as PAS is associated with high maternal morbidity and mortality during cesarean section. Prenatal identification of PAS is crucial for delivery planning and patients management. This study aims to explore whether diffusion-derived vessel density (DDVD) computed from a simple diffusion MRI protocol differs in PAS from normal placenta. METHODS: We enrolled 86 patients with PAS disorders and 40 pregnant women without PAS disorders. Each patient underwent intravoxel incoherent motion (IVIM) MRI sequence with 11 b-values. Placenta diffusion-derived vessel density (DDVD-b0b50) was the signal difference between b = 0 and b = 50 s/mm2 images. DDVD(b0b50) A/N was calculated as [accreta lesion DDVD(b0b50)]/ [normal placenta DDVD(b0b50)]. The correlation between DDVD and gestational age was explored using Spearman rank correlation. Differences of DDVD(b0b50) A/N in patients with normal placentas and with PAS, and in patients with different subtypes of PAS were explored. RESULTS: DDVD was negatively correlated with gestational age (p = 0.023, r = -0.359) in patients with normal placentas. DDVD(b0b50) A/N was significantly higher in patients with PAS (median:1.16, mean: 1.261) than normal placenta (median:1.02, mean: 1.032, p < 0.001) and especially higher in patients with placenta increta (median:1.14, mean: 1.278) and percreta (median: 1.20, mean: 1.396, p < 0.001). CONCLUSION: As a higher DDVD indicates higher physiological volume of micro-vessels in PAS, this study suggests DDVD can be a potential biomarker to evaluate the placenta perfusion.

Perfusion of hepatocellular carcinomas measured by diffusion-derived vessel density biomarker: Higher hepatocellular carcinoma perfusion than earlier intravoxel incoherent motion reports.

Diffusion-derived vessel density (DVDD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to DDVD(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 s/mm2. Pathohistological studies and contrast-enhanced CT/MRI data showed higher blood volume in hepatocellular carcinoma (HCC) relative to native liver tissue. With intravoxel incoherent motion (IVIM) imaging, most authors paradoxically reported a decreased perfusion fraction of HCC relative to the adjacent liver. This study applied DDVD to assess the perfusion of HCC. MRI was performed with a 3.0-T magnet. Diffusion-weighted images with b-values of 0 and 2 s/mm2 were acquired in 72 HCC patients. Thirty-two patients had microvascular invasion (MVI(+)) and 40 patients did not have microvascular invasion (MVI(-)). Fifty-eight patients had Edmondson-Steiner grade I or II HCC, and 14 patients had Edmondson-Steiner grade III or IV HCC. DDVD measurement was conducted on the axial slice that showed the largest HCC size. DDVD(b0b2) T/L = HCC DDVD(b0b2)/liver DDVD(b0b2). DDVD(b0b2) T/L median (95% confidence interval) of all HCCs was 2.942 (2.419-3.522), of MVI(-) HCCs was 2.699 (2.030-3.522), of MVI(+) HCCs was 2.988 (2.423-3.990), of Edmondson-Steiner grade I/II HCCs was 2.873 (2.277-3.465), and of Edmondson-Steiner grade III/IV HCCs was 3.403 (2.008-4.485). DDVD(b0b2) T/L approximately agrees with contrast agent dynamically enhanced CT/MRI literature data, whereas it differs from earlier IVIM study results, where HCC perfusion fraction was paradoxically lower relative to native liver tissue. A weak trend was noted with MIV(+) HCCs had a higher DDVD(b0b2) T/L than that of MVI(-) HCCs, and a weak trend was noted with the poorly differentiated group of HCCs (Edmondson-Steiner grade III and IV) had a higher DDVD(b0b2) T/L than that of the better differentiated group of HCCs (Edmondson-Steiner grade I and II).

Quantitative CT lumbar spine BMD cutpoint value for classifying osteoporosis among older East Asian women should be lower than the value for Caucasians.

For Caucasian women, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) cutpoint value for classifying osteoporosis is 80 mg/ml. At the age of approximate 78 years, US Caucasian women QCT LS BMD population mean is 80 mg/ml, while that of Chinese women and Japanese women is around 50 mg/ml. Correlation analyses show, for Chinese women and Japanese women, QCT LS BMD of 45 mg/ml corresponds to the dual-energy X-ray absorptiometry cutpoint value for classifying osteoporosis. For Chinese and Japanese women, if QCT LS BMD 80 mg/ml is used as the threshold to classify osteoporosis, then the specificity of classifying subjects with vertebral fragility fracture into the osteoporotic group is low, whereas threshold of 45 mg/ml approximately achieve a similar separation for women with and without vertebral fragility fracture as the reports for Caucasian women. Moreover, by using 80mg/ml as the cutpoint value, LS QCT leads to excessively high prevalence of osteoporosis for Chinese women, with the discordance between hip dual-energy X-ray absorptiometry and LS QCT measures far exceeding expectation. Considering the different bone properties and the much lower prevalence of fragility fractures in the East Asian women compared with Caucasians, we argue that the QCT cutpoint value for classifying osteoporosis among older East Asian women will be close to and no more than 50 mg/ml LS BMD. We suggest that it is also imperative the QCT osteoporosis classification criterion for East Asian male LS, and male and female hips be re-examined.

A novel automatic segmentation method directly based on magnetic resonance imaging K-space data for auxiliary diagnosis of glioma.

Background: The use of segmentation architectures in medical imaging, particularly for glioma diagnosis, marks a significant advancement in the field. Traditional methods often rely on post-processed images; however, key details can be lost during the fast Fourier transformation (FFT) process. Given the limitations of these techniques, there is a growing interest in exploring more direct approaches. The adaption of segmentation architectures originally designed for road extraction for medical imaging represents an innovative step in this direction. By employing K-space data as the modal input, this method completely eliminates the information loss inherent in FFT, thereby potentially enhancing the precision and effectiveness of glioma diagnosis. Methods: In the study, a novel architecture based on a deep-residual U-net was developed to accomplish the challenging task of automatically segmenting brain tumors from K-space data. Brain tumors from K-space data with different under-sampling rates were also segmented to verify the clinical application of our method. Results: Compared to the benchmarks set in the 2018 Brain Tumor Segmentation (BraTS) Challenge, our proposed architecture had superior performance, achieving Dice scores of 0.8573, 0.8789, and 0.7765 for the whole tumor (WT), tumor core (TC), and enhanced tumor (ET) regions, respectively. The corresponding Hausdorff distances were 2.5649, 1.6146, and 2.7187 for the WT, TC, and ET regions, respectively. Notably, compared to traditional image-based approaches, the architecture also exhibited an improvement of approximately 10% in segmentation accuracy on the K-space data at different under-sampling rates. Conclusions: These results show the superiority of our method compared to previous methods. The direct performance of lesion segmentation based on K-space data eliminates the time-consuming and tedious image reconstruction process, thus enabling the segmentation task to be accomplished more efficiently.

Differences in pulmonary nodular consolidation and pulmonary cavity among drug-sensitive, rifampicin-resistant and multi-drug resistant tuberculosis patients: the Guangzhou computerized tomography study.

Background: Pulmonary nodular consolidation (PN) and pulmonary cavity (PC) may represent the two most promising imaging signs in differentiating multidrug-resistant (MDR)-pulmonary tuberculosis (PTB) from drug-sensitive (DS)-PTB. However, there have been concerns that literature described radiological feature differences between DS-PTB and MDR-PTB were confounded by that MDR-PTB cases tend to have a longer history. This study seeks to further clarify this point. Methods: All cases were from the Guangzhou Chest Hospital, Guangzhou, China. We retrieved data of consecutive new MDR cases [n=46, inclusive of rifampicin-resistant (RR) cases] treated during the period of July 2020 and December 2021, and according to the electronic case archiving system records, the main PTB-related symptoms/signs history was ≤3 months till the first computed tomography (CT) scan in Guangzhou Chest Hospital was taken. To pair the MDR-PTB cases with assumed equal disease history length, we additionally retrieved data of 46 cases of DS-PTB patients. Twenty-two of the DS patients and 30 of the MDR patients were from rural communities. The first CT in Guangzhou Chest Hospital was analysed in this study. When the CT was taken, most cases had anti-TB drug treatment for less than 2 weeks, and none had been treated for more than 3 weeks. Results: Apparent CT signs associated with chronicity were noted in 10 cases in the DS group (10/46) and 9 cases in the MDR group (10/46). Thus, the overall disease history would have been longer than the assumed <3 months. Still, the history length difference between DS patients and MDR patients in the current study might not be substantial. The lung volume involvement was 11.3%±8.3% for DS cases and 8.4%±6.6% for MDR cases (P=0.022). There was no statistical difference between DS cases and MDR cases both in PN prevalence and in PC prevalence. For positive cases, MDR cases had more PN number (mean of positive cases: 2.63 vs. 2.28, P=0.38) and PC number (mean of positive cases: 2.14 vs. 1.38, P=0.001) than DS cases. Receiver operating characteristic curve analysis shows, PN ≥4 and PC ≥3 had a specificity of 86% (sensitivity 25%) and 93% (sensitivity 36%), respectively, in suggesting the patient being a MDR cases. Conclusions: A combination of PN and PC features allows statistical separation of DS and MDR cases.

East Asians' T-scores for the diagnosis of osteoporosis should be calculated using ethnicity- and gender-specific BMD reference ranges: justifications.

The 2013 ISCD consensus recommended a Caucasian female reference database for T-score calculation in men, which says "A uniform Caucasian (non-race adjusted) female reference database should be used to calculate T-scores for men of all ethnic groups." However, this statement was recommended for the US population, and no position was taken with respect to BMD reference data or ethnicity matching outside of the USA. In East Asia, currently, a Japanese BMD reference database is universally adopted in Japan for clinical DXA diagnosis, while both local BMD and Caucasian BMD reference databases are in use in Mainland China, South Korea, Taiwan, and Singapore. In this article, we argue that an ethnicity- and gender-specific BMD database should be used for T-score calculations for East Asians, and we list the justifications why we advocate so. Use of a Caucasian BMD reference database leads to systematically lower T-scores for East Asians and an overestimation of the prevalence of osteoporosis. Using a female BMD reference database to calculate T-scores for male patients leads to higher T-score values and an underestimation of the prevalence of osteoporosis. Epidemiological evidence does not support using a female BMD reference database to calculate T-scores for men. We also note that BMD reference databases collected in Asia should be critically evaluated for their quality.

Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine.

BACKGROUND: Live attenuated vaccines alter immune functions and are associated with beneficial outcomes. We previously demonstrated that live attenuated yellow fever virus (YFV) vaccine (LA-YF-Vax) dampens T-cell receptor (TCR) signaling in vitro via an RNA-based mechanism. We examined study participants before and after LA-YF-Vax to assess TCR-mediated functions in vivo. METHODS: Serum samples and peripheral blood mononuclear cells (PBMCs) were obtained before and after LA-YF-Vax (with or without additional vaccines) or quadrivalent influenza vaccine. TCR-mediated activation was determined by interleukin 2 release or phosphorylation of the lymphocyte-specific Src kinase. TCR-regulating phosphatase (protein tyrosine phosphatase receptor type E [PTPRE]) expression was also measured. RESULTS: Compared with prevaccination findings, LA-YF-Vax recipient PBMCs demonstrated transient reduction in interleukin 2 release after TCR stimulation and PTPRE levels, unlike in control participants who received quadrivalent influenza vaccine. YFV was detected in 8 of 14 participants after LA-YF-Vax. After incubation of healthy donor PBMCs in serum-derived extracellular vesicles prepared from LA-YF-Vax recipients, TCR signaling and PTPRE levels were reduced after vaccination, even in participants without detectable YFV RNA. CONCLUSIONS: LA-YF-Vax reduces TCR functions and PTPRE levels after vaccination. Extracellular vesicles from serum recapitulated this effect in healthy cells. This likely contributes to the reduced immunogenicity for heterologous vaccines after LA-YF-Vax administration. Identification of specific immune mechanisms related to vaccines should contribute to understanding of the "off-target," beneficial effects of live vaccines.

Revision of the 1994 World Health Organization T-score definition of osteoporosis for use in older East Asian women and men to reconcile it with their lifetime risk of fragility fracture.

The 1994 WHO criterion of a T-score ≤ -2.5 for densitometric osteoporosis was chosen because it results in a prevalence commensurate with the observed lifetime risk of fragility fractures in Caucasian women aged ≥ 50 years. Due to the much lower risk of fragility fracture among East Asians, the application of the conventional WHO criterion to East Asians leads to an over inflated prevalence of osteoporosis, particularly for spine osteoporosis. According to statistical modeling and when a local BMD reference is used, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.7 for Hong Kong Chinese women. Using radiographic osteoporotic vertebral fracture as a surrogate clinical endpoint, we empirically demonstrated that a femoral neck T-score of -2.77 for Chinese women was equivalent to -2.60 for Italian women, a spine T-score of -3.75 for Chinese women was equivalent to -2.44 for Italian women, and for Chinese men a femoral neck T-score of -2.77 corresponded to spine T-score of -3.37. For older Chinese men, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.2. With the BMD reference published by IKi et al. applied, T-score of femoral neck, total hip, and spine of -2.75, -3.0, and -3.9 for Japanese women will be more in line with the WHO osteoporosis definition. The revised definition of osteoporosis cutpoint T-scores for East Asians will allow a more meaningful international comparison of disease burden.