Survival outcomes of young-age female patients with early breast cancer: an international multicenter cohort study.

BACKGROUND: The incidence of breast cancer among young Asian women is increasing, yet they remain underrepresented in global data. We analyzed the epidemiology and outcomes of Asian patients with breast cancer <40 years old across different subtypes to identify their clinical unmet needs. PATIENTS AND METHODS: Female patients aged ≥20 years diagnosed with early breast cancer were analyzed from the prospective cohort of the Asian Breast Cancer Cooperative Group (ABCCG). For comparison, data from the Surveillance, Epidemiology, and End Results Program (SEER) cancer registry were used. Patients were categorized into three age groups: young (<40 years), alleged premenopausal mid-age (40-49 years), and alleged postmenopausal (aged ≥50 years). Multivariable Cox proportional hazards models for survival were adjusted for subtypes, histologic grade, T stage, nodal status, and study centers. RESULTS: A total of 45 021 patients with breast cancer from Asian study centers, 496 332 SEER-White patients, and 18 279 SEER-Asian patients were included in the analysis. The median age at diagnosis was younger in the Asian cohort (51 years) compared with SEER-Whites (62 years) and SEER-Asians (58 years; P < 0.0001). In the young-age group, hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer was more prevalent among Asians and SEER-Asians compared with SEER-Whites (61.2% and 59.8% versus 54.7%). In the Asian population, young patients with HR+/HER2- breast cancer exhibited significantly inferior overall survival than the mid-age group (6-year overall survival 94.4% versus 96.6%; mid-age to young-age group hazard ratio 0.62; P < 0.001). Similarly, young patients in SEER-Whites showed an earlier decline in survival compared with the mid-age group (89.1% versus 94.0%; P < 0.001). CONCLUSION: ABCCG-Asian patients with breast cancer <40 years old with HR+/HER2- subtypes were more likely to have worse survival outcomes than their mid-age counterparts. Our study highlights the poorer prognosis of young patients and underscores the need for a tailored therapeutic approach, such as ovarian function suppression, particularly considering ethnic factors.

Unveiling attenuation structures in the northern Taiwan volcanic zone.

This cutting-edge study delves into regional magmatism in northern Taiwan through advanced 3-D P- and S-wave frequency-dependent attenuation tomography. Positioned at the dynamic convergence boundary between the Philippine Sea Plate and the Eurasian Plate, Taiwan experiences moderate earthquakes and intriguing volcanic activity, with a focus on the Tatun volcano group. Employing the Formosa seismic array for high-resolution results, our research identifies high-attenuation anomalies (low Q) beneath the northern Taiwan volcanic zone (NTVZ) and offshore submarine volcanoes, indicative of potential hydrothermal activities and magma reservoirs at varying depths. Additionally, we explore low-attenuation anomalies (high Q) in the forearc region of the Ryukyu subduction zone, suggestive of partial saturation linked to serpentinization processes resulting from seawater infiltration or forearc mantle hydration. These findings shed light on the complex geological features and provide essential insights into the crustal properties of northern Taiwan, contributing to a deeper understanding of its magmatic evolution and tectonic processes.

Effect of Taiwan's Diabetes Shared Care Program on the risk of periprosthetic joint infection after total joint arthroplasty in patients with type 2 diabetes mellitus: an eight-year population-based study.

BACKGROUND: Periprosthetic joint infection (PJI) is a significant post-arthroplasty complication for diabetic patients, with uncontrolled diabetes identified as a PJI risk factor. Taiwan's Diabetes Shared Care Program (DSCP) was established for holistic diabetes care. AIM: To evaluate the DSCP's impact on PJI incidence and patients' medical costs. METHODS: Data were analysed from Taiwan's National Health Insurance Research Database from 2010 to 2020, focusing on type 2 diabetes mellitus (DM) patients who had undergone arthroplasty. The study group involved DSCP participants, while a comparison group comprised non-participants with matched propensity scores for age, sex, and comorbidities. The primary outcome was the PJI incidence difference between the groups; the secondary outcome was the medical expense difference. FINDINGS: The study group consisted of 11,908 type 2 DM patients who had arthroplasty and joined the DSCP; PJI occurred in 128 patients. Among non-participants, 184 patients had PJI. The PJI incidence difference between the groups was statistically significant (1.07% vs 1.55%). The study group's medical costs were notably lower, regardless of PJI incidence. Multivariate regression showed higher PJI risk in patients in comparison group, aged >70 years, male, or who had obesity, anaemia. CONCLUSION: The study indicates that DSCP involvement reduces PJI risks and decreases annual medical costs for diabetic patients after arthroplasty. Consequently, the DSCP is a recommendable option for such patients who are preparing for total joint arthroplasty.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.

Clinical Efficacy of Multidomain Interventions among Multimorbid Older People Stratified by the Status of Physio-Cognitive Declines: A Secondary Analysis from the Randomized Controlled Trial for Healthy Aging.

OBJECTIVES: To investigate the clinical efficacy of integrated multidomain intervention among community-living older adults with multimorbidity and physio-cognitive decline syndrome (PCDS). DESIGN, SETTING AND PARTICIPANTS: This is the secondary analysis from a randomized controlled trial that data of 340 participants with Montreal Cognitive Assessment (MoCA) scores≥18 were excerpted for analysis. INTERVENTION: Sixteen 2-hour sessions per year were provided for participants, including physical exercise, cognitive training, dietician education and individualized integrated care for multimorbidity. MEASUREMENTS: Handgrip strength, 6-m walking speed, MoCA (total score and sub-domains), Cardiovascular Health Study (CHS) frailty score, quality of life, and serum biochemistry biomarkers. RESULTS: Overall, 96/340 (28.2%) of all participants have PCDS, and the integrated multidomain intervention significantly improved global cognitive performance (overall difference 1.1, 95% CI 0.4 - 1.8, p=0.003), and domains of concentration (overall difference 0.3, 95%CI 0.1 - 0.5, p=0.011), language (overall difference 0.2, 95%CI 0.1 - 0.3, p=0.006), abstract thinking (overall difference 0.1, 95%CI 0.0 - 0.3, p=0.027), and orientation(overall difference 0.2, 95%CI 0.0 - 0.4, p=0.013) across all timepoints among those with PCDS. Besides, interventions also significantly reduced frailty score among those with cognitive impairment no dementia (overall difference -0.3, 95%CI -0.5 - -0.1, p=0.011) and mobility impairment no disability (overall difference -0.3, 95%CI -0.4 - -0.1, p=0.004). and improved quality of life at domain of physical role limitation among those with PCDS (overall difference 5.3, 95%CI 0.3 - 10.4, p=0.038). CONCLUSIONS: The integrated multidomain lifestyle intervention plus multimorbidity management significantly improved cognitive function, and enhanced quality of life among older adults with multimorbidity and PCDS in the communities.

Relapse patterns of two-jaw surgical correction in patients with skeletal Class III malocclusion and different vertical facial types.

The aim of this study was to evaluate postoperative relapse after the surgical correction of skeletal Class III deformities of various facial patterns as a guide to surgical planning. A retrospective cohort study of 90 consecutive patients with skeletal Class III malocclusion who underwent bimaxillary surgery was performed. The surgical outcomes and postoperative stability were compared. The primary predictor variable was vertical facial type, which was classified into three groups according to the Frankfort mandibular plane angle (FMA). The primary outcome of angular and linear measurements was obtained using serial cone beam computed tomography scans obtained at time points of preoperative, 1 week after surgery, and orthodontic debonding. No significant difference in skeletal relapse was observed in patients with the different vertical facial types. The mandible displayed a forward and upward relapse in all three groups postoperatively. The patients with a low FMA exhibited a more consistent mandibular relapse pattern than those with a normal or high FMA. These findings suggest that bimaxillary surgery is clinically stable for mandibular prognathism regardless of the vertical facial pattern. However, 1-1.5 mm of overcorrection in the mandible setback should be considered in patients with a low FMA, because of the greater facial depth and consistent forward and upward mandibular relapse pattern.

Chondroitin Sulfate Enhances Proliferation and Migration via Inducing ß-Catenin and Intracellular ROS as Well as Suppressing Metalloproteinases through Akt/NF-κB Pathway Inhibition in Human Chondrocytes.

BACKGROUND: Chondroitin sulfate (CS) is found in humans' cartilage, bone, cornea, skin, and arterial wall. It consists of the foundation substance in the extracellular matrix (ECM) of connective tissue. The oral supplement form of CS is clinically used in treating osteoarthritis (OA). METHODS: Cell migration was observed by the transwell assay. The EMT, Akt/IKK/IκB pathways, TIMPs, collagen and MMPs in cell lysate were determined by Western blotting. The expression of MMP activity was determined by gelatin zymography. The production of reactive oxygen species (ROS) was determined by using a fluorescence spectrophotometer. RESULTS: In the current report, we demonstrated that CS can increase the cell proliferation and migration of chon-001 chondrocytes. Treatment with CS induced the epithelial-mesenchymal transition and increased the expression of type II collagen and TIMP-1/TIMP2 and inhibited the expressions and activities of metalloproteinase-9 (MMP-9) and metalloproteinase-2 (MMP-2). The phosphorylation of Akt, IκB kinase (IKK), IκB and p65 was decreased by CS. CS treatment resulted in ß-catenin production and XAV939, a ß-catenin inhibitor, and inhibited the cell proliferation by CS treatment. In addition, also significantly induced intracellular ROS generation. Treatment with antioxidant propyl gallate blocked cell migration induced by CS. CONCLUSION: We demonstrated that CS induced cell proliferation and migration of chondrocytes by inducing ß-catenin and enhancing ROS production. Moreover, our studies demonstrated that CS can increase the activity of chondrocytes and help patients with osteoarthritis to restore cartilage function.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients with renal dysfunction.

OBJECTIVE: This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. DESIGN: We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and <60 ml/min/1.73 m2 or on dialysis and by the propensity score from August 2006 to May 2015. The odds ratio of poor functional outcome (modified Rankin Scale ≥2) was calculated for patients with tPA treatment (N = 705), compared to those without tPA treatment (N = 2820), by eGFR levels, at 1, 3 and 6 months after ischemic stroke. We also evaluated the risks of intracerebral hemorrhage, upper gastrointestinal bleeding, mortality, between the two groups by eGFR levels. RESULTS: Among patients with eGFR levels of <60 ml/min/1.73 m2, tPA therapy reduced the odds ratio of poor functional outcome to 0.60 (95% confidence interval = 0.42-0.87) at 6 months after ischemic stroke. The tPA therapy was not associated with increased overall risk of upper gastrointestinal bleeding, but with increased risk of intracerebral hemorrhage. The low eGFR was not a significant risk factor of intracerebral hemorrhage among ischemic stroke patients receiving tPA treatment. CONCLUSIONS: tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

Predictive Validity of the Physical Resilience Instrument for Older Adults (PRIFOR).

This study aimed at evaluating the predictive ability of the Physical Resilience Instrument for Older Adults (PRIFOR) for the recovery of frailty, activity of daily living (ADL), and quality of life in older adults suffering from acute health stressors. The longitudinal study was adopted and patients aged 65 and older with Clinical Frailty Scale (CFS) scores between 4 and 6 were included. The PRIFOR was used to assess physical resilience at baseline. Katz ADL, CFS and EuroQoL 5-dimension Questionnaire (EQ5D) scores were all assessed at baseline and one month after discharge. The mean age of the 192 participants was 76.29 ± 6.53 years, and 50.5% were female. After adjusting for the baseline condition, the PRIFOR was only significantly associated with the CFS (ß=-0.183, p<0.001) at one month after discharge. Our study results provide evidence of the predictive capacity of the PRIFOR for recovery from frailty.

[Genetic analysis of 45 patients with suspected Lynch syndrome using next-generation sequencing].

Objective: To evaluate the value of next generation sequencing (NGS) in the genetic testing of Lynch syndrome. Methods: Immunohistochemical method was used to detect the expressions of DNA mismatch repair (MMR) proteins, including MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) in colorectal cancer, gastric cancer and endometrial cancer tissues collected from Shandong Provincial Hospital between 2016 and 2018. The genomic DNA of 45 patients who were suspected with Lynch syndrome was extracted from non-cancerous tissue paraffin samples, which were postoperatively confirmed by microscope. The mutations of 12 genes including MLH1 and MSH2 were detected using NGS. The germline mutant sites and significance were analyzed by bioinformatics technology and further confirmed by using Sanger sequencing. Results: The immunohistochemical results showed that the 45 cases of suspected Lynch syndrome included 22 cases of MLH1 and PMS2 deficient expression, 16 cases of MLH2 and MSH6 deficient expression, and 7 cases of MMR proteins normal expression. The NGS result showed that 28 cases of adjacent sample from colon cancer patients included 4 cases of MLH1 pathogenic mutation, 1 case of suspected MLH1 mutation, 2 cases of MLH2 pathogenic mutation, 2 cases of suspected MLH2 mutation. No MMR gene mutation was found in adjacent samples of 6 cases of rectal cancer, 6 cases of gastric cancer and 7 cases of colorectal cancer with MMR normal expression. One case of MLH1 or MHL2 pathogenic mutation and one case of MLH1 suspected mutation was detected in adjacent samples of 5 cases of endometrial cancer. Moreover, NGS also detected many other genes mutations and unreported gene mutation sites. Pathogenic and suspected MLH1 and MSH2 mutations were verified by Sanger sequencing. Conclusions: High-throughput NGS is a quick, accurate and reliable technique to identify gene variants in suspected Lynch syndrome patients. It has a wide application prospect for gene testing of tumors associated with Lynch syndrome.

Lifetime risks of hip fracture in patients with type 2 diabetic: Taiwan Diabetes Study.

This study is to estimate the lifetime risks of hip fracture in Chinese patients with type 2 diabetes. INTRODUCTION: The lifetime risks of hip fracture have not been reported across the age spectrum in male adults and female adults with type 2 diabetes. METHODS: A retrospective cohort study was conducted on 25275 men and 27953 women with type 2 diabetes aged 30-100 years old and participated in the National Diabetes Case Management Program in 2002-2004 in Taiwan. Sociodemographic factors, biomarkers, and comorbidity at the baseline and hip fracture events were analyzed with Cox proportional hazards regression models with age as the time scale. RESULTS: Significant differences in the lifetime risks of hip fracture were observed between men and women with type 2 diabetes. The cumulative lifetime incidences (%) of hip fracture at 50, 60, 65, 70, 75, 80, and 85 years old for men were 0.11, 0.40, 0.84, 1.84, 3.82, 8.53, and 16.72, respectively. The corresponding lifetime incidences (%) for women at 50, 60, 65, 70, 75, 80, and 85 years old were 0.05, 0.50, 1.36, 3.89, 9.56, 21.19, and 35.45, respectively. With competing risks, the significant multivariate-adjusted hazard ratio of developing hip fracture included smoking, alcohol drinking, duration of diabetes, type of oral hypoglycemic drugs use (no medication, sulfonylurea only, thiazolidinediones (TZD) only or TZD plus others, other single or multiple oral agents, insulin use, insulin plus oral hypoglycemic drug use), loop diuretics use, use of corticosteroids, normal weight or underweight, hyperlipidemia, and chronic obstructive pulmonary disease. CONCLUSIONS: The gender differences in lifetime hip fracture risk were significant. Thiazolidinediones and insulin use are factors with the greater magnitude of strength of association among those significantly associated with hip fracture.

FKRP-dependent glycosylation of fibronectin regulates muscle pathology in muscular dystrophy.

The muscular dystrophies encompass a broad range of pathologies with varied clinical outcomes. In the case of patients carrying defects in fukutin-related protein (FKRP), these diverse pathologies arise from mutations within the same gene. This is surprising as FKRP is a glycosyltransferase, whose only identified function is to transfer ribitol-5-phosphate to α-dystroglycan (α-DG). Although this modification is critical for extracellular matrix attachment, α-DG's glycosylation status relates poorly to disease severity, suggesting the existence of unidentified FKRP targets. Here we reveal that FKRP directs sialylation of fibronectin, a process essential for collagen recruitment to the muscle basement membrane. Thus, our results reveal that FKRP simultaneously regulates the two major muscle-ECM linkages essential for fibre survival, and establishes a new disease axis for the muscular dystrophies.

Contamination of chicken carcasses and the abattoir environment with Listeria monocytogenes in Taiwan.

1. The following study provides the first data on the detection and types of Listeria monocytogenes isolated from broiler chickens during processing and from six Taiwanese abattoir environments.2. Listeria monocytogenes was not detected in any cloacal (n = 120) or environmental (n = 256) samples collected before and during processing, indicating that faecal material and the environment of abattoirs were not important sources of L. monocytogenes for poultry carcases. However, 28 of 246 (11.4%; 95% CI: 7.7-16.0) rinse samples collected from carcases post-evisceration from three abattoirs were positive for L. monocytogenes.3. The only serotypes detected were 1/2a (82.1%; 95% CI: 63.1-93.9) and 1/2b (14.3%; 95% CI: 4.0-32.7), with 3.6% (95% CI: 0.1-18.3) non-typable isolates.4. Characterisation by Pulsed Field Gel Electrophoresis (PFGE) identified five PFGE types, confirming cross-contamination with L. monocytogenes during evisceration, chilling and post-chilling.5. These findings highlight the potential for cross-contamination to occur through direct contact between carcases, especially whilst in chilling tanks.

Novel REST Truncation Mutations Causing Hereditary Gingival Fibromatosis.

Hereditary gingival fibromatosis (HGF) is a rare genetic disorder featured by nonsyndromic pathological overgrowth of gingiva. The excessive gingival tissues can cause dental, masticatory, and phonetic problems, which impose severe functional and esthetic burdens on affected individuals. Due to its high recurrent rate, patients with HGF have to undergo repeated surgical procedures of gingival resection, from childhood to adulthood, which significantly compromises their quality of life. Unraveling the genetic etiology and molecular pathogenesis of HGF not only gains insight into gingival physiology and homeostasis but also opens avenues for developing potential therapeutic strategies for this disorder. Recently, mutations in REST (OMIM *600571), encoding a transcription repressor, were reported to cause HGF (GINGF5; OMIM #617626) in 3 Turkish families. However, the functions of REST in gingival homeostasis and pathogenesis of REST-associated HGF remain largely unknown. In this study, we characterized 2 HGF families and identified 2 novel REST mutations, c.2449C>T (p.Arg817*) and c.2771_2793dup (p.Glu932Lysfs*3). All 5 mutations reported to date are nonsenses or frameshifts in the last exon of REST and would presumably truncate the protein. In vitro reporter gene assays demonstrated a partial or complete loss of repressor activity for these truncated RESTs. When coexpressed with the full-length protein, the truncated RESTs impaired the repressive ability of wild-type REST, suggesting a dominant negative effect. Immunofluorescent studies showed nuclear localization of overexpressed wild-type and truncated RESTs in vitro, indicating preservation of the nuclear localization signal in shortened proteins. Immunohistochemistry demonstrated a comparable pattern of ubiquitous REST expression in both epithelium and lamina propria of normal and HGF gingival tissues despite a reduced reactivity in HGF gingiva. Results of this study confirm the pathogenicity of REST truncation mutations occurring in the last exon causing HGF and suggest the pathosis is caused by an antimorphic (dominant negative) disease mechanism.

Unveiling Tatun volcanic plumbing structure induced by post-collisional extension of Taiwan mountain belt.

The Tatun Volcanic Group (TVG) is proximal to the metropolis of Taipei City (population of ca. 7 million) and has long been a major concern due to the potential risks from volcanic activity to the population and critical infrastructure. While the TVG has been previously considered a dormant or extinct volcano, recent evidence suggests a much younger age of the last eruption event (~ 6000 years) and possible existence of a magma reservoir beneath the TVG. However, the location, dimension, and detailed geometry of the magma reservoir and plumbing system remains largely unknown. To examine the TVG volcanic plumbing structure in detail, the local P-wave travel time data and the teleseismic waveform data from a new island-wide Formosa Array Project are combined for a 3D tomographic joint inversion. The new model reveals a magma reservoir with a notable P-wave velocity reduction of 19% (ca. ~ 19% melt fraction) at 8-20 km beneath eastern TVG and with possible northward extension to a shallower depth near where active submarine volcanoes that have been detected. Enhanced tomographic images also reveal sporadic magmatic intrusion/underplating in the lower crust of Husehshan Range and northern Taiwan. These findings suggest an active volcanic plumbing system induced by post-collisional extension associated with the collapse of the orogen.

Glycaemic control for painful diabetic peripheral neuropathy is more than fasting plasma glucose and glycated haemoglobin.

BACKGROUND: The relationship between postprandial hyperglycaemia and diabetic peripheral neuropathy (DPN), whether painful or painless, has yet to be determined. Thus, the aim of this study was to investigate the relationship in patients with type 2 diabetes (T2D). METHODS: This cross-sectional study was conducted in adults with T2D between January and October 2013. Blood samples were collected after overnight fasting every 3 months prior to enrolment. For this study, increased postprandial glycaemic exposure was defined as high glycated haemoglobin (HbA1c) and near-normal mean fasting plasma glucose (FPG) levels. Both painless and painful DPN were evaluated using two validated tools, the Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique 4 (DN4) questionnaire. RESULTS: This study included 1040 participants with mean FPG levels<140mg/dL, 535 of which were<126mg/dL. Of these patients, 200/1040 (19.2%) and 105/535 (19.6%) had DPN. Multivariate analysis demonstrated that higher HbA1c levels (≥7%) did not increase risk of painless DPN, but did significantly increase risk of painful DPN in T2D patients with FPG<140mg/dL and<126mg/dL, with corresponding odds ratios of 2.49 and 3.77 (95% confidence intervals: 1.09-5.71 and 1.20-11.79), respectively, after adjusting for demographic factors, diabetes-related variables and comorbidities. CONCLUSION: This study is the first to reveal that increased postprandial glycaemic exposure, as assessed by high HbA1c and near-normal FPG levels, is associated with an increased risk of painful DPN in adults with T2D.

Effect of compression fracture on trabecular bone score at lumbar spine.

Bone mineral density (BMD) may be increased due to vertebral compression fractures (VCF). Our study showed trabecular bone scores (TBS) was less affected than BMD by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk. INTRODUCTION: Trabecular bone score (TBS), a noninvasive tool estimating bone microarchitecture, provides complementary information to lumbar spine bone mineral density (BMD). Lumbar spine BMD might be increased due to both degenerative disease and vertebral compression fractures (VCF). Lumbar spine TBS has been confirmed not influenced by osteoarthrosis, but the effects of VCF are still not been well evaluated. This study aimed to investigate whether lumbar spine TBS was affected by fractured vertebrae. METHODS: We studied postmenopausal women and men above 50 years old who underwent DXA between January 1, 2017, and May 31, 2019. By calculating the difference of BMD and TBS between L1 and the mean of L2-3, the study compared the difference of values between the control group and fracture group to determine the effects of fractured vertebrae on BMD and TBS. RESULTS: A total of 377 participants were enrolled with 202 in the control group (157 females; age: 68.06 ± 6.47 years) and 175 in the fracture group (147 females; age: 71.71 ± 9.44 years). The mean BMD of the L1 vertebrae in the fracture group was significantly higher than that in the control group (p < 0.0001). There was no significant difference between the mean differences of TBS between L1 and the means of L2-3 vertebrae in the control group and the most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity. CONCLUSION: Lumbar spine TBS, unlike BMD, is less affected by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk.

Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is strongly associated with favorable outcome. We examined the utility of serial circulating tumor DNA (ctDNA) testing for predicting pCR and risk of metastatic recurrence. PATIENTS AND METHODS: Cell-free DNA (cfDNA) was isolated from 291 plasma samples of 84 high-risk early breast cancer patients treated in the neoadjuvant I-SPY 2 TRIAL with standard NAC alone or combined with MK-2206 (AKT inhibitor) treatment. Blood was collected at pretreatment (T0), 3 weeks after initiation of paclitaxel (T1), between paclitaxel and anthracycline regimens (T2), or prior to surgery (T3). A personalized ctDNA test was designed to detect up to 16 patient-specific mutations (from whole-exome sequencing of pretreatment tumor) in cfDNA by ultra-deep sequencing. The median follow-up time for survival analysis was 4.8 years. RESULTS: At T0, 61 of 84 (73%) patients were ctDNA positive, which decreased over time (T1: 35%; T2: 14%; and T3: 9%). Patients who remained ctDNA positive at T1 were significantly more likely to have residual disease after NAC (83% non-pCR) compared with those who cleared ctDNA (52% non-pCR; odds ratio 4.33, P = 0.012). After NAC, all patients who achieved pCR were ctDNA negative (n = 17, 100%). For those who did not achieve pCR (n = 43), ctDNA-positive patients (14%) had a significantly increased risk of metastatic recurrence [hazard ratio (HR) 10.4; 95% confidence interval (CI) 2.3-46.6]; interestingly, patients who did not achieve pCR but were ctDNA negative (86%) had excellent outcome, similar to those who achieved pCR (HR 1.4; 95% CI 0.15-13.5). CONCLUSIONS: Lack of ctDNA clearance was a significant predictor of poor response and metastatic recurrence, while clearance was associated with improved survival even in patients who did not achieve pCR. Personalized monitoring of ctDNA during NAC of high-risk early breast cancer may aid in real-time assessment of treatment response and help fine-tune pCR as a surrogate endpoint of survival.