Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assays, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mTOR signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.

Characteristics and Outcomes of Prolonged Venoarterial Extracorporeal Membrane Oxygenation After Cardiac Surgery: The Post-Cardiotomy Extracorporeal Life Support (PELS-1) Cohort Study.

OBJECTIVES: Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO. DESIGN: Retrospective observational cohort study. SETTING: Thirty-four centers from 16 countries between January 2000 and December 2020. PATIENTS: Adults requiring post PC ECMO between 2000 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days (n = 649 [32.1%]), 4-7 days (n = 776 [38.3%]), 8-10 days (n = 263 [13.0%]), and greater than 10 days (n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days (n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support (n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival. CONCLUSIONS: Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration.

Interactive effects of exercise intensity and recovery posture on postexercise hypotension.

Postexercise reduction in blood pressure, termed postexercise hypotension (PEH), is relevant for both acute and chronic health reasons and potentially for peripheral cardiovascular adaptations. We investigated the interactive effects of exercise intensity and recovery postures (seated, supine, and standing) on PEH. Thirteen normotensive men underwent a V̇o2max test on a cycle ergometer and five exhaustive constant load trials to determine critical power (CP) and the gas exchange threshold (GET). Subsequently, work-matched exercise trials were performed at two discrete exercise intensities (10% > CP and 10% < GET), with 1 h of recovery in each of the three postures. For both exercise intensities, standing posture resulted in a more substantial PEH (all P < 0.01). For both standing and seated recovery postures, the higher exercise intensity led to larger reductions in systolic [standing: -33 (11) vs. -21 (8) mmHg; seated: -34 (32) vs. -17 (37) mmHg, P < 0.01], diastolic [standing: -18 (7) vs. -8 (5) mmHg; seated: -10 (10) vs. -1 (4) mmHg, P < 0.01], and mean arterial pressures [-13 (8) vs. -2 (4) mmHg, P < 0.01], whereas in the supine recovery posture, the reduction in diastolic [-9 (9) vs. -4 (3) mmHg, P = 0.08) and mean arterial pressures [-7 (5) vs. -3 (4) mmHg, P = 0.06] was not consistently affected by prior exercise intensity. PEH is more pronounced during recovery from exercise performed above CP versus below GET. However, the effect of exercise intensity on PEH is largely abolished when recovery is performed in the supine posture.NEW & NOTEWORTHY The magnitude of postexercise hypotension is greater following the intensity above the critical power in a standing position.

Short (≤6 mm) compared with ≥10-mm dental implants in different clinical scenarios: A systematic review of randomized clinical trials with meta-analysis, trial sequential analysis and quality of evidence grading.

AIM: To systematically identify, synthesize and critically summarize the available scientific evidence from randomized controlled trials (RCTs) regarding whether short (≤6 mm) perform as well as long (≥10 mm) implants regarding implant survival, marginal bone loss, and biologic and prosthetic complications in different clinical scenarios. MATERIALS AND METHODS: Cochrane Collaboration's risk of bias tool and the GRADE approach were applied. Results were synthesized using random-effects meta-analyses assessed by trial sequential analyses. RESULTS: Forty reports on 19 RCTs comprising 2214 (1097 short; 1117 long) implants were included. Moderate/high certainty/quality evidence demonstrated similar 5-year survival rates for ≤6-mm and ≥10-mm implants in non-augmented bone and full-mouth rehabilitation in either jaw, and for 6-mm implants in the maxilla instead of sinus lift. Nevertheless, the evidence for 5-year survival rates remains inconclusive or insufficient for the remaining combinations of implant lengths and clinical scenarios. They include 4-mm and 5-mm implants as alternatives to sinus lift as well as placing all implant lengths ≤6 mm instead of vertical ridge augmentation with long implants. Marginal bone level and short- and long-term biologic or prosthetic complications were similar. CONCLUSIONS: Based on moderate/high certainty/quality evidence from 5-year RCTs, implants ≤6 mm may be viable alternatives to ≥10-mm implants in either jaw in native bone and full-arch rehabilitation, and 6-mm implants may be used as an alternative to sinus lift. TRIAL REGISTRATION: PROSPERO ID: CRD42021254365.

Development of AAV-delivered broadly neutralizing anti-human ACE2 antibodies against SARS-CoV-2 variants.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.

Post-cardiotomy extracorporeal life support: A cohort of cannulation in the general ward.

OBJECTIVES: Post-cardiotomy extracorporeal life support (ECLS) cannulation might occur in a general post-operative ward due to emergent conditions. Its characteristics have been poorly reported and investigated This study investigates the characteristics and outcomes of adult patients receiving ECLS cannulation in a general post-operative cardiac ward. METHODS: The Post-cardiotomy Extracorporeal Life Support (PELS) is a retrospective (2000-2020), multicenter (34 centers), observational study including adult patients who required ECLS for post-cardiotomy shock. This PELS sub-analysis analyzed patients´ characteristics, in-hospital outcomes, and long-term survival in patients cannulated for veno-arterial ECLS in the general ward, and further compared in-hospital survivors and non-survivors. RESULTS: The PELS study included 2058 patients of whom 39 (1.9%) were cannulated in the general ward. Most patients underwent isolated coronary bypass grafting (CABG, n = 15, 38.5%) or isolated non-CABG operations (n = 20, 51.3%). The main indications to initiate ECLS included cardiac arrest (n = 17, 44.7%) and cardiogenic shock (n = 14, 35.9%). ECLS cannulation occurred after a median time of 4 (2-7) days post-operatively. Most patients' courses were complicated by acute kidney injury (n = 23, 59%), arrhythmias (n = 19, 48.7%), and postoperative bleeding (n = 20, 51.3%). In-hospital mortality was 84.6% (n = 33) with persistent heart failure (n = 11, 28.2%) as the most common cause of death. No peculiar differences were observed between in-hospital survivors and nonsurvivors. CONCLUSIONS: This study demonstrates that ECLS cannulation due to post-cardiotomy emergent adverse events in the general ward is rare, mainly occurring in preoperative low-risk patients and after a postoperative cardiac arrest. High complication rates and low in-hospital survival require further investigations to identify patients at risk for such a complication, optimize resources, enhance intervention, and improve outcomes.

The 2017 Women's Health Initiative study and use of hormone therapy: an emulated repeated cross-sectional study.

BACKGROUND: Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan. METHODS: We identified 1,869,050 women aged 50-60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design. RESULTS: Study participants' baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use. CONCLUSIONS: The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.

Ultrasonography-Derived Elasticity Estimation of Live Porcine Oral Mucosa.

OBJECTIVES: To investigate the biomechanical properties of porcine oral tissues with in vivo ultrasonography and to compare the difference between oral alveolar mucosa and gingival tissue concerning compressional and tensile mechanical strain. MATERIALS AND METHODS: Sinclair minipigs (6 females and 4 males, 6 to 18 months of age) were anesthetized for ultrasonography. In vivo high-frequency tissue harmonic ultrasound (12/24 MHz) cine-loops were obtained while inducing mechanical tissue stress (0 to 1 N). Post-processing strain analysis was performed in a cardiac speckle tracking software (EchoInsight®). Region of interest (ROI) was placed for gingival and alveolar mucosa tissues for longitudinal (compressional) and tensile strain analyses. A calibrated gel pad was employed to determine the absolute force (pressure) for the measured tissue strain response function. The resulting elasticity data was statistically analyzed using custom Matlab scripts. RESULTS: In total, 38 sonography cine-loops around the third premolars were included in the investigation. The longitudinal strain of alveolar mucosa ε AM L was found to be significantly (P < .05) larger than that of gingiva ε G L . Across the measured force range, ε AM L ~ 1.7 × Îµ G L . Significant differences between alveolar mucosa and gingiva tissues were found for all forces. The tensile strain of the alveolar mucosa ε AM T was found to be ~2 × Îµ G T (on the epithelial surface of the gingiva). Both were statistically significantly different for forces exceeding ~0.08 N. At depth, that is, 500 and 1000 µm below the epithelial surface, the gingiva was found to have less ability to stretch contrary to the alveolar mucosa. Gingival tissue at 500 µm depth has significantly less tensile strain than at its surface and more than at 1000 µm depth. In contrast, the tensile strain of alveolar mucosa is largely independent of depth. CONCLUSION: Ultrasonography can reveal significant differences in oral alveolar mucosal and gingival elastic properties, such as compressional and tensile strain. Under minute forces equivalent to 10 to 40 g, these differences can be observed. As dental ultrasound is a chairside, and noninvasive modality, obtaining real-time images might soon find clinical utility as a new diagnostic tool for the objective and quantitative assessment of periodontal and peri-implant soft tissues in clinical and research realms. As ultrasound is a safe modality with no known bioeffects, longitudinal monitoring of areas of concern would be particularly attractive.

Efficacy and safety of enteral supplementation with high-dose vitamin D in critically ill patients with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.

Diabetes self-management education on the sustainability of metabolic control in type 2 diabetes patients: Diabetes share care program in Taiwan.

BACKGROUND: Diabetes self-management education (DSME) improves glycemic and metabolic control. However, the frequency, duration and sustainability of DSME for improving metabolic control have not been well studied. METHODS: The Diabetes Share Care Program (DSCP) stage 1 provided DSME every 3 months. If participants entering DSCP stage 1 ≥ 2 years and HbA1c < 7%, they can be transferred to stage 2 (DSME frequency: once a year). Three-to-one matching between DSCP stage 1 and stage 2 groups based on the propensity score method to match the two groups in terms of HbA1c and diabetes duration. We identified 311 people living with type 2 diabetes in DSCP stage 1 and 86 in stage 2 and evaluated their metabolic control and healthy behaviors annually for 5 years. RESULTS: In the first year, HbA1c in the DSCP stage 2 group was significantly lower than that in the stage 1 group. In the first and the fifth years, the percentage of patients achieving HbA1c < 7% was significantly higher in the DSCP stage 2 group than the stage 1 group. There was no significant difference in other metabolic parameters between the two groups during the 5-year follow-up. Self-monitoring of blood glucose (SMBG) frequency was associated with a reduced HbA1c after 5 years (95% CI: -0.0665 to -0.0004). CONCLUSION: We demonstrated sustainable effects of at least 2-year DSME on achieving better glycemic control for at least 1 year. SMBG contributed to improved glycemic control. The results may be applied to the reimbursement strategy in diabetes education.

Cell size and actin architecture determine force generation in optogenetically activated cells.

Adherent cells use actomyosin contractility to generate mechanical force and to sense the physical properties of their environment, with dramatic consequences for migration, division, differentiation, and fate. However, the organization of the actomyosin system within cells is highly variable, with its assembly and function being controlled by small GTPases from the Rho family. To understand better how activation of these regulators translates into cell-scale force generation in the context of different physical environments, here we combine recent advances in non-neuronal optogenetics with micropatterning and traction force microscopy on soft elastic substrates. We find that, after whole-cell RhoA activation by the CRY2/CIBN optogenetic system with a short pulse of 100 ms, single cells contract on a minute timescale in proportion to their original traction force, before returning to their original tension setpoint with near perfect precision, on a longer timescale of several minutes. To decouple the biochemical and mechanical elements of this response, we introduce a mathematical model that is parametrized by fits to the dynamics of the substrate deformation energy. We find that the RhoA response builds up quickly on a timescale of 20 s, but decays slowly on a timescale of 50 s. The larger the cells and the more polarized their actin cytoskeleton, the more substrate deformation energy is generated. RhoA activation starts to saturate if optogenetic pulse length exceeds 50 ms, revealing the intrinsic limits of biochemical activation. Together our results suggest that adherent cells establish tensional homeostasis by the RhoA system, but that the setpoint and the dynamics around it are strongly determined by cell size and the architecture of the actin cytoskeleton, which both are controlled by the extracellular environment.

Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.

Inhibition of Rho-associated protein kinase activity enhances oxidative phosphorylation to support corneal endothelial cell migration.

Corneal endothelial cell (CEC) dysfunction causes corneal edema and severe visual impairment that require transplantation to restore vision. To address the unmet need of organ shortage, descemetorhexis without endothelial keratoplasty has been specifically employed to treat early stage Fuchs endothelial corneal dystrophy, which is pathophysiologically related to oxidative stress and exhibits centrally located corneal guttae. After stripping off central Descemet's membrane, rho-associated protein kinase (ROCK) inhibitor has been found to facilitate CEC migration, an energy-demanding task, thereby achieving wound closure. However, the correlation between ROCK inhibition and the change in bioenergetic status of CECs remained to be elucidated. Through transcriptomic profiling, we found that the inhibition of ROCK activity by the selective inhibitor, ripasudil or Y27632, promoted enrichment of oxidative phosphorylation (OXPHOS) gene set in bovine CECs (BCECs). Functional analysis revealed that ripasudil, a clinically approved anti-glaucoma agent, enhanced mitochondrial respiration, increased spare respiratory capacity, and induced overexpression of electron transport chain components through upregulation of AMP-activated protein kinase (AMPK) pathway. Accelerated BCEC migration and in vitro wound healing by ripasudil were diminished by OXPHOS and AMPK inhibition, but not by glycolysis inhibition. Correspondingly, lamellipodial protrusion and actin assembly that were augmented by ripasudil became reduced with additional OXPHOS or AMPK inhibition. These results indicate that ROCK inhibition induces metabolic reprogramming toward OXPHOS to support migration of CECs.

Human ACE2 protein is a molecular switch controlling the mode of SARS-CoV-2 transmission.

BACKGROUND: Human angiotensin-converting enzyme 2 (hACE2) is the receptor mediating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. hACE2 expression is low in the lungs and is upregulated after SARS-CoV-2 infection. How such a hACE2-limited pulmonary environment supports efficient virus transmission and how dynamic hACE2 expression affects SARS-CoV-2 infection are unclear. METHODS: We generated stable cell lines with different expression levels of hACE2 to evaluate how the hACE2 expression level can affect SARS-CoV-2 transmission. RESULTS: We demonstrated that the hACE2 expression level controls the mode of SARS-CoV-2 transmission. The hACE2-limited cells have an advantage for SARS-CoV-2 shedding, which leads to cell-free transmission. By contrast, enhanced hACE2 expression facilitates the SARS-CoV-2 cell-to-cell transmission. Furthermore, this cell-to-cell transmission is likely facilitated by hACE2-containing vesicles, which accommodate numerous SARS-CoV-2 virions and transport them to neighboring cells through intercellular extensions. CONCLUSIONS: This hACE2-mediated switch between cell-free and cell-to-cell transmission routes provides SARS-CoV-2 with advantages for either viral spread or evasion of humoral immunity, thereby contributing to the COVID-19 pandemic and pathogenesis.

Critical power is a key threshold determining the magnitude of post-exercise hypotension in non-hypertensive young males.

The effect of different exercise intensities on the magnitude of post-exercise hypotension has not been rigorously clarified with respect to the metabolic thresholds that partition discrete exercise intensity domains (i.e., critical power and the gas exchange threshold (GET)). We hypothesized that the magnitude of post-exercise hypotension would be greater following isocaloric exercise performed above versus below critical power. Twelve non-hypertensive men completed a ramp incremental exercise test to determine maximal oxygen uptake and the GET, followed by five exhaustive constant load trials to determine critical power and W' (work available above critical power). Subsequently, criterion trials were performed at four discrete intensities matched for total work performed (i.e., isocaloric) to determine the impact of exercise intensity on post-exercise hypotension: 10% above critical power (10% > CP), 10% below critical power (10% < CP), 10% above GET (10% > GET) and 10% below GET (10% < GET). The post-exercise decrease (i.e., the minimum post-exercise values) in mean arterial (10% > CP: -12.7 ± 8.3 vs. 10% < CP: v3.5 ± 2.9 mmHg), diastolic (10% > CP: -9.6 ± 9.8 vs. 10% < CP: -1.4 ± 5.0 mmHg) and systolic (10% > CP: -23.8 ± 7.0 vs. 10% < CP: -9.9 ± 4.3 mmHg) blood pressures were greater following exercise performed 10% > CP compared to all other trials (all P < 0.01). No effects of exercise intensity on the magnitude of post-exercise hypotension were observed during exercise performed below critical power (all P > 0.05). Critical power represents a threshold above which the magnitude of post-exercise hypotension is greatly augmented. NEW FINDINGS: What is the central questions of this study? What is the influence of exercise intensity on the magnitude of post-exercise hypotension with respect to metabolic thresholds? What is the main finding and its importance? The magnitude of post-exercise hypotension is greatly increased following exercise performed above critical power. However, below critical power, there was no clear effect of exercise intensity on the magnitude of post-exercise hypotension.

Heterogeneity in Clinical Practices for Post-Cardiotomy Extracorporeal Life Support: a Pilot Survey from the PELS-1 Multicenter Study.

BACKGROUND: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated the real-world PC-ECLS clinical practices. METHODS: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring and transfusions practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study. RESULTS: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patient's bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged 7-10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%) and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%) and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis. CONCLUSIONS: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of available evidence are recommended.

Development and validation of an intuitive biomechanics-based method for intraocular pressure measurement: a modal analysis approach.

BACKGROUND: Current intraocular pressure (IOP) measurements based on non-contact tonometry are derived from statistics-driven equations and lack biomechanical significance, which often leads to under-estimation in post-refractive surgery cornea. This study aims to introduce and validate modal analysis-derived intraocular pressure (mIOP) as a novel method generated through Legendre-based modal decomposition of the anterior corneal contour; it provides an accurate and intuitive IOP measurement from an energy-based perspective. METHODS: This retrospective study included 680 patients. Healthy participants were divided into reference (n = 385) and validation (n = 142) datasets, and the others underwent either femtosecond-assisted laser in situ keratomileusis (FS-LASIK, n = 58) or transepithelial photorefractive keratectomy (TPRK, n = 55). Corneal curvature of the right eyes was extracted from raw serial cross-sectional images of the cornea generated by Corvis ST, a noncontact tonometer with a high-speed Scheimpflug-camera. Legendre expansion was then applied to the corneal curvature to obtain the modal profiles (i.e., temporal changes of the coefficient for each basis polynomial [modes]). Using the reference dataset, feature selection on the modal profiles generated a final mIOP model consisting of a single parameter: total area under curve (frames 1-140) divided by the area under curve of the rising phase (frames 24-40) in the fourth mode, i.e. the M4 ratio. Validation was performed in both the healthy validation and postoperative datasets. IOP-Corvis, pachymetry-corrected IOP, biomechanically corrected IOP, and mIOP values were compared. For the FS-LASIK and TPRK groups, pairwise postoperative IOP changes were analyzed through repeated measures analysis of variance, and agreement was examined through Bland-Altman analysis. Using a finite element analysis based three-dimensional model of the human cornea, we further compared the M4 ratio with the true intraocular pressure within the physiological range. RESULTS: The M4 ratio-based mIOP demonstrated weak to negligible association with age, radius of corneal curvature, and central corneal thickness (CCT) in all validation analyses, and performed comparably with biomechanically corrected IOP (bIOP) in the refractive surgery groups. Both remained nearly constant postoperatively and were not influenced by CCT changes. Additionally, M4 ratio accurately represented true intraocular pressure in the in silico model. CONCLUSIONS: mIOP is a reliable IOP measurement in healthy and postrefractive surgery populations. This energy-based, ratio-derived approach effectively filters out pathological, rotational, misaligned movements and serves as an interpatient self-calibration index. Modal analysis of corneal deformation dynamics provides novel insights into regional corneal responses against pressure loading.

Multiple branch retinal artery occlusions following the new facial cosmetic filler (Poly-D, L-lactic Acid) injection a case report.

BACKGROUND: Poly-D, L-lactic acid is (PDLLA) a new cosmetic filler. We reported the first case of PDLLA-related devastating complication of multiple branch retinal artery occlusion (BRAO). CASE PRESENTATION: A 23-year-old female had sudden blindness after injection of PDLLA at the glabella. After emergency intraocular pressure-lowering medicine, ocular massage, steroid pulse therapy, heparin and alprostadil infusion, and subsequent treatments including acupuncture and 40 sessions of hyperbaric oxygen therapy, her best-corrected visual acuity improved from hand motion at 30 cm to 0.3 within 2 months. CONCLUSION: Although safety of PDLLA was evaluated in animal studies and in 16,000 human cases, it could still cause rare but devastating retinal artery occlusion as in the present case. Proper and immediate therapies could still improve patient's vision and scotoma. Surgeons should keep in mind the possibility of iatrogenic filler-related retinal artery occlusion.

Early predictors for maltreatment-related injuries in infancy and long-term mortality: a population-based study.

INTRODUCTION: Incidence, health consequences, and social burden associated with child maltreatment appeared to be borne disproportionately by very young children. We conducted a population-based data linkage study to explore child- and family-level factors that affect receiving different diagnoses of maltreatment injuries and investigate excessive mortality throughout toddlerhood. METHODS: We conducted a retrospective cohort study comprising 2.2 million infants born in 2004-2014 in Taiwan. Incident cases of child maltreatment were defined by hospitalization or emergency department visits for three heterogeneous diagnostic groups of maltreatment-related injuries (i.e., maltreatment syndrome, assaults, and undetermined causes) within 12 months after birth. The generalized linear model and landmark survival analyses were used to evaluate risk factors. RESULTS: An estimated 2.9‰ of infants experienced at least one maltreatment-related injury, with a three-year mortality rate of 1.3%. Low birthweight was associated with increased risk of receiving the diagnosis of three maltreatment injuries, particularly maltreatment syndrome (adjusted Incidence Rate Ratio [aIRR] = 4.08, 95% confidence interval [CI]: 2.93-5.68). Socially advantaged family condition was inversely linked with receiving the diagnosis of maltreatment syndrome and assaults (e.g., high income: aIRR = 0.55 and 0.47), yet positively linked with undetermined cause (aIRR = 2.05, 95% CI: 1.89-2.23). For infants exposed to maltreatment, low birth weight and non-attendance of postnatal care were highly predictive of fatality; low birthweight served as a vital predictor for premature death during toddlerhood (aIRR = 6.17, 95% CI: 2.36-15.4). CONCLUSIONS: Raising awareness of maltreatment-related injuries in infancy and predictors should be a priority for appropriate follow-up assessment and timely intervention.

The Role of SCL Isoforms in Embryonic Hematopoiesis.

Three waves of hematopoiesis occur in the mouse embryo. The primitive hematopoiesis appears as blood islands in the extra embryonic yolk sac at E7.5. The extra embryonic pro-definitive hematopoiesis launches in late E8 and the embryonic definitive one turns on at E10.5 indicated by the emergence of hemogenic endothelial cells on the inner wall of the extra embryonic arteries and the embryonic aorta. To study the roles of SCL protein isoforms in murine hematopoiesis, the SCL-large (SCL-L) isoform was selectively destroyed with the remaining SCL-small (SCL-S) isoform intact. It was demonstrated that SCL-S was specifically expressed in the hemogenic endothelial cells (HECs) and SCL-L was only detected in the dispersed cells after budding from HECs. The SCLΔ/Δ homozygous mutant embryos only survived to E10.5 with normal extra embryonic vessels and red blood cells. In wild-type mouse embryos, a layer of neatly aligned CD34+ and CD43+ cells appeared on the endothelial wall of the aorta of the E10.5 fetus. However, the cells at the same site expressed CD31 rather than CD34 and/or CD43 in the E10.5 SCLΔ/Δ embryo, indicating that only the endothelial lineage was developed. These results reveal that the SCL-S is sufficient to sustain the primitive hematopoiesis and SCL-L is necessary to launch the definitive hematopoiesis.