Normal Cut-off Value Research Articles

Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II HCC undergoing surgery? An observational cohort study.

The influence of deranged body composition on stage I/II HCC after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed. From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis. A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cutoff values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid β-oxidation was enhanced in with low PMI or high SAT index. The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcome after surgery. Further studies are warranted to validate our findings.

Insulin Resistance-Related Cardiometabolic Risk Among Nondiabetic Childbearing Age Females.

Background: This study evaluates insulin resistance prevalence in young females without diabetes, assessing risk factors and adiposity indices for early detection of cardiometabolic disorders. Methods: A cross-sectional study was conducted, involving 282 females aged 18-35 years from suburban and rural areas of Sri Lanka. Anthropometric measurements [height, weight, waist circumference (WC)] were obtained and biochemical parameters [fasting glucose, insulin, insulin resistance (IR), total cholesterol, high-density lipoproteins, (HDL), low-density lipoproteins, triglycerides] were measured. The anthropometric and biochemical data were compared between the groups of normal weight controls and overweight/obese cases, as well as between females with or without IR. Results: The prevalence of IR in controls and cases were 48.6% and 57.1%, respectively. Both groups had mean Homeostasis Model Assessment-IR values greater than the normal cutoff value of 2.5. Females with IR showed higher prevalence of dyslipidemia than those without IR. Compared to the controls (2.81%), the prevalence of metabolic syndrome (MetS) was substantially greater among cases (46.42%). Both groups showed a statistically significant association between IR and MetS, but the association was considerably stronger in cases [r = 0.616, odds ratio (OR) >8] than in controls (r = 0.175, OR >1). Controls exhibited lower HDL levels, hypertriglyceridemia, and elevated IR levels (P < 0.05), and their ORs for acquiring MetS were >2, <1, and >3, respectively. Importantly, overweight/obese cases exhibited a significant association (P < 0.05) with all the MetS risk variables. Visceral adiposity index (VAI) proves to be a precise measurement for identifying IR and cardiovascular disease (CVD) among young females (Z = -3.651), surpassing the accuracy of other indices. Body mass index, body round index, a body shape index, and WC were also reliable measurements to assess IR and the risk of CVD (P < 0.05). Conclusion: The study underscores the importance of assessing IR in nondiabetic young females to identify early cardiometabolic risks. VAI emerges as a precise measurement for identifying IR and CVD risk, surpassing the accuracy of other indices.

Evaluation of Peripheral Blood Inflammatory Markers in Patients with Chronic Subdural Hematoma.

Chronic subdural hematoma (CSH) refers to intracranial hemorrhages frequently caused by minor head trauma and is mostly seen in middle and advanced age. One of the hypotheses regarding the development of CSH is that the inflammatory cascade plays a pivotal role in this process. The inclusion criteria covered patients in all ages who were diagnosed as CSH by computed tomography and/or magnetic resonance imaging and treated by surgical intervention in our clinic between 2018 and 2020. Patient files were reviewed retrospectively, and medical records of age, gender, trauma history, unilateral or bilateral lesion, and leukocyte, neutrophil, lymphocyte, monocytes, and platelet counts were obtained. Receiver operating characteristic (ROC) analysis was used for the most appropriate neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and age discrimination in the presence of CSH, and multiple logistic regression analyses were used to determine the effect of independent factors on dependent variables. A total of 68 cases, 57 (83.8%) male and 11 (16.2%) female, aged between 13 and 93, were included in the study. The mean age of the patients included in the study was 72.59 ± 13.13 years. NLR of the cases ranged from 1.37 to 34.18, with a mean of 6.53 ± 6.74 and a median of 3.57. NLR and PLR were found to be statistically significantly higher in CSH patients compared to the healthy control group, and the cut-off values for NLR, PLR, and age were 2.8, 132, and 55, respectively. Age and NLR were found to be independent factors associated with CSH (P < 0.05). As seen from the results of this study, peripheral blood values in CSH patients may be significantly higher than in the healthy control group, while they are below the normal laboratory cut-off values.

Methylated ctDNA Quantification: Noninvasive Approach to Monitoring Hepatocellular Carcinoma Burden.

Noninvasive, precision monitoring of hepatocellular carcinoma (HCC) treatment efficacy would greatly facilitate personalized therapy and improve patient outcomes. We hypothesize that quantifying methylated circulating tumor DNA (ctDNA) can be used to effectively monitor HCC burden without the need for biopsy. Blood samples were collected from 25 patients, 21 with HCC and 4 with benign liver masses, at various timepoints throughout the course of treatment at a high-volume academic medical center. Quantification of methylated ctDNA molecules assessed CpG sites on more than 550 preselected cancer-specific amplicons. The tumor methylation score (TMS) was calculated by measuring the difference between the amount of methylation in the plasma and buffy coat with a normal cutoff value of 120 or less. Among 10 patients with surgical HCC (5 surgical resections and 5 liver transplants), TMS revealed a statistically significant, rapid postoperative decline in 9. One patient who had a persistently elevated TMS on postoperative day 1 was subsequently found to have had metastatic disease. Patients in the negative control cohort all had normal-range pre- and postoperative TMS. Preoperative TMS correlated moderately with tumor burden on pathology (Spearman r = 0.54) of surgical specimens. From 11 subjects undergoing systemic therapy or Y90 radioembolization, analysis of 16 time periods demonstrated that the change in TMS (ΔTMS) was better associated with tumor progression than the change in Δalpha-fetoprotein (area under the curve 0.800 and 0.783, respectively). A composite score combining ΔTMS and Δalpha-fetoprotein further improved performance for detecting tumor progression with an area under the curve of 0.892. These findings indicate that ctDNA methylation scores can effectively evaluate changes in tumor burden without the need for tumor biopsy.

Integration of T-cell clonality screening using TRBC-1 in lymphoma suspect samples by flow cytometry.

The diagnosis of T-cell non-Hodgkin lymphomas (NHL) is challenging. The development of a monoclonal antibody specific for T-cell receptor β constant region 1 (TRBC1) provides an alternative to discriminate clonal T cells. The aim of this study was to evaluate the diagnostic potential of an anti-TRBC1 mAb for the identification of T-NHL. We performed a cross-sectional diagnostic analytic study of samples tested for lymphoma. All samples sent for lymphoma screening were first evaluated using the standard Euroflow LST, to which a second additional custom-designed T-cell clonality assessment tube was added CD45/TRBC1/CD2/CD7/CD4/TCRγδ/CD3. Flow cytometry reports were compared with morphological and molecular tests. Fifty-nine patient samples were evaluated. Within the T-cell population, cut-off percentages in the CD4+ cells were from 29.4 to 54.6% and from 23.9 to 52.1% in CD8+ cells. Cut-off ratios in CD4+ T cells were from 0.33 to 1.1, and in CD8+ cells between 0.22 and 1.0. Using predefined normal cut-off values, 18 of 59 (30.5%) samples showed a restricted expression of TRBC1. A final diagnosis of a T-NHL was confirmed clinically and/or by histopathological studies in 15 of the 18 cases (83.3%). There were no cases of T-NHL by morphology/IHC with normal TRBC1 expression. Non-neoplastic patient samples behaved between predefined TRBC1 cut-off values. Expression of TRBC1 provides a robust method for T-cell clonality assessment, with very high sensitivity and good correlation with complementary methods. TRBC1 can be integrated into routine lymphoma screening strategies via flow cytometry.

Expiratory Diameter of the Inferior Vena Cava Diameter IVC Across Age Groups in CCF Subjects

Background: Dilatation of the Inferior Vena Cava (IVC) is used as the ultrasonic diagnostic feature in patients suspected of congestive heart failure. The IVC diameter has being reported to vary among the various age ranges. Knowledge of these variations is useful in precision diagnoses of CHF by imaging scientists. Aim: The study aimed to determining the ultrasonic mean expiratory diameter of the IVC across the various age ranges with CCF in Azare, Bauchi State-Nigeria. Methods: One hundred and ninety-nine subjects of both sexes diagnosed with Congestive Cardiac Failure were randomly grouped into six age groups. A structured questionnaire was used to rule out those that fell within the exclusion criteria. Their informed consent was sought for abdominal ultrasound scan. The probe was placed on the mid line of the body, half-way between the xiphoid process and the umbilicus with the marker on the probe directed towards the patient`s head to obtain a longitudinal view of the IVC. The maximum IVC diameter was measured from the subcostal view using the electronic caliper of the scan machine during expiration on a B mode. The mean value of each group was obtained and analyzed statistically. Results: It was observed that, the mean expiratory diameter of the IVC across the age group (18-27, 28-37, 38-47, 48-57, 58-67 and 68-77) years were (1.89, 1.96, 1.94, 2.06, 1.91, 1.97 and 1.94) cm, respectively P-value ≤ 0.05. Conclusion: In conclusion, the normal cutoff values for indicating a dilated IVC across the different age strata in the populace has been established.

Evaluation of blood pressure response during dobutamine stress echocardiography in patients without cardiovascular diseases.

Dobutamine stress echocardiography (DSE) is a diagnostic tool for determining coronary artery disease. Considering hypotension and hypertension as important complications of DSE, we aimed to evaluate the blood pressure (BP) responses during DSE. Patients without known cardiovascular diseases who underwent DSE were included. We excluded patients who had hypertension, diabetes mellitus, a known history of cardiovascular diseases, and those taking vasoactive medications. Systolic (SBP) and diastolic (DBP) blood pressure were recorded at baseline and peak stress. We included 688 patients with an age of 57.9 ± 12.01 years. During DSE, SBP (+19.72 ± 26.51 mm Hg, p < 0.001), DBP (+5.52 ± 17.35 mm Hg, p < 0.001), and HR (+54.05 ± 22.45 bpm, p < 0.001) significantly increased from baseline to peak stress. The normal cut-off value was measured between 101-210 mm Hg for SBP and 50-121 mm Hg for DBP. According to this normal cutoff, 11 (1.3%) and 30 (4.4%) patients had hypotensive and hypertensive SBP and 15 (2.2%) and 21 (3.1%) patients had hypotensive and hypertensive DBP, respectively. The hypotensive response was correlated with baseline SBP (r = 0.6, p = 0.001) and atropine (r = -2.18, p = 0.043), and the hypertensive response was correlated with baseline SBP (r = 0.048, p < 0.001). Baseline BP and atropine consumption were the independent variables associated with the outside-the-normal range of blood pressure responses.

INTEGRATION OF T‐CELL CLONALITY SCREENING USING TRBC‐1 IN LYMPHOMA SUSPECT SAMPLES BY FLOW CYTOMETRY

Background: The diagnosis of T-cell non-Hodgkin lymphomas (NHL) is challenging. Many cases of T-NHL have normal immunophenotypes, and currently available T-cell clonality assays have limitations, including suboptimal sensitivity. The development of a monoclonal antibody (mAb) specific for T-cell receptor β constant region 1 (TRBC1) provides an alternative to discriminate clonal T cells. The aim of this study was to evaluate the diagnostic potential of an anti-TRBC1 mAb for the identification of T-NHL. Materials and Methods: We performed a cross-sectional diagnostic analytic study of samples tested for lymphoma. All samples sent for lymphoma screening were first evaluated using the standard Euroflow Lymphoma Screening Tube (LST), to which a second additional custom-designed T-cell clonality assessment tube was added. LST tube included CD45/CD3/CD4/CD5/CD8/CD19/ CD20/CD38/TRCγδ/CD56 and the second CD45/TRBC1/CD2/CD7/CD4/TRCγδ/CD3. The results of TRBC1 expression in patient samples were compared to the normal expression of TRBC1 in 10 normal samples of peripheral blood (PB). Flow cytometry reports were compared with morphological and molecular tests. Clinical data were obtained from the electronic database. This study was approved by the institutional IRB and Clinical Ethics Committee. Results: 69 samples were evaluated. 10 healthy controls, and 59 patient samples. Overall, individuals had a median of 52 years (interquartile range [IRQ], 35–70 years) and 53.6% were female. Normal TRBC1 expression was assessed in 10 normal PB samples. Within the T-cell population (CD45+/CD3+), CD4+ cells expressed (±SD) TRBC1 in 42% (4.2), while CD8+ cells in 38% (4.7). This resulted in a TRBC1+/- ratio of 0.72 ± 0.13 for CD4+ and 0.61 ± 0.13 for CD8+ T cells. Cut-off percentages in the CD4+ cells were from 29.4% to 54.6%, and from 23.9 to 52.1% in CD8+ T-cells. Cut-off ratios in CD4+ T cells were from 0.33 to 1.1, and in CD8+ T cells between 0.22 and 1.0. Using predefined normal cut-off values, 18 of 59 (30.5%) samples showed a restricted (monotypic) expression of TRBC1. 6/18 were monotypic positive (33.3%) and 12/18 were monotypic negative (66.6%). A final diagnosis of a T-NHL was confirmed by IHC in 15 of the 18 cases (83.3%). A molecular TCR gene rearrangement assay was available in 3/15 cases, which confirmed clonality. The 3 discordant cases were 2 samples from an EBV+ primary effusion lymphoma (PEL) and 1 of lung adenocarcinoma. There were no cases of a diagnosis of a T-NHL by morphology / IHC with normal TRBC1 expression. Non-neoplastic patient samples behaved between predefined TRBC1 cut-off values. Conclusions: Expression of TRBC1 provides a robust method for T- cell clonality assessment, with very high sensitivity and good correlation with complementary methods. TRBC1 can be integrated into routine lymphoma screening strategies via flow cytometry to improve T-NHL diagnosis capacities. The research was funded by: Fondecyt 11200805 Clínica Alemana de Santiago ID1025 Keyword: diagnostic and prognostic biomarkers No conflicts of interests pertinent to the abstract.

Diagnostic strategies in adrenal insufficiency.

Adrenal insufficiency (AI) is the clinical manifestation of deficient production of glucocorticoids with occasionally deficiency also in mineralocorticoids and adrenal androgens and constitutes a fatal disorder if left untreated. The aim of this review is to summarize the new trends in diagnostic methods used for determining the presence of AI. Novel aetiologies of AI have emerged; severe acute respiratory syndrome coronavirus 2 infection was linked to increased frequency of primary AI (PAI). A new class of drugs, the immune checkpoint inhibitors (ICIs) widely used for the treatment of several malignancies, has been implicated mostly with secondary AI, but also with PAI. Salivary cortisol is considered a noninvasive and patient-friendly tool and has shown promising results in diagnosing AI, although the normal cut-off values remain an issue of debate depending on the technique used. Liquid chromatography-mass spectrometry (LC-MS/MS) is the most reliable technique although not widely available. Our research has shown that little progress has been made regarding our knowledge on AI. Coronavirus disease 2019 and ICIs use constitute new evidence on the pathogenesis of AI. The short synacthen test (SST) remains the 'gold-standard' method for confirmation of AI diagnosis, although salivary cortisol is a promising tool.

Diagnostic performance of traditional radiographic indices in detection of carpal collapse in Kienböck's disease.

Correctly identifying carpal collapse is important for adequate treatment of Kienböck's disease. This study aimed to assess the accuracy of traditional radiographic indices in detecting carpal collapse to differentiate between Lichtman stages IIIa and IIIb. In 301 patients, carpal height ratio, revised carpal height ratio, Ståhl index and radioscaphoid angle were measured on plain radiographs by two blinded observers. As a reference standard, Lichtman stages were determined by an expert radiologist using CT and MR imaging. The interobserver agreement was excellent. In the differentiation between Lichtman stages IIIa and IIIb, measurements of indices showed moderate to good sensitivity (0.60-0.95) and low specificity (0.09-0.69) using normal cut-off values from the literature, while receiver operating curve analysis revealed poor area under the curve (58-66%). Traditional radiographic indices showed poor diagnostic performance in detecting carpal collapse in Kienböck's disease and did not reach sufficient accuracy in the differentiation between Lichtman stages IIIa and IIIb.Level of evidence: III.

Ultrasonography in the assessment of disease activity in cranial and large-vessel giant cell arteritis: a prospective follow-up study.

We evaluated sensitivity to change and discriminative abilities of vascular US scores in disease monitoring in the follow-up of a prospective cohort of new-onset cranial and large-vessel (LV) GCA patients. Baseline and follow-up (8 weeks, 24 weeks and 15 months) US of temporal arteries (TA), carotid and axillary arteries (LV) included assessment of halo and measurement of the intima media complex (IMC). Max IMC, max halo IMC, sum IMC, sum halo IMC, mean IMC, halo count and the Southend halo score were calculated. The provisional OMERACT US score, OGUS, was obtained, taking the average of temporal arteries and axillary arteries IMCs divided by their normal cut-off values. Baseline US was positive in 44/47 patients (72% TA, 72% LV). Sensitivity to change of all composite US scores containing TAs was evident by week 8 onward. LVs responded poorly and new axillary US lesions emerged in six patients despite clinical remission. The OGUS showed a large magnitude of change and is considered the score least prone to potential bias. All TA-based US scores showed moderate-strong correlation with disease activity markers. OGUS, TA halo count, Southend TA halo score, TA sum IMC and TA mean IMC showed potential to discriminate remission and relapse with area under the curve ≥0.8. The OGUS is suggested as an outcome measurement for the assessment of treatment response in clinical trials. The abilities of US scores to discriminate remission and relapse are encouraging and should be further explored.

Utility of Combining High-Sensitive Cardiac Troponin I and PESI Score for Risk Management in Patients with Pulmonary Embolism in the Emergency Department.

Pulmonary embolism (PE) has a major burden of morbidity and mortality, consequently the need for a prompt risk stratification for these subjects is crucial. In order to evaluate the risk management and final disposition of patients with PE in the Emergency Department (ED), we conducted a study that was divided in two phases: Phase I retrospective study (RS), Phase II prospective study (PS). In Phase I, 291 patients were enrolled while in Phase II, 83 subjects were evaluated. In both study phases, the enrolled subjects were analyzed for final disposition in ED using PESI score, right ventricle (RV) imaging, and high-sensitive cardiac troponin I (hs-cTnI) data. The RS patients were divided into low risk and high risk according to the sPESI score, while PS patients were grouped in low, intermediate, and high risk classes according to PESI score. In both study phases, all the studied patients were further divided into negative (hs-cTnI-) or positive (hs-cTnI+) groups according to hs-cTnI levels within normal or above cutoff values, respectively. For all enrolled subjects, CT pulmonary angiography was analyzed to assess the RV/LV diameter and volume ratio as an indicator of RV involvement. In both RS and PS phases, hs-cTnI+ group showed a higher PESI score. Nevertheless, a significant percentage of hs-cTnI+ patients resulted to be in the low-risk PESI class. Patients with a positive RV/LV ratio were more likely to have a hs-cTnI+ (p < 0.01), while among those with a negative ratio, 24 to 32% showed as hs-cTnI+. In the hs-cTnI+ group from both study phases, patients were more likely to be admitted in an ICU (RR 3.7, IC: 2.1-6.5). In conclusion, in patients with PE in the ED compared PESI score alone, the combination of hs-cTnI and PESI seems to be of greater utility in improving risk stratification and final disposition decision-making.

Posterior femoral cutaneous nerve sensory conduction study in a sample of apparently healthy Egyptian volunteers

BackgroundPosterior femoral cutaneous nerve (posterior cutaneous nerve of the thigh) is a sensory nerve arises from the sacral plexus. Its terminal part supplies the skin of the posterior surface of the thigh and popliteal fossa, and it extends for a variable length below the popliteal fossa till the mid-calf region. The aim was to assess the posterior femoral cutaneous nerve antidromic sensory conduction technique and estimate its different sensory nerve action potential parameters’ reference values in a sample of apparently healthy Egyptian participants. One hundred and twenty lower limbs of 60 apparently healthy Egyptian volunteers were included. Clinical evaluation and sensory conduction study for the posterior femoral cutaneous nerve were done.ResultsPosterior femoral cutaneous nerve sensory nerve action potential was elicited in 98 lower limbs (81.6%) of 52 individuals (86.7%). The obtained results of different parameters of posterior femoral cutaneous nerve sensory nerve action potential were as the following: onset latency (2.04 ± 0.21 ms), peak latency (2.86 ± 0.25 ms), conduction velocity (59.45 ± 6.36 m/s) and amplitude (6.16 ± 2.29 μV). No significant differences between the two genders were found regarding different parameters of posterior femoral cutaneous nerve sensory nerve action potential except for amplitude which was significantly larger among male participants (P = 0.030). No significant differences between the right and left lower limbs were found regarding different parameters of sensory nerve action potential. There was a statistical significant negative correlation between age and posterior femoral cutaneous nerve conduction velocity (P = 0.008). There was a statistical significant positive correlation between height and peak latency (P ≤ 0.0001), as well as, a statistical significant negative correlation between height and conduction velocity (P ≤ 0.0001). There was a statistical significant negative correlation between body mass index and posterior femoral cutaneous nerve peak latency (P = 0.008).ConclusionsThe research provides a reliable electrophysiological antidromic sensory conduction study for the posterior femoral cutaneous nerve and normal cut-off reference values for posterior femoral cutaneous nerve sensory nerve action potential parameters. This is essential for the evaluation of suspected posterior femoral cutaneous nerve lesions.

Comparison of the red blood cell indices based on accuracy, sensitivity, and specificity to predict one-year mortality in heart failure patients

BackgroundVarious investigations have specified the role of each RBC indices separately [including hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW)] to predict the prognosis of acute heart failure (AHF) patients. However, in the current study, these variables were compared based on accuracy, sensitivity, and specificity to determine the best prognostic factor.MethodsOf 734 heart failure patients referred to the emergency department, 400 cases were enrolled based on the inclusion and exclusion criteria. Data of them were documented, and patients were followed for one year. Eventually, the association of clinical variables and RBC indices with one-year mortality was explored.ResultsThe study included 226 (56%) men and 174 (44%) women with a median age of 66 years. Body Mass Index (HR 1.098, p = 0.016), Hb (HR 0.728, p = 0.024), HTC (HR 0.875, p = 0.066), MCHC (HR 0.795, p = 0.037), and RDW-CV (HR 1.174, p = 0.006) were confirmed as predictors of long-term mortality. Despite confirming the predictive role of these variables by ROC curves, their sensitivity and specificity were reported as follows: [72% and 50% for Hb], [75% and 52% for HCT], [88% and 27% for MCHC], and [49% and 81% for RDW]. In addition, stratified groups of patients, based on normal cut-off values obtained from scientific literature, had significantly different survival in Kaplan–Meier analyses.ConclusionWhilst proving the predictive role of Hb, HCT, MCHC, and RDW in AHF patients, the most sensitive measurement was MCHC and the most specific one was RDW; therefore, these variables should be considered for risk stratification purposes of AHF patients in daily clinical practice.

Diagnostic Tests for Hypofibrinogenemia Resulting from Green Pit Viper (Trimeresurus albolabris) Envenomation: A Simulated In Vitro Study.

The green pit viper (GPV) Trimeresurus albolabris is found in Southeast Asia. Its venom has a thrombin-like activity that can cause hypofibrinogenemia. Fibrinogen measurement is not always available. We aimed to establish a more available diagnostic tool indicating hypofibrinogenemia caused by GPV envenomation. This was an in vitro study, in which healthy subjects aged 20 to 45 y were enrolled. There were 2 experiments. In Experiment 1, blood samples from 1 subject had varying amounts of T albolabris venom added to determine its effect on the fibrinogen level (FL). In Experiment 2, 3 sets of blood samples were obtained from another 25 subjects. The 2 venom doses established in Experiment 1 were used on 2 sets of the samples to simulate severe (FL <1.0 g·L-1) and mild hypofibrinogenemia (FL 1.0-1.7 g·L-1). The third set of samples was venom-free. All samples were used for platelet counts, prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT), and 2 bedside clotting tests. Diagnostic parameters were calculated against the target FL of <1.0 g·L-1 and <1.7 g·L-1. Twenty-five subjects were enrolled in Experiment 2. On referencing normal cutoff values (platelet count >150,000 cells/mm3, venous clotting time <15 min, normal 20-min whole blood clotting time, INR <1.2, aPTT <30), we found abnormalities of 5, 0, 0, 3, and 22%, respectively. The highest correlation with hypofibrinogenemia was provided by PT/INR. For an FL of <1.0 g·L-1, PT and INR revealed the highest areas under the receiver operating characteristic curve, 0.76 (95% CI, 0.55-0.97) and 0.76 (95% CI, 0.57-0.97), respectively. The highest accuracy and the highest sensitivity were provided by PT/INR. PT/INR could be used as a diagnostic test for severe hypofibrinogenemia in GPV envenomation because of its high accuracy and area under the receiver operating characteristic curve.

Cyclical Stretching Induces Excess Intracellular Ca2+ Influx in Human Keloid-Derived Fibroblasts In Vitro.

The incidence of keloids is higher in the case of darker skin. It is more common in the parts exposed to stretching (thorax, abdomen, and joints). Cyclical stretching reportedly induced each Ca2+ spike through differential mechanosensitive channels in human synovial and dermal fibroblasts. Therefore, the authors hypothesized that cyclical stretching also induces a specific Ca2+ spike in keloid-derived fibroblasts. This in vitro study compared the intracellular calcium dynamics induced by cyclical stretching between control (human dermal fibroblasts) and keloid (human keloid-derived fibroblasts) groups. Each group was exposed to two-dimensional stretch using an originally developed stretch microdevice. Intracellular Ca2+ was observed for 5 minutes, including 30 seconds of baseline, under a fluorescent confocal laser microscope. The intracellular Ca2+ concentration was evaluated every 0.5 second using the fluorescence intensity ratio. A positive cellular response was defined as a rise of the ratio by greater than or equal to 20%. The normal response cutoff value was determined by receiver operating characteristic analysis. The keloid groups were significantly more responsive than the control groups (15.7% versus 8.2%; P = 0.029). In the cellular response-positive cells, the keloid groups reached significantly higher intracellular Ca2+ concentration peaks than the control groups (2.20 versus 1.26; P = 0.0022). The cutoff value was 1.77, and 10.4% of the keloid-derived fibroblasts exhibited a hyper-Ca2+ spike above the normal range. Keloid-derived fibroblasts with a hyper-Ca2+ spike might constitute a keloid-specific subpopulation. Hereafter, the authors will study whether the normalization of excessive intracellular Ca2+ concentration leads to keloid treatment in vivo. This study result provided a clue to the onset mechanism of keloids, which the authors hope will lead to the development of new therapy in the future.

Ultrasensitive aptamer-functionalized Cu-MOF fluorescent nanozyme as an optical biosensor for detection of C-reactive protein

In the present work, an aptasensing method based on integration of RNA on Cu-MOF was developed for detection of C-Reactive Protein (CRP). Cu-MOF showed stimulated fluorescence and mimetic peroxidase enzymatic activity at the time and can be used as dual-signal transduction. CRP binding RNA was used as a highly selective recognition element and immobilized on the Cu-MOF. The immobilized RNA can block the peroxidase activity and fluorescence of the signal traducer probe. Adding CRP to the RNA/Cu-MOF will release RNA from the surface of Cu-MOF and recover both the stimulated fluorescence and peroxidase activity. A biosensor was built for detection of CRP using the two modes of transduction, either colorimetry or fluorometry. A dynamic linear range was obtained from 0.1 to 50 ng mL −1with a limit of detection (LOD) as small as 40 pg mL −1was calculated in fluorescence mode and 240 pg mL −1 as LOD in colorimetry mode. The LODs are lower than the LOD of nephelometric techniques used in clinical practice and is comparable to the normal clinical cutoff value in high-sensitivity CRP assays (1 μg/mL). The aptasensor was successfully applied for detection of CRP in Covid-19 patients with spike recoveries between 84 and 102% and RSD from 0.94% to 2.05%.

Cross-sectional survey following a longitudinal study on mental health and insomnia of people with sporadic COVID-19.

BACKGROUNDIn the post-pandemic era, the emergence of sporadic cases of coronavirus disease 2019 (COVID-19) and the scale of the pandemic are unpredictable. Therefore, the impact of sporadic cases of COVID-19 and isolation measures on mental health and sleep in different groups of people need to be analyzed. AIMTo clarify the severity of psychological problems and insomnia of staff and community residents around a hospital with sporadic cases of COVID-19, and their relationship with quarantine location and long-term changes.METHODSA cross-sectional survey was conducted on community residents and medical staff. Many of these medical staff had been subjected to different places of quarantine. Community residents did not experience quarantine. Hospital anxiety and depression scale (HADS), acute stress disorder scale (ASDS) and insomnia severity index (ISI) were used to evaluate anxiety and depression, acute stress disorder symptoms, and the severity of insomnia. Additionally, we conducted a 1-year follow-up study on medical staff, with related scales measurement immediately after and one year after the 2-wk quarantine period.RESULTSWe included 406 medical staff and 226 community residents. The total scores of ISI and subscale in HADS of community residents were significantly higher than that of medical staff. Further analysis of medical staff who experienced quarantine showed that 134 were quarantined in hotels, 70 in hospitals and 48 at home. Among all subjects, the proportions of HADS, ASDS and ISI scores above normal cutoff value were 51.94%, 19.17% and 31.11%, respectively. Multivariable logistic regression analysis found that subjects with higher total ASDS scores had a greater risk to develop anxiety and depression. The total ISI score for medical staff in hotel quarantine was significantly higher than those in home quarantine. Total 199 doctors and nurses who completed the 1-year follow-up study. Compared with baseline, HADS and ASDS scores decreased significantly one year after the end of quarantine, while ISI scores did not change significantly. CONCLUSIONSporadic COVID-19 cases had a greater psychological impact on residents in surrounding communities, mainly manifested as insomnia and depressive symptoms. Hotel quarantine aggravated the severity of insomnia in medical staff, whose symptoms lasted ≥ 1 year.

The association of aerobic, resistance, and combined exercises with the handgrip strength of middle-aged and elderly Korean adults: a nationwide cross-sectional study

BackgroundHandgrip strength (HGS), an indicator of overall muscle strength, is a key component in sarcopenia diagnosis. Although exercise is an effective strategy to prevent sarcopenia, the most appropriate exercise type targeting sarcopenia needs to be established. This study aimed to investigate the relationship between the physical activity (PA) patterns and HGS.MethodsThis was a cross-sectional study using the data from the 7th Korea National Health and Nutrition Examination Survey (2016–2018). The study population included 12,814 adults aged ≥ 40 years. According to the World Health Organization PA guidelines for public health, both aerobic (moderate to vigorous PA ≥ 150 min/week) and resistance exercises (≥ 2 sessions/week) are recommended. Study participants were categorized into one of the four groups depending on their adherence to each of two exercise guidelines (“neither,” “aerobic only,” “resistance only,” and “combined”). By defining normal HGS cutoff values as the lowest quartile of HGS from the population aged 20 years and above, we classified participants as “preserved” HGS group if their HGS was equal to or above the cutoff values. A Poisson regression model was used to calculate adjusted prevalence ratios (APRs) for preserved HGS across the four PA guideline adherences stratified by age and sex groups.ResultsIn middle-aged adults, the “combined” exercise group was independently associated with the preserved HGS (male, age 50–59 years, APR = 1.072; male, age 60–69 years, APR = 1.180; female, age 50–59 years, APR = 1.112; female, age 60–69 years, APR = 1.188). For adults aged ≥ 70 years, meeting only aerobic or resistance exercise guidelines showed a positive association with HGS before adjusting for other health-related variables. In males of ≥ 70 years, the APR of preserved HGS was highest in the “combined” exercise group (“resistance only,” APR = 1.459, “combined,” APR = 1.664), while in women aged ≥ 70 years, the significance was lost after adjusting for covariates.ConclusionsAdults meeting both aerobic and resistance exercise guidelines were associated with the highest prevalence of preserved HGS. Performing both types of exercise might be the most effective way to prevent sarcopenia that should be investigated in future clinical trials.

Index of microcirculatory resistance in the assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy

Introduction and objectivesCoronary microvascular dysfunction (CMD) is one of the most important pathophysiological features in hypertrophic cardiomyopathy (HCM). The index of microcirculatory resistance (IMR) is an invasive method to assess the coronary microcirculation. The aim was to assess CMD in patients with HCM by IMR. MethodsAdult patients with HCM without epicardial coronary artery disease underwent cardiac catheterization for the assessment of CMD by IMR (normal cut-off value ≤22.0) and coronary flow reserve (CFR) (normal cut-off value ≥2). Cardiovascular magnetic resonance (CMR) was performed to assess the ischemic burden by perfusion imaging during regadenoson-induced hyperemia, and the extent of myocardial fibrosis was assessed by late gadolinium enhancement (LGE), native T1 mapping and extracellular volume (ECV). ResultsFourteen patients were enrolled with a mean age of 62.8±6.2years, 8 (57.1%) males, of whom 9 (64.3%) had obstructive HCM. Using IMR, CMD was detected in 4 (29%) patients. Among four patients with an IMR>22.0, all had non-obstructive HCM and two had angina. CFR<2 was reported in eight patients (57%). Concordance between IMR and CFR (both normal or both abnormal) was verified in 6 patients (43%). Among four patients with IMR>22.0, perfusion defects were found in two of the three patients who underwent stress CMR. Increased ECV (>28%) was documented in two of the patients with IMR>22 and in three of the patients with IMR≤22.0. LGE was >15% in 2 of the patients with IMR>22 and in 4 with IMR≤22.0. ConclusionsIMR assessment in HCM is feasible and safe. Patients with abnormal IMR seemed to have more significant tissue abnormalities on CMR.