Association of Red Blood Cell Transfusion Thresholds and Outcomes in Medical Patients with Acute Respiratory Failure Supported with Extra Corporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study.

BACKGROUND: The hemoglobin value to trigger red blood cell (RBC) transfusion for patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) is controversial. Previous guidelines recommended transfusing to a normal hemoglobin, but recent studies suggest more RBC transfusions are associated with increased adverse outcomes. RESEARCH QUESTION: Is implementation of different institutional RBC transfusion thresholds for patients receiving VV-ECMO associated with changes in RBC utilization and patient outcomes? STUDY DESIGN AND METHODS: Single-center retrospective study of patients receiving VV-ECMO using segmented regression to test associations between implementation of institutional transfusion thresholds and trends in RBC utilization. Associations with secondary outcomes, including in-hospital survival, were also assessed. RESULTS: The study included 229 patients: 91 in the "no threshold (NT)" cohort, 48 in the "hemoglobin <8 g/dL (<8 g/dL)" cohort and 90 in the "hemoglobin <7 g/dL (<7 g/dL)" cohort. Despite a decrease in RBC/ECMO day following implementation of different thresholds, (mean +/- SD; 0.6 +/- 1.0 in the NT cohort, 0.3 +/- 0.8 in the <8 g/dL cohort, and 0.3 +/- 1.1 in the <7 g/dL cohort, p < 0.001), segmented regression showed no association between implementation of transfusion thresholds and changes in trends in RBC/ECMO day. We observed an increased hazard of death in the NT cohort compared to the <8 g/dL cohort (aHR: 2.08, 95% CI: 1.12-3.88), and in the <7 g/dL cohort compared to the <8g/dL cohort (aHR: 1.93, 95% CI: 1.02-3.62). There was no difference in the hazard of death between the NT and <7 g/dL cohorts (aHR: 1.08, 95% CI: 0.69-1.69). INTERPRETATION: We observed a decrease in RBC/ECMO day over time, but changes were not associated temporally with implementation of transfusion thresholds. A transfusion threshold of hemoglobin <8 g/dL was associated with a lower hazard of death, but these findings are limited by study methodology. Further research is needed investigating optimal RBC transfusion practices for patients supported with VV-ECMO.

Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice.

OBJECTIVE: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression. DESIGN: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation. RESULTS: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001). CONCLUSIONS: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability.

Mobile Application-Based Communication Facilitation Platform for Family Members of Critically Ill Patients: A Randomized Clinical Trial.

Importance: Unmet and racially disparate palliative care needs are common in intensive care unit (ICU) settings. Objective: To test the effect of a primary palliative care intervention vs usual care control both overall and by family member race. Design, Setting, and Participants: This cluster randomized clinical trial was conducted at 6 adult medical and surgical ICUs in 2 academic and community hospitals in North Carolina between April 2019 and May 2022 with physician-level randomization and sequential clusters of 2 Black patient-family member dyads and 2 White patient-family member dyads enrolled under each physician. Eligible participants included consecutive patients receiving mechanical ventilation, their family members, and their attending ICU physicians. Data analysis was conducted from June 2022 to May 2023. Intervention: A mobile application (ICUconnect) that displayed family-reported needs over time and provided ICU attending physicians with automated timeline-driven communication advice on how to address individual needs. Main Outcomes and Measures: The primary outcome was change in the family-reported Needs at the End-of-Life Screening Tool (NEST; range 0-130, with higher scores reflecting greater need) score between study days 1 and 3. Secondary outcomes included family-reported quality of communication and symptoms of depression, anxiety, and posttraumatic stress disorder at 3 months. Results: A total of 111 (51% of those approached) family members (mean [SD] age, 51 [15] years; 96 women [86%]; 15 men [14%]; 47 Black family members [42%]; 64 White family members [58%]) and 111 patients (mean [SD] age, 55 [16] years; 66 male patients [59%]; 45 Black patients [41%]; 65 White patients [59%]; 1 American Indian or Alaska Native patient [1%]) were enrolled under 37 physicians randomized to intervention (19 physicians and 55 patient-family member dyads) or control (18 physicians and 56 patient-family member dyads). Compared with control, there was greater improvement in NEST scores among intervention recipients between baseline and both day 3 (estimated mean difference, -6.6 points; 95% CI, -11.9 to -1.3 points; P = .01) and day 7 (estimated mean difference, -5.4 points; 95% CI, -10.7 to 0.0 points; P = .05). There were no treatment group differences at 3 months in psychological distress symptoms. White family members experienced a greater reduction in NEST scores compared with Black family members at day 3 (estimated mean difference, -12.5 points; 95% CI, -18.9 to -6.1 points; P < .001 vs estimated mean difference, -0.3 points; 95% CI, -9.3 to 8.8 points; P = .96) and day 7 (estimated mean difference, -9.5 points; 95% CI, -16.1 to -3.0 points; P = .005 vs estimated mean difference, -1.4 points; 95% CI, -10.7 to 7.8; P = .76). Conclusions and Relevance: In this study of ICU patients and family members, a primary palliative care intervention using a mobile application reduced unmet palliative care needs compared with usual care without an effect on psychological distress symptoms at 3 months; there was a greater intervention effect among White family members compared with Black family members. These findings suggest that a mobile application-based intervention is a promising primary palliative care intervention for ICU clinicians that directly addresses the limited supply of palliative care specialists. Trial Registration: ClinicalTrials.gov Identifier: NCT03506438.

Resistance analysis following sotrovimab treatment in participants with COVID-19 during the phase III COMET-ICE study.

Aim: Sotrovimab is an engineered human monoclonal antibody that binds a conserved region of the SARS-CoV-2 spike protein. The COMET-ICE phase III study evaluated sotrovimab for treatment of mild to moderate COVID-19 in nonhospitalized participants with ≥1 risk factor for severe disease progression. Materials & methods: We evaluated the presence of circulating SARS-CoV-2 variants of concern or interest (VOCs/VOIs) and characterized the presence of baseline, post-baseline and emergent amino acid substitutions detected in the epitope of sotrovimab in SARS-CoV-2. Results: None of the sotrovimab-treated participants with baseline epitope substitutions, and 1 of 48 sotrovimab-treated participants with post-baseline epitope substitutions, met the primary clinical endpoint for progression. Conclusion: Overall, progression was not associated with identified VOC/VOI or the presence of epitope substitutions in sotrovimab-treated participants.

Analysis of the genetics of the SARS-CoV-2 virus from participants in a clinical study for treatment of COVID-19 In a large clinical study, the ability of the monoclonal antibody sotrovimab to treat patients with mild to moderate COVID-19 was looked at. This paper focuses on the genetics of the SARS-CoV-2 viruses from participants in this clinical study. Overall, most participants in the study were infected with the original 'wild type' variant of SARS-CoV-2. We also looked for changes in the virus at the positions on the viral spike protein where sotrovimab binds. In participants treated with sotrovimab, changes in the virus at the site where sotrovimab binds on the viral surface protein were not associated with negative outcomes in participants. Clinical Trial Registration: NCT04545060 (ClinicalTrials.gov).

Ability of the respiratory ECMO survival prediction (RESP) score to predict survival for patients with COVID-19 ARDS and non-COVID-19 ARDS: a single-center retrospective study.

The respiratory ECMO survival prediction (RESP) score is used to predict survival for patients managed with extracorporeal membrane oxygenation (ECMO), but its performance in patients with Coronavirus Disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is unclear. We evaluated the ability of the RESP score to predict survival for patients with both non-COVID 19 ARDS and COVID-19 ARDS managed with ECMO at our institution. Receiver operating characteristic area under the curve (AUC) analysis found the RESP score reasonably predicted survival in patients with non-COVID-19 ARDS (AUC 0.76, 95% CI 0.68-0.83), but not patients with COVID-19 ARDS (AUC 0.54, 95% CI 0.41-0.66).

Assessment of symptoms in COMET-ICE, a phase 2/3 study of sotrovimab for early treatment of non-hospitalized patients with COVID-19.

BACKGROUND: The COMET-ICE trial demonstrated that sotrovimab clinically and statistically significantly reduces the risk of all-cause > 24-h hospitalization or death due to any cause among patients with COVID-19 at high risk of disease progression. Patient-reported outcomes are important to capture symptom burden of COVID-19 and assess treatment effectiveness. This study investigated symptoms and their impact over the acute phase of COVID-19 infection among patients on sotrovimab versus placebo. METHODS: Randomized (1:1), double-blind, multicenter, placebo-controlled, phase 2/3 study in 57 centers across five countries. Participants were non-hospitalized patients with symptomatic, mild-to-moderate COVID-19 and ≥ 1 baseline risk factor for disease progression (aged ≥ 55 years or ≥ 1 of the following: diabetes requiring medication, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate-to-severe asthma). An intravenous infusion of sotrovimab 500 mg or placebo was administered on Day 1. The FLU-PRO Plus questionnaire was administered once-daily with 24-h recall from Day 1-21, and at Day 29. Intensity and duration of COVID-19 symptoms were determined from area under the curve (AUC) and mean change in total and individual domain scores through Days 7, 14, and 21. Time to symptom alleviation was assessed. RESULTS: In total, 1057 patients were randomized to sotrovimab (n = 528) or placebo (n = 529). At Day 7, mean decrease in FLU-PRO Plus total score (measured by AUC) was statistically significantly greater for patients on sotrovimab (-3.05 [95% confidence interval (CI) -3.27 to -2.83]) than placebo (-1.98 [95% CI -2.20 to -1.76]; difference -1.07 [95% CI -1.38 to -0.76]; p < 0.001). Significant differences were also observed at Days 14 and 21. A more rapid decline in symptom severity was observed with sotrovimab versus placebo through Week 1 and the first 21 days post-treatment. By Day 21, 41% of patients on sotrovimab and 34% on placebo reported symptom resolution. In a post-hoc analysis, median time to symptom alleviation was 4 and 6 days, respectively. CONCLUSIONS: Sotrovimab provides significant and rapid improvements in patient-reported COVID-19 symptoms, as measured by the FLU-PRO Plus. These results further show the benefits of sotrovimab in alleviating symptoms among high-risk patients with COVID-19. Trial registration ClinicalTrials.Gov: NCT04545060 ( https://clinicaltrials.gov/ct2/show/NCT04545060 ). Date of registration: September 10, 2020 (retrospectively registered).

Response of cells and tissues to shear stress.

Shear stress is essential for normal physiology and malignancy. Common physiological processes - such as blood flow, particle flow in the gut, or contact between migratory cell clusters and their substrate - produce shear stress that can have an impact on the behavior of different tissues. In addition, shear stress has roles in processes of biomedical interest, such as wound healing, cancer and fibrosis induced by soft implants. Thus, understanding how cells react and adapt to shear stress is important. In this Review, we discuss in vivo and in vitro data obtained from vascular and epithelial models; highlight the insights these have afforded regarding the general mechanisms through which cells sense, transduce and respond to shear stress at the cellular levels; and outline how the changes cells experience in response to shear stress impact tissue organization. Finally, we discuss the role of shear stress in collective cell migration, which is only starting to be appreciated. We review our current understanding of the effects of shear stress in the context of embryo development, cancer and fibrosis, and invite the scientific community to further investigate the role of shear stress in these scenarios.

Paracrine regulation of neural crest EMT by placodal MMP28.

Epithelial-mesenchymal transition (EMT) is an early event in cell dissemination from epithelial tissues. EMT endows cells with migratory, and sometimes invasive, capabilities and is thus a key process in embryo morphogenesis and cancer progression. So far, matrix metalloproteinases (MMPs) have not been considered as key players in EMT but rather studied for their role in matrix remodelling in later events such as cell migration per se. Here, we used Xenopus neural crest cells to assess the role of MMP28 in EMT and migration in vivo. We show that a catalytically active MMP28, expressed by neighbouring placodal cells, is required for neural crest EMT and cell migration. We provide strong evidence indicating that MMP28 is imported in the nucleus of neural crest cells where it is required for normal Twist expression. Our data demonstrate that MMP28 can act as an upstream regulator of EMT in vivo raising the possibility that other MMPs might have similar early roles in various EMT-related contexts such as cancer, fibrosis, and wound healing.

Validation of a Low-Cost Portable Device for Inducing Noninvasive Anterior Cruciate Ligament Injury in Mice.

Noninvasive compression-induced anterior cruciate ligament rupture (ACL-R) is an easy and reproducible model for studying post-traumatic osteoarthritis (PTOA) in mice. However, equipment typically used for ACL-R is expensive, immobile, and not available to all researchers. In this study, we compared PTOA progression in mice injured with a low-cost custom ACL-rupture device (CARD) to mice injured with a standard system (ElectroForce 3200). We quantified anterior-posterior (AP) joint laxity immediately following injury, epiphyseal trabecular bone microstructure, and osteophyte volume at 2 and 6 weeks post injury using micro-computed tomography, and osteoarthritis progression and synovitis at 2 and 6 weeks post injury using whole-joint histology. We observed no significant differences in outcomes in mice injured with the CARD system compared to mice injured with the Electroforce (ELF) system. However, AP joint laxity data and week 2 micro-CT and histology outcomes suggested that injuries may have been slightly more severe and PTOA progressed slightly faster in mice injured with the CARD system compared to the ELF system. Altogether, these data confirm that ACL-R can be successfully and reproducibly performed with the CARD system and that osteoarthritis (OA) progression is mostly comparable to that of mice injured with the ELF system, though potentially slightly faster. The CARD system is low cost and portable, and we are making the plans and instructions freely available to all interested investigators in the hopes that they will find this system useful for their studies of OA in mice.

Mobile Mindfulness for Psychological Distress and Burnout among Frontline COVID-19 Nurses: A Pilot Randomized Trial.

Rationale: The coronavirus disease (COVID-19) pandemic exacerbated psychological distress and burnout in frontline healthcare workers. Interventions addressing psychological distress and burnout among these workers are lacking. Objectives: To determine the feasibility and explore the impact of mobile mindfulness to treat psychological distress and burnout among nurses in frontline COVID-19 units. Methods: We conducted a pilot randomized trial of 102 nurses working in COVID-19 units at a single hospital between May 2021 and January 2022. Participants were randomized to mobile mindfulness (intervention) or waiting list (control). The primary outcome was feasibility, assessed by comparing rates of randomization, retention, and intervention completion to predefined targets. Secondary outcomes were changes in psychological distress (Patient Health Questionnaire-9, General Anxiety Disorder-7, Perceived Stress Scale-4) and burnout symptoms (Maslach Burnout Inventory) after 1 month. Results: We randomized 102 of 113 consented individuals (90%, target 80%), and 88 completed follow-up (86%, target 80%). Among 69 intervention participants, 19 completed ⩾1 mindfulness session per week (28%, target 60%), and 13 completed ⩾75% of mindfulness sessions (19%, target 50%). Intervention participants had greater decreases in Patient Health Questionnaire-9 scores than control subjects (difference in differences, -2.21; 95% confidence interval, -3.99, -0.42; P = 0.016), but the Maslach Burnout Inventory depersonalization scores decreased more in the control arm than in the intervention arm (difference in differences, 1.60; 95% confidence interval, 0.18, 3.02; P = 0.027). There were no other changes in emotional distress or burnout symptoms. Conclusions: This trial of mobile mindfulness in frontline nurses met feasibility targets for randomization and retention, but participants had modest intervention use. Intervention participants had a reduction in depression symptoms, but not in burnout. Clinical trial registered with www.clinicaltrials.gov (NCT04816708).

Monitoring river turbidity after a mine tailing dam failure using an empirical model derived from Sentinel-2 imagery.

Sudden failure of a mine tailing dam occurred in the municipality of Brumadinho, Minas Gerais, Brazil, on January 25, 2019. Approximately 12 million cubic meters of mine tailings discharged into the Paraopeba River, producing strong environmental and societal impacts, mainly due to a massive increase in turbidity (occasionally exceeding 50,000 Nephelometric Turbidity Units [NTU] (CPRM 2019). Remote sensing is a well-established tool for quantifying spatial patterns of turbidity. However, a few empirical models have been developed to map turbidity in rivers impacted by mine tailings. Thus, this study aimed to develop an empirical model capable of producing turbidity estimates based on images from the Sentinel-2 satellite, using the Paraopeba River as the study area. We found that river turbidity was most strongly correlated with the sensor's near-infrared band (NIR) (band 8). Thus, we built an empirical single-band model using an exponential function with an (R2 of 0.91) to characterize the spatial-temporal variation of turbidity based on satellite observations of NIR reflectance. Although the role of discharged tailings in the seasonal variation of turbidity is not well understood, the proposed model enabled the monitoring of turbidity variations in the Paraopeba River associated with seasonal resuspension or deposition of mine tailings. Our study shows the capability of single-band models to quantify seasonal variations in turbidity in rivers impacted by mine tailing pollution.

Tissue interplay during morphogenesis.

The process by which biological systems such as cells, tissues and organisms acquire shape has been named as morphogenesis and it is central to a plethora of biological contexts including embryo development, wound healing, or even cancer. Morphogenesis relies in both self-organising properties of the system and in environmental inputs (biochemical and biophysical). The classical view of morphogenesis is based on the study of external biochemical molecules, such as morphogens. However, recent studies are establishing that the mechanical environment is also used by cells to communicate within tissues, suggesting that this mechanical crosstalk is essential to synchronise morphogenetic transitions and self-organisation. In this article we discuss how tissue interaction drive robust morphogenesis, starting from a classical biochemical view, to finalise with more recent advances on how the biophysical properties of a tissue feedback with their surroundings to allow form acquisition. We also comment on how in silico models aid to integrate and predict changes in cell and tissue behaviour. Finally, considering recent advances from the developmental biomechanics field showing that mechanical inputs work as cues that promote morphogenesis, we invite to revisit the concept of morphogen.

Biopolymer Non-Parametric Analysis: A Degradation Study under Accelerated Destructive Tests.

The degradation of biopolymers such as polylactic acid (PLA) has been studied for several years; however, the results regarding the mechanism of degradation are not completely understood yet. PLA is easily processed by traditional techniques including injection molding, blow molding, extrusion, and thermoforming; in this research, the extrusion and injection molding processes were used to produce PLA samples for accelerated destructive testing. The methodology employed consisted of carrying out material testing under the guidelines of several ASTM standards; this research hypothesized that the effects of UV light, humidity, and temperature exposure have a statistical difference in the PLA degradation rate. The multivariate analysis of non-parametric data is presented as an alternative to multivariate analysis, in which the data do not satisfy the essential assumptions of a regular MANOVA, such as multivariate normality. A package in the R software that allows the user to perform a non-parametric multivariate analysis when necessary was used. This paper presents a study to determine if there is a significant difference in the degradation rate after 2000 h of accelerated degradation of a biopolymer using the multivariate and non-parametric analyses of variance. The combination of the statistical techniques, multivariate analysis of variance and repeated measures, provided information for a better understanding of the degradation path of the biopolymer.

Identification of novel neutralizing determinants for protection against HCV.

BACKGROUND AND AIMS: HCV evasion of neutralizing antibodies (nAb) results in viral persistence and poses challenges to the development of an urgently needed vaccine. N-linked glycosylation of viral envelope proteins is a key mechanism for such evasion. To facilitate rational vaccine design, we aimed to identify determinants of protection of conserved neutralizing epitopes. APPROACH AND RESULTS: Using a reverse evolutionary approach, we passaged genotype 1a, 1b, 2a, 3a, and 4a HCV with envelope proteins (E1 and E2) derived from chronically infected patients without selective pressure by nAb in cell culture. Compared with the original viruses, HCV recombinants, engineered to harbor substitutions identified in polyclonal cell culture-passaged viruses, showed highly increased fitness and exposure of conserved neutralizing epitopes in antigenic regions 3 and 4, associated with protection from chronic infection. Further reverse genetic studies of acquired E1/E2 substitutions identified positions 418 and 532 in the N1 and N6 glycosylation motifs, localizing to adjacent E2 areas, as key regulators of changes of the E1/E2 conformational state, which governed viral sensitivity to nAb. These effects were independent of predicted glycan occupancy. CONCLUSIONS: We show how N-linked glycosylation motifs can trigger dramatic changes in HCV sensitivity to nAb, independent of glycan occupancy. These findings aid in the understanding of HCV nAb evasion and rational vaccine design, as they can be exploited to stabilize the structurally flexible envelope proteins in an open conformation, exposing important neutralizing epitopes. Finally, this work resulted in a panel of highly fit cell culture infectious HCV recombinants.

Trajectories of Palliative Care Needs in the ICU and Long-Term Psychological Distress Symptoms.

OBJECTIVES: While palliative care needs are assumed to improve during ICU care, few empiric data exist on need trajectories or their impact on long-term outcomes. We aimed to describe trajectories of palliative care needs during ICU care and to determine if changes in needs over 1 week was associated with similar changes in psychological distress symptoms at 3 months. DESIGN: Prospective cohort study. SETTING: Six adult medical and surgical ICUs. PARTICIPANTS: Patients receiving mechanical ventilation for greater than or equal to 2 days and their family members. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the 13-item Needs at the End-of-Life Screening Tool (NEST; total score range 0-130) completed by family members at baseline, 3, and 7 days. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Post-Traumatic Stress Scale (PTSS) were completed at baseline and 3 months. General linear models were used to estimate differences in distress symptoms by change in need (NEST improvement ≥ 10 points or not). One-hundred fifty-nine family members participated (median age, 54.0 yr [interquartile range (IQR), 44.0-63.0 yr], 125 [78.6%] female, 54 [34.0%] African American). At 7 days, 53 (33%) a serious level of overall need and 35 (22%) ranked greater than or equal to 1 individual need at the highest severity level. NEST scores improved greater than or equal to 10 points in only 47 (30%). Median NEST scores were 22 (IQR, 12-40) at baseline and 19 (IQR, 9-37) at 7 days (change, -2.0; IQR, -11.0 to 5.0; p = 0.12). There were no differences in PHQ-9, GAD-7, or PTSS change scores by change in NEST score (all p > 0.15). CONCLUSIONS: Serious palliative care needs were common and persistent among families during ICU care. Improvement in needs was not associated with less psychological distress at 3 months. Serious needs may be commonly underrecognized in current practice.

Malpractice Cases Arising From Telephone Based Telemedicine Triage in Ophthalmology.

PURPOSE: To determine the allegation, precipitating medical issue, and outcome of telephone triage focused malpractice litigation among ophthalmologists. METHODS: The WestLaw Edge database was reviewed using terms pertaining to ophthalmology and telemedicine. The search ranged from 4/7/30 to 1/25/22. RESULTS: Of the 510 lawsuits, 3.5% (18/510) met inclusion criteria. 94.5% (17/18) alleged delays in evaluation and/or treatment. 61.1% (11/18) alleged incorrect diagnoses, 38.9% (7/18) claimed improper discussion of risks or informed consent, and 5.6% (1/18) alleged delayed referrals. The precipitating medical issues included retinal detachment in 33.3% (6/18) of cases, post-procedure and post-trauma endophthalmitis in 33.3% (6/18) of cases, ocular trauma without endophthalmitis in 22.2% (4/18) of cases, and bilateral acute retinal necrosis and allergic reactions each accounting for 5.6% (1/18) of cases. CONCLUSION: Telephone triage creates potential malpractice litigation. Delay in in-person clinical evaluation and alleged failure to inform patients of possible irreversible vision loss may lead to potential malpractice litigation. We suggest offering the option of same day in person evaluation and informing the patient how delay may lead to irreversible vision loss.

RanBP1 plays an essential role in directed migration of neural crest cells during development.

Collective cell migration is essential for embryonic development, tissue regeneration and repair, and has been implicated in pathological conditions such as cancer metastasis. It is, in part, directed by external cues that promote front-to-rear polarity in individual cells. However, our understanding of the pathways that underpin the directional movement of cells in response to external cues remains incomplete. To examine this issue we made use of neural crest cells (NC), which migrate as a collective during development to generate vital structures including bones and cartilage. Using a candidate approach, we found an essential role for Ran-binding protein 1 (RanBP1), a key effector of the nucleocytoplasmic transport pathway, in enabling directed migration of these cells. Our results indicate that RanBP1 is required for establishing front-to-rear polarity, so that NCs are able to chemotax. Moreover, our work suggests that RanBP1 function in chemotaxis involves the polarity kinase LKB1/PAR4. We envisage that regulated nuclear export of LKB1 through Ran/RanBP1 is a key regulatory step required for establishing front-to-rear polarity and thus chemotaxis, during NC collective migration.

An Update and Report Failure of Surgical Syndactyly Repair in Harlequin Ichthyosis.

Harlequin ichthyosis (HI) is a rare congenital skin disorder caused by irregular epidermal differentiation. Syndactyly in HI is associated with thick hyperkeratotic skin flexion and angulation deformity of the hand and fingers resulting in limited function of the upper extremity. Traditional syndactyly release is limited as full-thickness skin grafts typically used in reconstruction are composed of diseased skin and require donor sites in a patient predisposed for adverse wound healing. This case report is a follow-up to a previous viewpoint written about digital escharotomies in a newborn with HI and outlines a second and fourth webspace syndactyly release with a dermal substitute. Despite early evidence of adequate release and improved hand function, recurrence of syndactyly was observed within 4 months of surgical release. Our experience described within this case report may suggest the limitations and possible alternatives of surgical release of syndactyly in the HI population.