Reasonable Cut-off Value Research Articles

Cut-off values for estimated cardiorespiratory fitness in terms of physical functioning among middle-aged to older adults.

Cardiorespiratory fitness is linked to various health outcomes. This study aimed to establish cut-off values for estimated cardiorespiratory fitness associated with poor physical functioning in middle-aged to older adults. A total of 2638 participants (1083 males), aged 40-69 years, performed a 6-min walking test (6MWT) to estimate cardiorespiratory fitness (VO<inf>2max)</inf> and completed a health-related questionnaire. Physical functioning was assessed using four outcomes: perceived health, perceived fitness, difficulties in 2-km walking, and difficulties in climbing several stairs. Receiver operator characteristics (ROC) curves were used to determine cut-off values for estimated VO<inf>2max</inf> and 6MWT distance linked to poor physical functioning based on the four outcomes. Analyses were done separately for males and females, and for 40- to 49-, 50- to 59-, and 60- to 69-year-old groups. Multinomial regression was used to analyze differences between fitness thirds in outcome variables. ROC analyses were significant for all outcomes (AUC 0.686-0.834, P<0.001). In the total group, cut-off values for estimated VO<inf>2max</inf> were 29.9-30.2 mL/kg/min, and for walking distance, 588.0-599.5 m. Cut-off values decreased with age, and mean differences between males and females were 3.3 mL/kg/min and 33 m. All cut-off values were within ±1.3 mL/kg/min of the lower fitness tertile. The odds ratios of having poor physical functioning in the middle and high fitness thirds were less than 0.50 compared to low fitness third. VO<inf>2max</inf> of 30 mL/kg/min and 600-m walking distance seemed reasonable cut-off values for poor physical functioning. Exceeding the currently proposed thresholds is a desirable goal to avoid consequences of insufficient fitness.

Usefulness of health checkup-based indices in identifying metabolic dysfunction-associated steatotic liver disease.

The application of indices in the context of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unexplored. We aimed to validate the ability of alanine aminotransferase (ALT), fatty liver index (FLI), and hepatic steatosis index (HSI) to identify MASLD during health checkups. We recruited 627 participants and utilized their health checkup data and ultrasound to assess the potential of using ALT, FLI, and HSI as indices for MASLD; this was indicated by the area under the curve (AUC) and restricted cubic spline (RCS) model. The optimal, rule-out (sensitivity ≥90%), and rule-in (specificity ≥90%) cutoff values of each index for identifying MASLD were reported. Among participants with a median age of 46 years, the prevalence of MASLD was 28% in total (38% in males and 18% in females). RCS models confirmed a linear association between indices and MASLD. ROC analyses indicated that the AUC of ALT in identifying MASLD was 0.79 for the total cohort, 0.81 for males, and 0.69 for females. The optimal, rule-out, and rule-in cutoff values for ALT were 21, 13, and 29, respectively. Similarly, the AUC of FLI/HSI in identifying MASLD was 0.90/0.88 for the total cohort, 0.86/0.85 for males, and 0.93/0.90 for females. Considering the reference cutoff values, distinct cutoff values were observed between the sexes for FLI, while HSI had similar cutoff values. This study demonstrated that ALT > 30 IU/L is a reasonable cutoff value to rule-in MASLD. ALT, FLI, and HSI are reliable indices for identifying MASLD during health checkups.

Evaluation of the role of diffusion-weighted imaging in various pancreatic pathologies

Background: Diffusion-weighted imaging (DWI) can confidently characterize the nature of a lesion. “Apparent diffusion coefficient” (ADC) has a role in evaluating malignant lesions of the pancreas when conventional sequences appear normal. Aims and Objectives: The aim of the study was to determine the role of DWI and ADC to differentiate benign from malignant pancreatic lesions. Materials and Methods: An observational study was carried out on 75 participants with a suggestion of pancreatic pathologies at a tertiary care institute. Twenty-five participants, who had normal parenchyma of the pancreas, were taken as controls. Magnetic resonance imaging protocol was done, including DWI and ADC. Data analysis was done using coGuide software. ADC was the primary outcome of interest. Results: Out of the 75 cases, 76.9 % (n=60) were males. 15.4 % (n=9) of pathologies were malignant. A significant decrease of ADC values in subjects with acute diffuse pancreatitis (1.12×10-3), acute on chronic pancreatitis (1.14×10-3), chronic pancreatitis (1.32×10-3) as well as adenocarcinoma pancreas (0.92×10-3) was seen in comparison to the controls (1.41×10-3). ADC values for acute pancreatitis, chronic pancreatitis, and acute on chronic pancreatitis were significantly higher than malignancy. Conclusion: DWI and ADC is a useful tools complementing conventional MR imaging and other imaging modalities in characterizing pancreatic pathologies. Mean ADC values of various pancreatic diseases can be determined without major overlap and a reasonable cutoff value can be obtained for differentiating benign and malignant lesions.

Relevance of dedicated multiple sclerosis serum biomarkers in predicting contrast enhancement with gadolinium: Results from the REDUCE-GAD trial.

The presence of contrast enhancement (CE) on magnetic resonance imaging (MRI) is one of the principal criteria for diagnosis and disease activity of multiple sclerosis (MS). Therefore, MS patients are frequently exposed to contrast agents, which may cause deposition in the brain, restricting its use in repeat examinations. Thus, serum biomarkers may be valuable as surrogate parameters to evaluate MS activity. REDUCE-GAD was a prospective, multicentric, biobanking study to determine whether established serum markers (neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], tau protein, ubiquitin-carboxyl-terminal-hydrolase (UCH-L1), S100B and matrix-metalloproteinase 9 [MMP9]) are predictive of CE-positive MRI lesions. Blood samples were obtained from patients undergoing MRI 5 days before or after collection. Patients (N = 102) from four different centers with confirmed MS or related disorders were included; n = 57 (55.9%) showed CE on MRI versus n = 45 (44.1%) without CE. Only higher NfL values indicated CE (odds ratio [OR] 1.05; 95% CI 1.0-1.09) and were correlated with number (ρ = 0.47; p < 0.001) and diameter of CE lesions (ρ = 0.58; p < 0.001). Nfl Z-scores improved diagnostic accuracy (OR 1.52; 95% CI 1.06-2.18). Receiver operator characteristic analysis revealed a reasonable cut-off value for NfL at 14.1 pg/mL (sensitivity 49.1%; specificity 82.2%; positive predictive value 77.8%; negative predictive value 56.0%). NfL ≥59.2 pg/mL was exclusively observed in patients with CE. Evaluation of several possible serum biomarkers for CE in MS patients provided the most robust results for NfL, particularly as Z-scores. Following further evaluation, biomarkers may help stratify the application of contrast agents for brain imaging in MS patients.

Round-Robin test for the histological diagnosis of acute colonic Graft-versus-Host disease validating established histological criteria and grading systems

Histomorpholgy is one of the mainstays of acute Graft-versus-host disease (GvHD) diagnosis. However, concerns about reproducibility and the most appropriate grading system question its usefulness. Our aim was to assess histomorphological parameters and previously reported grading systems for GvHD regarding reproducibility and validity. Moreover, we propose that sum scores, derived by combining separately scored morphological parameters into a total score, might provide a simplified but equally effective means to grade GvHD. A total of 123 colon biopsies were assessed across four pathologists for intestinal GvHD using a Round-Robin test and results were correlated with clinical findings. Interobserver reproducibility was high for histological parameters that were evaluated as indicators of acute GvHD. Published grading systems were moderately reproducible (ICC 0.679–0.769) while simplified sum scores, in comparison, showed better interrater reliability (ICC 0.818–0.896). All grading systems and sum scores were associated with clinical signs of GvHD and in part with therapy response and survival. However, they were not able to stratify patients according to the clinical severity of GvHD. In a hot-spot analysis 1 crypt apoptotic body (CAB) in 10 crypts was a reasonable cut-off value for minimal diagnostic criteria of GvHD. In conclusion, histology can contribute to the diagnosis of GvHD and is reproducible. Published grading systems are able to reflect clinical findings as are simplified sum scores, which showed improved reproducibility and might be easier to handle as they are based on adding up histological parameters rather than transferring histological findings into a separate grading system. Sum scores will have to be further tested in a prospective setting.

Let the data speak about the cut-off values for multidimensional index: Classification of human development index with machine learning

The Human Development Index (HDI) classification is essential as it relates to international aid policies and business strategies. Although the existing literature has criticized the arbitrariness of cut-off values of the HDI, few proposed an ideal approach to overcome this drawback. This paper first employs the unsupervised machine learning techniques, the K-means clustering and Partitioning Around Medoids algorithms, to cluster the HDI and offers more reasonable cut-off values for classifying countries in combination with the current HDI calculation method. The results indicate that we can group the countries worldwide into three clusters, given the 2018 HDI dataset. We suggest cut-off values of 0.65 and 0.85 to classify low, medium, and high human development countries. This paper provides a new perspective to classifying the HDI based on the similarity of countries’ development but not subjective judgments.

Plasma Fibulin-5 Levels as an Independent Predictor of a Poor Outcome after an Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is a poor-outcome disease with a delayed neurological exacerbation. Fibulin-5 (FBLN5) is one of matricellular proteins, some of which have been involved in SAH pathologies. However, no study has investigated FBLN5's roles in SAH. This study was aimed at examining the relationships between serially measured plasma FBLN5 levels and neurovascular events or outcomes in 204 consecutive aneurysmal SAH patients, including 77 patients (37.7%) with poor outcomes (90-day modified Rankin Scale 3-6). Plasma FBLN5 levels were not related to angiographic vasospasm, delayed cerebral ischemia, and delayed cerebral infarction, but elevated levels were associated with severe admission clinical grades, any neurological exacerbation and poor outcomes. Receiver-operating characteristic curves indicated that the most reasonable cut-off values of plasma FBLN5, in order to differentiate 90-day poor from good outcomes, were obtained from analyses at days 4-6 for all patients (487.2 ng/mL; specificity, 61.4%; and sensitivity, 62.3%) and from analyses at days 7-9 for only non-severe patient (476.8 ng/mL; specificity, 66.0%; and sensitivity, 77.8%). Multivariate analyses revealed that the plasma FBLN5 levels were independent determinants of the 90-day poor outcomes in both all patients' and non-severe patients' analyses. These findings suggest that the delayed elevation of plasma FBLN5 is related to poor outcomes, and that FBLN5 may be a new molecular target to reveal a post-SAH pathophysiology.

Predictive Markers of Crohn's Disease in Small Bowel Capsule Endoscopy: A Retrospective Study of Small Bowel Capsule Endoscopy.

To distinguish between functional gastrointestinal disorders like irritable bowel syndrome (IBS) and mild small bowel Crohn′s disease (CD) can be a burden. The diagnosis of CD often requires small bowel capsule endoscopy (SBCE). The main goal of this research was to find predictive markers to rule out clinically significant small bowel CD without SBCE. A retrospective study of 374 patients who underwent SBCE for suspected small bowel CD in Turku University Hospital in 2012–2020 was conducted. We gathered the patient′s laboratory, imaging and endoscopic findings at the time of SBCE. SBCE findings were graded along CECDAI (Capsule Endoscopy Crohn’s Disease Activity Index)-scoring system. Fecal calprotectin (FC), serum albumin and ESR were significantly different with patients diagnosed with CD and those with not. Hb and CRP had no significant differences between the two groups. Sensitivity, specificity, PPV and NPV for FC < 50 ug/g were 96.4%, 19.6%, 34.6% and 92.5% and for CECDAI (cut-off value 3) 98.2%, 90.3%, 81.1% and 99.1%, respectively. A CECDAI-score of 3 would be a reasonable cut-off value for small bowel CD. Small bowel CD is possible with FC < 100 ug/g. Our results suggest a follow-up with FC before SBCE for patients with no endoscopic ileitis, negative imaging results and FC < 50 ug/g before SBCE.

P166 Predictive markers of Crohn’s disease in small bowel capsule endoscopy

Abstract Background To distinguish between functional gastrointestinal disorders like irritable bowel syndrome (IBS) and Crohn’s disease (CD) can be a burden. The diagnosis is based on symptoms and findings in laboratory tests, endoscopy and imaging. As CD can be limited to small bowel, the diagnosis often requires small bowel capsule endoscopy (SBCE), which is time consuming for both the patient and clinician. Methods To answer this problem, we conducted a retrospective study of 374 patients who underwent SBCE for suspected small bowel CD in Turku University Hospital between 2012 and 2020 and gathered data on the patient’s laboratory, imaging and endoscopic findings at the time of SBCE. The patient’s history, medications and procedures related to CD were also documented after SBCE. SBCE findings were graded along CECDAI (Capsule Endoscopy Crohn’s Disease Activity Index) -scoring system. The main goal was to find predictive markers to rule out clinically significant small bowel CD without proceeding to SBCE. Results Small bowel CD was diagnosed in 110 (29.4%) patients (CD-group). The mean follow-up time for the whole population was 4.4 years. Fecal calprotectin (FC), serum albumin (Alb) and erythrocyte sedimentation rate (ESR) were significantly different between CD and non-CD-groups (p=&amp;lt;0.001, 0.025 and 0.022). Hemoglobin (Hb) and C-reactive protein (CRP) had no significant differences between the two groups (p=0.59, 0.24). FC &amp;lt;50ug/g had sensitivity 96.4%, specificity 19.6%, positive predictive value (PPV) 34.6% and negative predictive value (NPV) 92.5% for small bowel CD. 13 (11.8%) patients in CD-group had FC &amp;lt;100ug/g. CECDAI-score has no previously established clear cut-off-value for the diagnosis of CD. In this study 98.2% of patients in CD-group had CECDAI of 3 or more whereas 90.5% of patients in non-CD-group had CECDAI less than 3 (PPV=81.1%, NPV=99.1%). Sensitivity and specificity were the highest between CECDAI 2.5 and 3.5. Small bowel imaging also had relatively low sensitivity (65.1%) and specificity (72.7%) considering small bowel CD (PPV=52.2%, NPV=81.8%). Conclusion These findings underline our experience, that diagnosis of small bowel CD can be difficult. In this study, we found out that clinically relevant small bowel CD is possible even with FC&amp;lt;100ug/g. Based on our results, we suggest for a follow-up with FC before SBCE for patients with no endoscopic ileitis, negative imaging results and FC &amp;lt;50 ug/g. CECDAI-score of 3 would be a reasonable cut-off value for small bowel CD.

P–606 A second stimulation in the same ovarian cycle rescues advanced-maternal-age patients obtaining ≤ 3 blastocysts after the conventional approach by preventing treatment-discontinuation

Abstract Study question Is double stimulation in the same ovarian cycle (DuoStim) a valuable strategy to rescue advanced-maternal-age patients obtaining ≤ 3 blastocysts for chromosomal-testing after conventional stimulation? Summary answer DuoStim is effective to prevent treatment discontinuation thereby increasing the 1-year cumulative-live-birth-rate among advanced-maternal-age patients obtaining 0–3 blastocysts after a first conventional stimulation. What is known already Folliculogenesis is characterized by continuous waves of follicular growth. DuoStim approach exploits these dynamics to conduct two stimulations in a single ovarian cycle and improve the prognosis of advanced-maternal-age and/or reduced-ovarian-reserve women. Independent groups worldwide successfully adopted DuoStim with various regimens reporting similar oocyte/embryo competence after both stimulations. Recently, we have demonstrated the fruitful adoption of DuoStim in patients fulfilling the Bologna criteria, especially because of the prevention of treatment discontinuation. Here we aimed at investigating whether DuoStim can be adopted to rescue poor prognosis patients obtaining 0–3 blastocysts after the conventional approach. Study design, size, duration Proof-of-concept matched case-control study. All patients obtaining 0–3 blastocysts after conventional-stimulation between 2015–2018 were proposed DuoStim. The 143 couples who accepted were matched for maternal age, sperm factor, cumulus-oocyte-complexes and blastocysts obtained after the first stimulation to 143 couples who did not. The primary outcome was the 1-year cumulative-live-birth-rate. If not delivering, the control group had 1 year to undergo a second attempt with conventional-stimulation. All treatments were concluded (live-birth achieved or no euploid left). Participants/materials, setting, methods Only GnRH-antagonist with recombinant-gonadotrophins and agonist trigger stimulation protocols were adopted. All cycles entailed ICSI with ejaculated sperm, blastocyst culture, trophectoderm biopsy, comprehensive-chromosome-testing and vitrified-warmed euploid single-embryo-transfer(s). Cumulative-live-birth-rate was calculated per patient considering both stimulations in the same ovarian cycle (DuoStim group) or up to two stimulations in 1 year (control group). Treatment discontinuation rate in the control group was calculated as patients who did not return for a second stimulation among non-pregnant ones. Main results and the role of chance Among the 286 couples included (41.0±2.9yr;4.9±3.1 cumulus-oocytes-complexes and 0.8±0.9 blastocysts), 126 (63 per group), 98 (49 per group), 52 (26 per group) and 10 (5 per group) obtained 0,1,2 and 3 blastocysts after the first stimulation, respectively. The cumulative-live-birth-rate was 9% in the control group after the first attempt (N = 13/143). Among the 130 non-pregnant patients, only 12 returned within 1-year (165±95days later;discontinuation rate=118/130,91%), and 3 delivered. Thus, the cumulative-live-birth-rate from two stimulations in 1-year was 11% (N = 16/143). In the DuoStim group, the cumulative-live-birth-rate was 24% (N = 35/143; Fisher’s-exact-test&amp;lt; 0.01,power=80%). The odds-ratio of delivering in the DuoStim versus the control group adjusted for all matching criteria was 3.3,95%CI:1.6–7.0,p&amp;lt;0.01. This difference (0%,22%,15% and 20% in the control versus 10%,31%,46% and 40% in the DuoStim group among patients obtaining 0,1,2 and 3 blastocysts at the first stimulation, respectively) is mainly due to treatment discontinuation in the control group (98%,65%,77% and 80% among patients obtaining 0,1,2 and 3 blastocysts at the first stimulation, respectively) and the further increased maternal age at the time of second retrieval (∼6 months). Notably, 2 patients delivered 2 live-births after DuoStim (none in the control) and 14 patients with a live-birth have euploid blastocysts left (2 in the control). Limitations, reasons for caution Randomized-controlled-trials and cost-effectiveness analyses are desirable to confirm these data. Moreover, 75% of the patients included were &amp;gt;39yr and 44% obtained no blastocyst after the first stimulation. Therefore future studies among younger women and/or more women obtaining ≥1 blastocyst are advisable to set reasonable cut-off values to apply this strategy. Wider implications of the findings: A second stimulation in the same ovarian cycle might be envisioned as a rescue strategy for poor IVF outcomes after a first stimulation, so to prevent treatment discontinuation and increase the cumulative-live-birth-rate. This is feasible since 6–7 days span the first and the second stimulation in the DuoStim protocol. Trial registration number none

Incidence and Risk Factors for Antiplatelet Therapy-Related Bleeding Complications Among Elderly Patients After Coronary Stenting: A Multicenter Retrospective Observation.

Purpose: To determine the incidence and risk factors of bleeding events as well as assess the performance of the PRECISE-DAPT score in elderly patients (≥75 years) who underwent percutaneous coronary intervention (PCI) and one-year dual antiplatelet therapy (DAPT).Methods: A total of 940 patients (≥75 years) who received PCI and one-year DAPT were retrospectively enrolled into the study. The multivariable logistic regression analysis was conducted to identify risk factors of antiplatelet-related bleeding complications. The receiver operating characteristic (ROC) curve analysis and the Delong test were performed to obtain the optimized PRECISE-DAPT score.Results: It was observed that 89 (9.47%) patients suffered bleeding complications, while 37 (3.94%) of them had the Bleeding Academic Research Consortium (BARC, type ≥2) bleeding events. We stratified the PRECISE-DAPT score in tertiles (T1: ≤23; T2:24 to 32; T3: ≥33) and found that BARC ≥ 2 type bleeding occurred more frequently in T3 than in T1 and T2 (8.25 vs. 1.46% vs. 2.40%, p <0.05). The ROC curve analysis revealed that the PRECISE-DAPT score cutoff for BARC ≥2 type bleeding prediction was 33. In comparison with the current recommended cutoff score of 25 (AUC: 0.608, based on ROC analysis), the Delong test indicated significantly improved ability for predicting BARC ≥ 2 type bleeding events using the proposed cutoff value of 33, AUC of 0.676 (p = 0.03), and Brier Score of 0.04. The multivariable logistic regression analysis demonstrated that the PRECISE-DAPT score ≥ 33 [OR: 3.772; 95% CI (1.229, 11.578); p = 0.02] was associated with BARC ≥ 2 type bleeding event, along with a history of hemorrhagic stroke [OR: 6.806; 95% CI (1.465, 31.613); p = 0.014], peptic ulcer [OR: 3.871; 95% CI (1.378, 10.871); p = 0.01], and/or myocardial infarction [MI, OR: 3.081; 95% CI (1.140, 8.326); p = 0.027].Conclusion: A higher PRECISE-DAPT score of 33 might be a more reasonable cutoff value for predicting BARC ≥2 type bleeding risk in CAD patients (≥75 years). In addition, the history of hemorrhagic stroke, peptic ulcer, and myocardial infarction were identified as the risk factors of BARC ≥2 type bleeding events.

53 years old is a reasonable cut-off value to define young and old patients in clear cell renal cell carcinoma: a study based on TCGA and SEER database

BackgroundThe objectives of this study were to screen out cut-off age value and age-related differentially expressed genes (DEGs) in clear cell renal cell carcinoma (CCRCC) from Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database.MethodsWe selected 45,974 CCRCC patients from SEER and 530 RNA-seq data from TCGA database. The age cut-off value was defined using the X-tile program. Propensity score matching (PSM) was used to balance the differences between young and old groups. Hazard ratio (HR) was applied to evaluate prognostic risk of age in different subgroups. Age-related DEGs were identified via RNA-seq data. Survival analysis was used to assess the relationship between DEGs and prognosis.ResultsIn this study, we divided the patients into young (n = 14,276) and old (n = 31,698) subgroups according to cut-off value (age = 53). Age > 53 years was indicated as independent risk factor for overall survival (OS) and cancer specific survival (CSS) of CCRCC before and after PSM. The prognosis of old group was worse than that in young group. Eleven gene were differential expression between the younger and older groups in CCRCC. The expression levels of PLA2G2A and SIX2 were related to prognosis of the elderly.ConclusionFifty-three years old was cut-off value in CCRCC. The prognosis of the elderly was worse than young people. It remind clinicians that more attention and better treatment should be given to CCRCC patients who are over 53 years old. PLA2G2A and SIX2 were age-related differential genes which might play an important role in the poor prognosis of elderly CCRCC patients.

A method for estimating the transmissibility of influenza using serial cross-sectional seroepidemiological data

BackgroundSeroepidemiological surveillance data has been demonstrated to be useful for estimating the cumulative incidence of influenza, and measures the difference between pre- and post-epidemic seropositive fractions. Despite this, such studies relied on a chosen cut-off value for seropositivity. The aim of the present study is to develop a method to analyze distributions of serial cross-sectional seroepidemiological surveillance datasets using an epidemiological model so that the transmission potential can be estimated without imposing a cut-off value. MethodsA mathematical model of influenza transmission with a discrete antibody titer level was constructed. The final size equation for pre- and post-epidemic titer levels was derived. Subsequently, using the estimated distribution of the dilution increase caused by infection and the measurement error distribution, the model parameters were optimized using the maximum likelihood method. A bootstrap-based confidence interval calculation and sensitivity analysis were also performed. ResultsWithout imposing a cut-off value, the cumulative incidence was quantified, thereby yielding an estimate of the basic reproduction number. For the purpose of exposition, the proposed method was applied to influenza A/Victoria/3/75(H3N2) data, and serological data between 1975 and 1976 were compared. The estimated reproduction number was greater than that using the cut-off value of the hemagglutination inhibition level with titer level 20 (dilution 1:20) or above to define positives. ConclusionThe proposed method without a cut-off value offers an unbiased approach to estimating the cumulative incidence along with the reproduction number. If a cut-off value is required, the results imply that titer level 20 or above may better represent a reasonable cut-off value for calculating the incidence, but it could underestimate the basic reproduction number.

Young Age Breast Cancer: Profiles and Overall Survival in Dr. Soetomo Oncology Center, Surabaya, Indonesia

Background: Breast cancer still become the most common cancer affecting women worldwide with 2 million new cases diagnosed each year and it is also the leading cause of death from cancer among women including Asia. According to SEER program database, the vast majority of women diagnosed after the age of 40 years and only around 7% are in the age group under 40 years. Recently, breast cancer arising in young women gaining more interest due to its aggressive behavior and unfavorable prognosis compared to the older patients. In addition, the lack of knowledge and awareness of the disease, absence of effective breast cancer screening tool for women under 40 are thought to contribute its advanced presentation at diagnosis. This certainly affects the outcome and overall survival (OS) of this age group. Despite discrepancies in adverse prognostic features, younger age has been shown in several studies to be an independent predictor of adverse outcome. To date, no consensus has been reached about the definitions of “young age” and “very young age” breast cancer. Nevertheless, several studies support that, 40 years is a reasonable cutoff value for defining “young”. Various efforts have been made to better understand the nature of young age breast cancer (YABC) which apparently represents a distinct entity with a unique underlying biology. However,because breast cancer occurs at a much lower rate among young women than in our older counterparts, they remain underrepresented in many research studies. The aim of this study was to identify the profile and overall survival in the group of YABC patients referred to Oncology Center at Dr. Soetomo Hospital, Surabaya, Indonesia.

Surgical Offloading Techniques Should be Used More Often and Earlier in Treating Forefoot Diabetic Ulcers: An Evidence-Based Review.

Conservative treatment is the basis for diabetic foot ulcer (DFU) management, whereas surgical treatment is usually reserved for patients with failed, recurrent, or nonresponsive infected wounds. However, many reports demonstrated good to excellent results following surgery. Evidence synthesis on surgical offloading techniques and clear guidelines regarding the timing of surgery are lacking. The present study aimed to investigate the evidence behind surgical offloading techniques and propose a cutoff time for surgical indication following failed conservative treatment of neuropathic diabetic forefoot ulcers. Electronic databases were searched from inception to identify the best evidence level articles related to non-vascular surgical treatment of DFUs, such as metatarsal head resection, resection arthroplasty, metatarsal osteotomy, Achilles tendon lengthening, gastrocnemius recession, and flexor tenotomy, that have been employed for managing DFUs. Based on the highest level of evidence available, surgery was found to generate better values than standard conservative care for all outcomes except for the transfer rate. In particular, surgical bony offloading procedures demonstrated significantly better outcomes than standard conservative nonsurgical care in terms of higher healing rates, shorter healing durations, and lower recurrence rates. Moreover, 96% of DFUs healed in <1 month following surgical bony offloading, whereas 68% of ulcers healed within 3 months after standard care. The findings could challenge the classical guidelines of DFU management. This evidence-based review indicates that surgical offloading could be used more often and be proposed earlier during the course of ulcer management. The results imply that a period of 12 weeks could be considered a reasonable cutoff value to consider surgical treatment for patients with nonhealing DFUs.

Determination of Clinical Cut-Off Values for Serum Cystatin C Levels to Predict Ischemic Stroke Risk

Background: The association between cystatin C and risk of ischemic stroke is inconsistent and the cut-off values of cystatin C are diverse in different articles. We aimed to investigate the association between cystatin C levels and the development of ischemic stroke and to explore the clinical cut-off values of serum cystatin C levels for ischemic stroke. Methods: This prospective cohort study included 7658 participants from the China Health and Retirement Longitudinal Study who were free of cardiovascular diseases and cancer at baseline. A decision-tree model was used to find reasonable cut-off values for cystatin C levels. Logistic regression models were used to analyze the association between different levels of cystatin C and the risk of ischemic stroke. Results: The whole cohort was divided into the following 3 groups according to the decision tree: group-low (<.901 mg/L), group-moderate (.901∼1.235 mg/L), and group-high (>1.235 mg/L). After 4 years of follow-up, we identified 156 cases of ischemic stroke. After adjusting for potential confounding factors, the odds ratios (95% confidence intervals) of ischemic stroke were 1.637 (1.048-2.556) for group-moderate and 2.326 (1.285-4.210) for group-high) compared with the low group of cystatin C. Subgroup analyses showed that the association between cystatin C levels and the incidence of ischemic stroke was more pronounced in males or old people than in females or young people. Conclusions: We found 2 suitable cut-off values for serum cystatin C levels and found that high levels of cystatin C were associated with an increased risk of ischemic stroke.

Interpretation of hair analysis for fentanyl and analogues

Nowadays, the detection of new psychoactive substances (NPS) in hair has been extensively described. Although most NPS fall into the classes of synthetic cannabinoids and designer cathinones, novel synthetic opioids (NSO) have also appeared recently on the drug market with a progressive increase in their consumption. In turn, also the detection of NSO in hair has already been presented [1] , but their results interpretation still presents several controversial issues, as is quite common in hair analysis. Lack of knowledge about both effective dosage of NSO and their keratin binding make any attempt to establish a reasonable cut-off value for each drug questionable. In this presentation, preliminary results from a large dataset of real samples positive to fentanyl or analogues will be discussed. A simple, fast, specific and sensitive UHPLC-MS/MS method able to detect 13 synthetic opioids (including fentanyl analogues) and metabolites in 25 mg of hair was applied to 293 real samples. LOD values were in the range 0.1–0.3 pg/mg for all analytes, with the exception of oxycodone which was 1.5 pg/mg. Samples were collected in the United States between November 2016 and August 2018 from subjects who had reported heroin use in the last year or had already tested positive to common opiates. The range of concentrations, mean and median were calculated for each analyte. In particular, 68% of samples resulted positive for fentanyl at concentrations between LOQ and 8600 pg/mg. The mean value was 382 pg/mg and the median was 95 pg/mg. Furthermore, the metabolites norfentanyl and 4-ANPP were also monitored. Ranges of values lied between LOQ and 320 pg/mg and between 1 and 1400 pg/mg, respectively. The ratio norfentanyl/fentanyl, 4-ANPP/fentanyl and norfentanyl/4-ANPP were also evaluated. Fentanyl and analogues were measured in a wide range of concentrations. Median and box-plot calculations were used to draw a preliminary direction for a possible cut-off to discriminate between exposure to either low or high quantities of the drug. The main metabolites could also be detected in the majority of hair samples, thus the active use could be confirmed. Finally, several ratios proved promising as possible markers of active use and to discriminate the intake of fentanyl from other analogues. Like other classes of NPS, more data about the detection of NSO in hair are needed before any clear interpretation of analytical findings can be given. However, our preliminary results provide a useful starting point for a wide discussion aimed to a better understanding of fentanyl (and analogues) positive testing from hair analysis.

Developing and Validating an Age-Independent Equation Using Multi-Frequency Bioelectrical Impedance Analysis for Estimation of Appendicular Skeletal Muscle Mass and Establishing a Cutoff for Sarcopenia.

Background: Appendicular skeletal muscle (or lean) mass (ALM) estimated using dual-energy X-ray absorptiometry (DXA) is considered to be a preferred method for sarcopenia studies. However, DXA is expensive, has limited portability, and requires radiation exposure. Bioelectrical impedance analysis (BIA) is inexpensive, easy to use, and portable; thus BIA might be useful in sarcopenia investigations. However, a large variety of models have been commercially supplied by different companies, and for most consumer products, the equations estimating ALM are not disclosed. It is therefore difficult to use these equations for research purposes. In particular, the BIA equation is often age-dependent, which leads to fundamental difficulty in examining age-related ALM loss. The aims of the current study were as follows: (1) to develop and validate an equation to estimate ALM using multi-frequency BIA (MF-BIA) based on theoretical models, and (2) to establish sarcopenia cutoff values using the equation for the Japanese population. Methods: We measured height (Ht), weight, and ALM obtained using DXA and a standing-posture 8-electrode MF-BIA (5, 50, 250 kHz) in 756 Japanese individuals aged 18 to 86-years-old (222 men and 301 women as developing equation group and 97 men and 136 women as a cross validation group). The traditional impedance index (Ht2/Z50) and impedance ratio of high and low frequency (Z250/Z5) of hand to foot values were calculated. Multiple regression analyses were conducted with ALM as dependent variable in men and women separately. Results: We created the following equations: ALM = (0.6947 × (Ht2/Z50)) + (−55.24 × (Z250/Z5)) + (−10,940 × (1/Z50)) + 51.33 for men, and ALM = (0.6144 × (Ht2/Z50)) + (−36.61 × (Z250/Z5)) + (−9332 × (1/Z50)) + 37.91 for women. Additionally, we conducted measurements in 1624 men and 1368 women aged 18 to 40 years to establish sarcopenia cutoff values in the Japanese population. The mean values minus 2 standard deviations of the skeletal muscle mass index (ALM/Ht2) in these participants were 6.8 and 5.7 kg/m2 in men and women, respectively. Conclusion: The current study established and validated a theoretical and age-independent equation using MF-BIA to estimate ALM and provided reasonable sarcopenia cutoff values.

How Young Is Too Young in Breast Cancer?—Young Breast Cancer Is Not a Unique Biological Subtype

BackgroundThere is no uniformly adopted cutoff value to define “young patients” with breast cancer. This study was designed to determine an optimal cutoff value, to investigate prognostic factors and to explore gene expression profiles of young female breast cancer. Materials and MethodsThe Surveillance, Epidemiology, and End Results database was examined to identify cases of female breast cancer diagnosed between 2000 and 2007. The optimal cutoff value for young age was determined using the X-tile program (Yale University, version 3.6.1). Age-specific gene expression profiles were explored using RNA sequence data from the Cancer Genome Atlas database. ResultsThe age of 40 years was determined as the optimal cutoff value. Among 94,087 patients, 12,755 were aged 40 years or younger (younger group), and 81,332 were older (older group). The 5- and 10-year cancer-specific survival rates in younger and older groups were 88.74% and 80.65%, respectively, and 93.22% and 88.43%, respectively (P < .001). Univariate and multivariate analyses indicated younger patients had worse prognosis. Subgroup analysis according to estrogen receptor (ER) showed the risk for cancer-specific death of ER-positive (ER+) younger patients increased by approximately 2 times (hazard ratio, 1.96) compared with ER+ older patients. We failed to find any age-related gene in 509 patients after adjusting according to subtype (50-gene prediction analysis of a microarray) and histological type. ConclusionThe age of 40 years is a reasonable cutoff value for defining “young.” Young patients with breast cancer, especially those in the ER+ subgroup, have worse prognosis. However, we found that young breast cancer is not a unique biological entity, and therefore, a lack of new potential targets.

Usefulness of a novel method for the screening of deep vein thrombosis by using a combined D-dimer- and age-based index before total hip arthroplasty.

Plasma D-dimer level is clinically useful for diagnosing patients with suspected deep vein thrombosis (DVT). However, the cut-off value for the D-dimer level remains controversial and undetermined with regard to total hip arthroplasty (THA). The objective of this study was to estimate the efficacy of an age- and D-dimer-based index for diagnosing DVTs in asymptomatic cases before THA. We enrolled 224 patients with no symptoms associated with DVT before THA. All the patients underwent ultrasonography, and the plasma D-dimer level was recorded about 1 month preoperatively. The optimal cut-off value was calculated using multiple logistic regression and receiver operating curve analyses. DVTs were detected in 13 patients (5.8%) using ultrasonography. Multiple logistic regression analysis demonstrated that age (odds ratio [OR]: 1.13; p = 0.007) and D-dimer value (OR: 1.74; p = 0.003) were related to the existence of preoperative DVT. A DVT index (0.12 × age + 0.45 × the D-dimer value) of 8.15 was the most reasonable cut-off value according to the receiver operating curve analysis. This value caused 100% sensitivity and 70.1% specificity, with an area under the curve (AUC) of 0.905 (range, 0.836–0.975). For age and D-dimer value, the AUCs were 0.828 (0.749–0.907) and 0.716 (0.522–0.910), respectively. This study demonstrated that age and D-dimer index can be useful in screening patients for DVTs before THA. This DVT index is also easy to calculate and may be clinically significant.