Mortality of elderly patients with acute kidney injury undergoing continuous renal replacement therapy: is age a risk factor?

Background: Whether advanced age is associated with poor outcomes of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is controversial. This study aimed to evaluate age effect and predictors for mortality in elderly AKI patients undergoing CRRT. Methods: Data of 480 elderly AKI patients who underwent CRRT were retrospectively analyzed. Subjects were stratified into two groups according to age: younger-old (age, 65-74 years; n = 205) and older-old (age, ≥75 years; n = 275). Predictors for 28-day and 90-day mortality and age effects were analyzed using multivariable Cox regression analysis and propensity score matching. Results: Urine output at the start of CRRT (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.99-1.00; p = 0.04), operation (aHR, 0.53; 95% CI, 0.30-0.93; p = 0.03), and use of an intra-aortic balloon pump (aHR, 3.60; 95% CI, 1.18-10.96; p = 0.02) were predictors for 28-day mortality. Ischemic heart disease (aHR, 1.74; 95% CI, 1.02-2.98; p = 0.04) and use of a ventilator (aHR, 0.56; 95% CI, 0.36-0.89; p = 0.01) were predictors for 90-day mortality. The older-old group did not exhibit a higher risk for 28-day or 90-day mortality than the younger-old group in multivariable or propensity score-matched models. Conclusion: Advanced age was not a risk factor for mortality among elderly AKI patients undergoing CRRT, suggesting that advanced age should not be considered for therapeutic decisions in critically ill elderly patients with AKI requiring CRRT.

Efficient isolation of encoded microparticles in a degassed micromold for highly sensitive and multiplex immunoassay with signal amplification.

Multiplex detection of low-abundance protein biomarkers in biofluids can contribute to diverse biomedical fields such as early diagnosis and precision medicine. However, conventional techniques such as digital ELISA, microarray, and hydrogel-based assay still face limitations in terms of efficient protein detection due to issues with multiplexing capability, sensitivity, or complicated assay procedures. In this study, we present the degassed micromold-based particle isolation technique for highly sensitive and multiplex immunoassay with enzymatic signal amplification. Using degassing treatment of nanoporous polydimethylsiloxane (PDMS) micromold, the encoded particles are isolated in the mold within 5 min absorbing trapped air bubbles into the mold by air suction capability. Through 10 min of signal amplification in the isolated spaces by fluorogenic substrate and horseradish peroxidase labeled in the particle, the assay signal is amplified with one order of magnitude compared to that of the standard hydrogel-based assay. Using the signal amplification assay, vascular endothelial growth factor (VEGF) and chorionic gonadotropin beta (CG beta), the preeclampsia-related protein biomarkers, are quantitatively detected with a limit of detection (LoD) of 249 fg/mL and 476 fg/mL in phosphate buffer saline. The multiplex immunoassay is conducted to validate negligible non-specific detection signals and robust recovery rates in the multiplex assay. Finally, the VEGF and CG beta in real urine samples are simultaneously and quantitatively detected by the developed assay. Given the high sensitivity, multiplexing capability, and process simplicity, the presented particle isolation-based signal amplification assay holds significant potential in biomedical and proteomic fields.

The effect of preoperative botulinum toxin a injection on traction force during hernia repair: a prospective, single-blind study, intra-patient comparison using contralateral side as a control.

PURPOSE: Ventral hernias are a common complication of laparotomy, posing challenges particularly when primary fascial closure is unattainable. Although chemical component separation using preoperative botulinum toxin A (BTX) injections has emerged as a promising adjunct, objective evidence of its efficacy remains limited. This study aimed to objectively assess the effect of preoperative BTX on traction force during ventral hernia repair. METHODS: A prospective, single-blind study was conducted on patients with midline incisional hernias following liver transplantation. BTX was administered unilaterally, and the traction force required to medially advance the anterior rectus sheath was measured intraoperatively. Pre- and post-injection CT scans were analyzed for changes in hernia size and LAW muscle measurements. Statistical analyses were performed to evaluate traction force differences between BTX-injected and uninjected sides. RESULTS: Ten patients underwent hernia repair with primary fascial closure achieved in all cases. Comparison of pre- and post-injection CT scans showed no significant changes in hernia size. LAW muscle length increased by 1.8 cm, while thickness decreased by 0.2 cm. Intraoperative traction force measurements revealed a significant reduction on the BTX-injected side compared to the uninjected side (p < 0.0001). The traction force ratio on the BTX-injected to the uninjected side averaged 57%, indicating the efficacy of BTX in reducing tension. CONCLUSION: Preoperative BTX significantly reduces traction force during ventral hernia repair, highlighting its potential as an adjunctive therapy in complex cases. While challenges remain in patient selection and outcome assessment, BTX offers a promising avenue for enhancing abdominal wall reconstruction outcomes and reducing surgical complications.

Lipedema associated with Skin Hypoperfusion and Ulceration: Soft Tissue Debulking Improving Skin Perfusion.

Lipedema is a progressive connective tissue disease with enlargement of adipose tissue, fibrosis, fluid collection, and dermal thickening. Herein, we present a case of lipedema associated with skin hypoperfusion and ulceration in which soft tissue debulking with liposuction improved patients' symptoms. A 39-year-old female presented with asymmetric progressive initially unilateral lower limb swelling with severe pain with subsequent skin ulceration. Conservative management failed to improve her condition. After excluding other causes and detailed radiologic investigation, lipedema was diagnosed with an associated impaired skin perfusion. Trial of local wound care and compression therapy failed to improve the condition. Subsequent soft tissue debulking with circumferential liposuction and ulcer debridement and immediate compression showed dramatic improvement of the symptoms and skin perfusion. The unique nature of this case sheds light on lipedema as a loose connective tissue disease. Inflammation and microangiopathies explain the associated pain with hypoperfusion and ulceration being quite atypical and in part might be related to the large buildups of matrix proteins and sodium contents leading to fragility in microvessels with frequent petechiae and hematoma and subsequent tissue ischemia. Conservative measures like compression therapy plays a significant role in disease course. Surgical debulking with liposuction was shown to be efficacious in reducing the soft tissue load with improvement in limb pain, edema, circumference, and skin perfusion that was seen in our patient. Lipedema is a frequently misdiagnosed condition with disabling features. Skin involvement in lipedema with potential hypoperfusion was shown and it requires further investigation.

Stress hyperglycemia exacerbates inflammatory brain injury after stroke.

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47 phox-/- mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.

Split fluorescent protein-mediated multimerization of cell wall binding domain for highly sensitive and selective bacterial detection.

Cell wall peptidoglycan binding domains (CBDs) of cell lytic enzymes, including bacteriocins, autolysins and bacteriophage endolysins, enable highly selective bacterial binding, and thus, have potential as biorecognition molecules for nondestructive bacterial detection. Here, a novel design for a self-complementing split fluorescent protein (FP) complex is proposed, where a multimeric FP chain fused with specific CBDs ((FP-CBD)n) is assembled inside the cell, to improve sensitivity by enhancing the signal generated upon Staphylococcus aureus or Bacillus anthracis binding. Flow cytometry shows enhanced fluorescence on the cell surface with increasing FP stoichiometry and surface plasmon resonance reveals nanomolar binding affinity to isolated peptidoglycan. The breadth of function of these complexes is demonstrated through the use of CBD modularity and the ability to attach enzymatic detection modalities. Horseradish peroxidase-coupled (FP-CBD)n complexes generate a catalytic amplification, with the degree of amplification increasing as a function of FP length, reaching a limit of detection (LOD) of 103 cells/droplet (approximately 0.1 ng S. aureus or B. anthracis) within 15 min on a polystyrene surface. These fusion proteins can be multiplexed for simultaneous detection. Multimeric split FP-CBD fusions enable use as a biorecognition molecule with enhanced signal for use in bacterial biosensing platforms.

α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway.

Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic dysfunction is linked to cognitive deficits in LBD. Here, we investigated the pathological impact of αSyn on hippocampal neurons. We report that either αSyn overexpression or αSyn pre-formed fibrils (PFFs) treatment triggers the formation of cofilin-actin rods, synapse disruptors, in cultured hippocampal neurons and in the hippocampus of synucleinopathy mouse models and of LBD patients. In vivo, cofilin pathology is present concomitantly with synaptic impairment and cognitive dysfunction. Rods generation prompted by αSyn involves the co-action of the cellular prion protein (PrPC) and the chemokine receptor 5 (CCR5). Importantly, we show that CCR5 inhibition, with a clinically relevant peptide antagonist, reverts dendritic spine impairment promoted by αSyn. Collectively, we detail the cellular and molecular mechanism through which αSyn disrupts hippocampal synaptic structure and we identify CCR5 as a novel therapeutic target to prevent synaptic impairment and cognitive dysfunction in LBD.

Autonomous Synthesis of Thin Film Materials with Pulsed Laser Deposition Enabled by In Situ Spectroscopy and Automation.

Autonomous systems that combine synthesis, characterization, and artificial intelligence can greatly accelerate the discovery and optimization of materials, however platforms for growth of macroscale thin films by physical vapor deposition techniques have lagged far behind others. Here this study demonstrates autonomous synthesis by pulsed laser deposition (PLD), a highly versatile synthesis technique, in the growth of ultrathin WSe2 films. By combing the automation of PLD synthesis and in situ diagnostic feedback with a high-throughput methodology, this study demonstrates a workflow and platform which uses Gaussian process regression and Bayesian optimization to autonomously identify growth regimes for WSe2 films based on Raman spectral criteria by efficiently sampling 0.25% of the chosen 4D parameter space. With throughputs at least 10x faster than traditional PLD workflows, this platform and workflow enables the accelerated discovery and autonomous optimization of the vast number of materials that can be synthesized by PLD.

Real-Time Signal Analysis with Wider Dynamic Range and Enhanced Sensitivity in Multiplex Colorimetric Immunoassays Using Encoded Hydrogel Microparticles.

The simultaneous quantification of multiple proteins is crucial for accurate medical diagnostics. A promising technology, the multiplex colorimetric immunoassay using encoded hydrogel microparticles, has garnered attention, due to its simplicity and multiplex capabilities. However, it encounters challenges related to its dynamic range, as it relies solely on the colorimetric signal analysis of encoded hydrogel microparticles at the specific time point (i.e., end-point analysis). This necessitates the precise determination of the optimal time point for the termination of the colorimetric reaction. In this study, we introduce real-time signal analysis to quantify proteins by observing the continuous colorimetric signal change within the encoded hydrogel microparticles. Real-time signal analysis measures the "slope", the rate of the colorimetric signal generation, by focusing on the kinetics of the accumulation of colorimetric products instead of the colorimetric signal that appears at the end point. By developing a deep learning-based automatic analysis program that automatically reads the code of the graphically encoded hydrogel microparticles and obtains the slope by continuously tracking the colorimetric signal, we achieved high accuracy and high throughput analysis. This technology has secured a dynamic range more than twice as wide as that of the conventional end-point signal analysis, simultaneously achieving a sensitivity that is 4-10 times higher. Finally, as a demonstration of application, we performed multiplex colorimetric immunoassays using real-time signal analysis covering a wide concentration range of protein targets associated with pre-eclampsia.

Efficacy and Safety of PrabotulinumtoxinA in Subjects With Benign Masseteric Hypertrophy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase 3 Trial and Open-Label Extension Study.

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.

Selected Area Manipulation of MoS2 via Focused Electron Beam-Induced Etching for Nanoscale Device Editing.

We demonstrate direct-write patterning of single and multilayer MoS2 via a focused electron beam-induced etching (FEBIE) process mediated with the XeF2 precursor. MoS2 etching is performed at various currents, areal doses, on different substrates, and characterized using scanning electron and atomic force microscopies as well as Raman and photoluminescence spectroscopies. Scanning transmission electron microscopy reveals a sub-40 nm etching resolution and the progression of point defects and lateral etching of the consequent unsaturated bonds. The results confirm that the electron beam-induced etching process is minimally invasive to the underlying material in comparison to ion beam techniques, which damage the subsurface material. Single-layer MoS2 field-effect transistors are fabricated, and device characteristics are compared for channels that are edited via the selected area etching process. The source-drain current at constant gate and source-drain voltage scale linearly with the edited channel width. Moreover, the mobility of the narrowest channel width decreases, suggesting that backscattered and secondary electrons collaterally affect the periphery of the removed area. Focused electron beam doses on single-layer transistors below the etching threshold were also explored as a means to modify/thin the channel layer. The FEBIE exposures showed demonstrative effects via the transistor transfer characteristics, photoluminescence spectroscopy, and Raman spectroscopy. While strategies to minimize backscattered and secondary electron interactions outside of the scanned regions require further investigation, here, we show that FEBIE is a viable approach for selective nanoscale editing of MoS2 devices.

Ultrahigh Photosensitivity Based on Single-Step Lay-on Integration of Freestanding Two-Dimensional Transition-Metal Dichalcogenide.

Two-dimensional transition-metal dichalcogenides have attracted significant attention because of their unique intrinsic properties, such as high transparency, good flexibility, atomically thin structure, and predictable electron transport. However, the current state of device performance in monolayer transition-metal dichalcogenide-based optoelectronics is far from commercialization, because of its substantial strain on the heterogeneous planar substrate and its robust metal deposition, which causes crystalline damage. In this study, we show that strain-relaxed and undamaged monolayer WSe2 can improve a device performance significantly. We propose here an original point-cell-type photodetector. The device consists in a monolayer of an absorbing TMD (i.e., WSe2) simply deposited on a structured electrode, i.e., core-shell silicon-gold nanopillars. The maximum photoresponsivity of the device is found to be 23.16 A/W, which is a significantly high value for monolayer WSe2-based photodetectors. Such point-cell photodetectors can resolve the critical issues of 2D materials, leading to tremendous improvements in device performance.

Application of augmented reality using automatic markerless registration for facial plastic and reconstructive surgery.

This study aimed to present a novel markerless augmented reality (AR) system using automatic registration based on machine-learning algorithms that visualize the facial region and provide an intraoperative guide for facial plastic and reconstructive surgeries. This study prospectively enrolled 20 patients scheduled for facial plastic and reconstructive surgeries. The AR system visualizes computed tomographic data in three-dimensional (3D) space by aligning with the point clouds captured by a 3D camera. Point cloud registration consists of two stages: the preliminary registration gives an initial estimate of the transformation using landmark detection, followed by the precise registration using Iterative Closest Point algorithms. Computed Tomography (CT) data can be visualized as two-dimensional slice images or 3D images by the AR system. The AR registration error was defined as the cloud-to-cloud distance between the surface data obtained from the CT and 3D camera. The error was calculated in each facial territory, including the upper, middle, and lower face, while patients were awake and orally intubated, respectively. The mean registration errors were 1.490 ± 0.384 mm and 1.948 ± 0.638 mm while patients were awake and orally intubated, respectively. There was a significant difference in the errors in the lower face between patients while they were awake (1.502 ± 0.480 mm) and orally intubated (2.325 ± 0.971 mm) when stratified by facial territories (p = 0.006). The markerless AR can accurately visualize the facial region with a mean overall registration error of 1-2 mm, with a slight increase in the lower face due to errors arising from tube intubation.

Are Surprise Questions and Probabilistic Questions by Nurses Useful in Home Palliative Care? A Prospective Study.

Background: Surprise questions (SQs) are used as screening tools in palliative care. Probabilistic questions (PQs) are more accurate than temporal predictions. However, no study has examined the usefulness of SQs and PQs assessed by nurses. Objectives: To examine the accuracy of nurses' SQ and PQ assessments in patients with advanced cancer receiving home palliative care. Design: A prospective single-center cohort study. Setting/Subjects: Adult patients with advanced cancer who received palliative care at home in South Korea between 2019 and 2020. Measurements: Palliative care specialized nurses were asked the SQ, "Would you be surprised if the patient died in a specific timeframe?" and PQ, "What is the probability that this patient will be alive (0 to 100%) within a specific timeframe?" at the 1-, 2-, 4-, and 6-week timeframes at enrollment. We calculated the sensitivities and specificities of the SQs and PQs. Results: 81 patients were recruited with 47 days of median survival. The sensitivity, specificity, and overall accuracy (OA) of the 1-week SQ were 50.0, 93.2, and 88.9%, respectively. The accuracies for the 1-week PQ were 12.5, 100.0, and 91.3%, respectively. The 6-week SQ showed sensitivity, specificity, and OA of 84.6, 42.9, and 62.9%, respectively; the accuracies for the 6-week PQ were 59.0, 66.7, and 63.0%, respectively.Conclusion: The SQ and PQ showed acceptable accuracy in home palliative care patients. Interestingly, PQ showed higher specificity than SQ at all timeframes. The SQ and PQ assessed by nurses may be useful in providing additional prognostic information for home palliative care.

Exosomes derived from human dermal fibroblasts (HDFn-Ex) alleviate DNCB-induced atopic dermatitis (AD) via PPARα.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Recently, exosomes have been considered as potential cell-free medicine for skin defects such as aging, psoriasis and wounds. The aim of this study was to investigate the effects of human dermal fibroblast-neonatal-derived exosome (HDFn-Ex) on AD. HDFn-Ex increased the expression of peroxisome proliferator activated receptor α (PPARα) and alleviated the 1-chloro-2,4-dinitrobenzene (DNCB)-mediated downregulation of filaggrin, involucrin, loricrin, hyaluronic acid synthase 1 (HAS1) and HAS2 in human keratinocyte HaCaT cells. However, these effects were inhibited by the PPARα antagonist GW6471. In the artificial skin model, HDFn-Ex significantly inhibited DNCB-induced epidermal hyperplasia and the decrease in filaggrin and HAS1 levels via a PPARα. In the DNCB-induced AD-like mouse model, HDFn-Ex administration reduced epidermis thickening and mast cell infiltration into the dermis compared to DNCB treatment. Moreover, the decreases in PPARα, filaggrin and HAS1 expression, as well as the increases in IgE and IL4 levels induced by DNCB treatment were reversed by HDFn-Ex. These effects were blocked by pre-treatment with GW6471. Furthermore, HDFn-Ex exhibited an anti-inflammatory effect by inhibiting the DNCB-induced increases in IκBα phosphorylation and TNF-α expression. Collectively, HDFn-Ex exhibited a protective effect on AD. Notably, these effects were regulated by PPARα. Based on our results, we suggest that HDFn-Ex is a potential candidate for treating AD by recovering skin barrier dysfunction and exhibiting anti-inflammatory activity.

p-Phenylenediamine-Bridged Binder-Electrolyte-Unified Supramolecules for Versatile Lithium Secondary Batteries.

The binder is an essential component in determining the structural integrity and ionic conductivity of Li-ion battery electrodes. However, conventional binders are not sufficiently conductive and durable to be used with solid-state electrolytes. In this study, a novel system is proposed for a Li secondary battery that combines the electrolyte and binder into a unified structure, which is achieved by employing para-phenylenediamine (pPD) moiety to create supramolecular bridges between the parent binders. Due to a partial crosslinking effect and charge-transferring structure of pPD, the proposed strategy improves both the ionic conductivity and mechanical properties by a factor of 6.4 (achieving a conductivity of 3.73 × 10-4 S cm-1 for poly(ethylene oxide)-pPD) and 4.4 (reaching a mechanical strength of 151.4 kPa for poly(acrylic acid)-pPD) compared to those of conventional parent binders. As a result, when the supramolecules of pPD are used as a binder in a pouch cell with a lean electrolyte loading of 2 µL mAh-1 , a capacity retention of 80.2% is achieved even after 300 cycles. Furthermore, when it is utilized as a solid-state electrolyte, an average Coulombic efficiency of 99.7% and capacity retention of 98.7% are attained under operations at 50 °C without external pressure or a pre-aging process.

Comparison of Simplified Palliative Prognostic Index and Palliative Performance Scale in Patients with Advanced Cancer in a Home Palliative Care Setting.

Objective: The Palliative Performance Scale (PPS) has been reported to be as accurate as Palliative Prognostic Index (PPI). PPS is a component of the simplified PPI (sPPI). It is unknown whether PPS is as accurate as sPPI. This study aimed to compare the prognostic performance of the PPS and sPPI in patients with advanced cancer in a home palliative care setting in South Korea. Methods: This was a secondary analysis of a prospective cohort study that included Korean patients with advanced cancer who received home-based palliative care. We used the medical records maintained by specialized palliative care nurses. We computed the prognostic performance of PPS and sPPI using the area under the receiver operating characteristic curve (AUROC) and calibration plots for the 3- and 6-week survival. Results: A total of 80 patients were included, with a median overall survival of 47.0 days. The AUROCs of PPS were 0.71 and 0.69 at the 3- and 6-week survival predictions, respectively. The AUROCs of sPPI were 0.87 and 0.73 at the 3- and 6-week survival predictions, respectively. The calibration plot demonstrated satisfactory agreement across all score ranges for both the PPS and sPPI. Conclusions: This study showed that the sPPI assessed by nurses was more accurate than the PPS in a home palliative care setting in predicting the 3-week survival in patients with advanced cancer. The PPS can be used for a quick assessment.

Efficacy and safety of a novel 785 nm picosecond neodymium-doped yttrium aluminum garnet laser for the treatment of facial benign pigmented lesions in Asian skin: a pilot study.

BACKGROUND AND OBJECTIVES: Benign pigmented lesions and a general uneven tone in people with skin of color are growing issues that have been presented to dermatologists. To the best of our knowledge, this is the first controlled study to examine the efficacy and safety of using the newly introduced 785 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) picosecond laser to treat facial benign pigmented lesions in Asian patients with diffractive lens array. MATERIALS AND METHODS: A 785 nm Nd:YAG picosecond laser was used to treat 15 healthy female volunteers older than 18 years who had Fitzpatrick skin types II-IV and facial benign pigmented lesions. Each volunteer received five weekly treatments in dual modes. The clinical improvement was assessed by independent investigators and by objectively measuring the melanin index. RESULTS: After the treatment, the melanin and erythema indices decreased, and the pigmented lesions showed clinical improvements. No serious adverse effects were observed during the study period. CONCLUSIONS: A 785 nm Nd:YAG picosecond laser may be safe and effective in treating facial benign pigmented lesions in Asian skin.

How different are accuracies of clinicians' prediction of survival by assessment methods?

BACKGROUND: No standardized method has been established for evaluating the accuracy of a clinicians' prediction of survival (CPS). Till now, no study has compared the accuracy of CPS according to the evaluation methods using the same dataset. We aimed to examine the accuracy of CPS by different statistical approaches in patients with far-advanced cancer. METHODS: The current study was a secondary analysis of an international multicenter prospective cohort study. Newly admitted patients with advanced cancer were enrolled in palliative care units (PCUs) in Japan, Korea, and Taiwan. We obtained the temporal CPS at enrollment. The patients were classified into groups of days (≤7 days) and weeks (≤30 days) based on CPS and actual survival (AS). We evaluated the accuracy of CPS by the distribution, area under the receiver operating characteristics curve (AUROCs), and an estimate ±33% of AS. RESULTS: A total of 2,571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. As for the "days" category, the distribution of AS is larger than that of CPS, however, the results are reversed in the "weeks" category. The AUROCs showed over 80% discrimination for both the "days" and "weeks" categories. Accurate CPS within ±33% of AS was approximately 30% in both "days" and "weeks" categories. CONCLUSIONS: We showed a discrepancy of approximately 30-80% in the accuracy of CPS among three different analysis methods: distribution, AUROC, and AS comparison. Considering the low accuracy of AS comparisons, clinicians should provide a wide range of survival time. CPS was able to effectively discriminate and may be useful for risk stratification.

Ultrasensitive ImmunoMag-CRISPR Lateral Flow Assay for Point-of-Care Testing of Urinary Biomarkers.

Rapid, accurate, and noninvasive detection of biomarkers in saliva, urine, or nasal fluid is essential for the identification, early diagnosis, and monitoring of cancer, organ failure, transplant rejection, vascular diseases, autoimmune disorders, and infectious diseases. We report the development of an Immuno-CRISPR-based lateral flow assay (LFA) using antibody-DNA barcode complexes with magnetic enrichment of the target urinary biomarkers CXCL9 and CXCL10 for naked eye detection (ImmunoMag-CRISPR LFA). An intermediate approach involving a magnetic bead-based Immuno-CRISPR assay (ImmunoMag-CRISPR) resulted in a limit of detection (LOD) of 0.6 pg/mL for CXCL9. This value surpasses the detection limits achieved by previously reported assays. The highly sensitive detection method was then re-engineered into an LFA format with an LOD of 18 pg/mL for CXCL9, thereby enabling noninvasive early detection of acute kidney transplant rejection. The ImmunoMag-CRISPR LFA was tested on 42 clinical urine samples from kidney transplant recipients, and the assay could determine 11 positive and 31 negative urinary samples through a simple visual comparison of the test line and the control line of the LFA strip. The LFA system was then expanded to quantify the CXCL9 and CXCL10 levels in clinical urine samples from images. This approach has the potential to be extended to a wide range of point-of-care tests for highly sensitive biomarker detection.