Scalp hypothermia to reduce chemotherapy-induced alopecia: A systematic review and meta-analysis.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a common and emotionally-taxing side effect of chemotherapy, including taxane agents used frequently in treatment of gynecologic cancers. Scalp hypothermia, also known as "cold caps", is a possible method to prevent severe CIA, studied primarily in the breast cancer population. OBJECTIVES: To compile existing data on scalp hypothermia in cancer patients receiving taxane chemotherapy in order to investigate its application to the gynecologic cancer population. SEARCH STRATEGY: MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and Cochrane were searched through January 31, 2023. SELECTION CRITERIA: Full-text manuscripts reporting on the results of scalp hypothermia in patients receiving taxane-based chemotherapy. DATA COLLECTION AND ANALYSIS: Binomial proportions were summed, and random-effects meta-analyses performed. MAIN RESULTS: From 1424 records, we included 31 studies, representing 14 different countries. Only 5 studies included gynecologic cancer patients. We extracted the outcome of the proportion of patients with <50% hair loss. Among 2179 included patients, 60.7% were reported to have <50% hair loss (meta-analysis: 60.6%, 95% confidence interval [CI] 54.9-66.1%). Among the 28 studies reporting only on taxane-based chemotherapy, the rate of <50% hair loss was 60.0% (meta-analysis: 60.9%, (95% CI: 54.9-66.7%). In comparative studies, hair loss was significantly less in patients who received scalp hypothermia versus those who did not (49.3% versus 0% with <50% hair loss; OR 40.3, 95% CI: 10.5-154.8). Scalp cooling achieved <50% hair loss in patients receiving paclitaxel (67.7%; meta-analysis 69.9%, 95% CI 64.1-75.4%) and docetaxel (57.1%; meta-analysis 60.5%, 95% CI 50.0-71.6%). Meta-analysis on patient satisfaction in regard to scalp cooling found a satisfaction rate of 78.9% (95% CI 69.1-87.4%). CONCLUSION: Scalp hypothermia may be an effective method to reduce some cases of CIA due to taxane chemotherapy, especially paclitaxel. More trials need to be done to determine the precise effects of scalp hypothermia in gynecologic cancer patients.

Therapeutic Modulation of Arginase with nor-NOHA Alters Immune Responses in Experimental Mouse Models of Pulmonary Tuberculosis including in the Setting of Human Immunodeficiency Virus (HIV) Co-Infection.

L-arginine metabolism is strongly linked with immunity to mycobacteria, primarily through the antimicrobial activity of nitric oxide (NO). The potential to modulate tuberculosis (TB) outcomes through interventions that target L-arginine pathways are limited by an incomplete understanding of mechanisms and inadequate in vivo modeling. These gaps in knowledge are compounded for HIV and Mtb co-infections, where activation of arginase-1 due to HIV infection may promote survival and replication of both Mtb and HIV. We utilized in vitro and in vivo systems to determine how arginase inhibition using Nω-hydroxy-nor-L-arginine (nor-NOHA) alters L-arginine pathway metabolism relative to immune responses and disease outcomes following Mtb infection. Treatment with nor-NOHA polarized murine macrophages (RAW 264.7) towards M1 phenotype, increased NO, and reduced Mtb in RAW macrophages. In Balb/c mice, nor-NOHA reduced pulmonary arginase and increased the antimicrobial metabolite spermine in association with a trend towards reduced Mtb CFU in lung. In humanized immune system (HIS) mice, HIV infection increased plasma arginase and heightened the pulmonary arginase response to Mtb. Treatment with nor-NOHA increased cytokine responses to Mtb and Mtb/HIV in lung tissue but did not significantly alter bacterial burden or viral load. Our results suggest that L-arginine pathway modulators may have potential as host-directed therapies to augment antibiotics in TB chemotherapy.

Vaulting further: cranial vault expansion for craniocerebral disproportion without primary craniosynostosis.

PURPOSE: Treatment of subjects with refractory idiopathic intracranial hypertension (IIH) or shunted hydrocephalus with chronic shunt complications is challenging. What is the role for cranial vault expansion, particularly utilizing posterior vault distraction osteogenesis (PVDO), in these cases? This study assesses medium-term efficacy of cranial vault expansion in this unique patient population. METHODS: A retrospective review was conducted of patients who underwent cranial vault expansion from 2008 to 2023 at the Children's Hospital of Philadelphia. Subjects who did not have a diagnosis of primary craniosynostosis were included in the study. Demographic information, medical history, and perioperative details were collected from medical records. Primary outcomes were the rate of CSF diversion procedures and resolution of presenting signs and symptoms. Secondary outcomes were perioperative and 90-day complications and reoperation requirement. RESULTS: Among 13 included subjects, nine (69.2%) patients had a primary diagnosis of shunted hydrocephalus and 4 (30.8%) patients had IIH. Twelve (92.3%) subjects underwent posterior vault distraction osteogenesis (PVDO) and one (7.7%) underwent posterior vault remodeling (PVR). All 4 patients with IIH demonstrated symptomatic improvement following PVDO, including resolution of headaches, vomiting, and/or papilledema. Among 9 patients with shunted hydrocephalus, CSF diversion requirement decreased from 2.7 ± 1.6 procedures per year preoperatively to 1.2 ± 1.8 per year following cranial vault expansion (p = 0.030). The mean postoperative follow-up was 4.1 ± 2.1 years and four (30.8%) patients experienced complications within 90 days of surgery, including infection (n = 2), CSF leak (n = 1), and elevated ICP requiring lumbar puncture (n = 1). Four (30.8%) patients underwent repeat cranial vault expansion for recurrence of ICP-related symptoms. At most recent follow-up, 7 of 9 patients with shunted hydrocephalus demonstrated symptomatic improvement. CONCLUSION: Cranial vault expansion reduced intracranial hypertension-related symptomology as well as the rate of CSF diversion-related procedures in patients with refractory IIH and shunted hydrocephalus without craniosynostosis, and should be considered in those who have significant shunt morbidity.

Lattice ultrasensitivity produces large gain in E. coli chemosensing.

E. coli use a regular lattice of receptors and attached kinases to detect and amplify faint chemical signals. Kinase output is characterized by precise adaptation to a wide range of background ligand levels and large gain in response to small relative changes in ligand concentration. These characteristics are well described by models which achieve their gain through equilibrium cooperativity. But these models are challenged by two experimental results. First, neither adaptation nor large gain are present in receptor binding assays. Second, in cells lacking adaptation machinery, fluctuations can sometimes be enormous, with essentially all kinases transitioning together. Here we introduce a far-from equilibrium model in which receptors gate the spread of activity between neighboring kinases. This model achieves large gain through a mechanism we term lattice ultrasensitivity (LU). In our LU model, kinase and receptor states are separate degrees of freedom, and kinase kinetics are dominated by chemical rates far-from-equilibrium rather than by equilibrium allostery. The model recapitulates the successes of past models, but also matches the challenging experimental findings. Importantly, unlike past lattice critical models, our LU model does not require parameters to be fine tuned for function.

Lattice ultrasensitivity produces large gain in E. coli chemosensing.

E. coli use a regular lattice of receptors and attached kinases to detect and amplify faint chemical signals. Kinase output is characterized by precise adaptation to a wide range of background ligand levels and large gain in response to small relative changes in ligand concentration. These characteristics are well described by models which achieve their gain through equilibrium cooperativity. But these models are challenged by two experimental results. First, neither adaptation nor large gain are present in receptor binding assays. Second, in cells lacking adaptation machinery, fluctuations can sometimes be enormous, with essentially all kinases transitioning together. Here we introduce a far-from equilibrium model in which receptors gate the spread of activity between neighboring kinases. This model achieves large gain through a mechanism we term lattice ultrasensitivity (LU). In our LU model, kinase and receptor states are separate degrees of freedom, and kinase kinetics are dominated by chemical rates far-from-equilibrium rather than by equilibrium allostery. The model recapitulates the successes of past models, but also matches the challenging experimental findings. Importantly, unlike past lattice critical models, our LU model does not require parameters to be fine tuned for function.

Columbia-Suicide Severity Rating Scale (C-SSRS) Reveals High Rates of Suicidality in 602 Patients With Cleft and Craniofacial Conditions.

INTRODUCTION: Little is known about rates of suicidal ideation and behavior among youth with cleft lip and/or palate (CLP) and other craniofacial conditions. METHODS: Records of patients ages 6 and older who were administered the Columbia-Suicide Severity Rating Scale (C-SSRS) Lifetime Version during routine multidisciplinary cleft or craniofacial team visits between 2019 and 2023 were examined. Demographics information, C-SSRS data, and diagnoses were assessed with statistics including t tests, the Fisher exact test, and odds ratios. RESULTS: A total of 1140 C-SSRS questionnaires across 602 (433 CLP and 169 craniofacial) patients with an average age of 11.2±3.7 years were included. Eighty-four (13.6%) patients endorsed lifetime suicidal ideation, 9 (1.5%) had at least one instance of suicidal behavior, 30 (5.0%) endorsed nonsuicidal self-injury, and 2 (0.3%) engaged in self-injurious behavior. Compared with CLP, those with other craniofacial conditions had similar odds of endorsing suicidal ideation and behavior (P≥0.05). Compared with those with isolated cleft palates, CLP had greater odds of endorsing suicidal ideation and behavior, though those differences were not significant (P≥0.05). Incidence of suicidality was unchanged before, during, and after the COVID-19 pandemic (P≥0.05). Dividing patients by sex or insurance type revealed no difference in suicidality (P≥0.05). CONCLUSION: Patients with CLP and craniofacial conditions have a high incidence of suicidal ideation and behavior, though levels are similar between these groups. Suicidality in these patients was not negatively impacted by the COVID-19 pandemic. Early identification of safety risks and psychosocial challenges through regular screening can facilitate connection with appropriate clinical interventions.

Enhanced osteochondral repair by leukocyte-depleted platelet-rich plasma in combination with adipose-derived mesenchymal stromal cells encapsulated in a three-dimensional photocrosslinked injectable hydrogel in a rabbit model.

INTRODUCTION: Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model. METHODS: Thirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume. RESULTS: In terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect. CONCLUSION: Regeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.

Early posterior vault distraction osteogenesis changes the syndromic craniosynostosis treatment paradigm: long-term outcomes of a 23-year cohort study.

BACKGROUND: Early surgical management of syndromic craniosynostosis varies widely between centers, with patients typically undergoing multiple intracranial procedures through childhood. This study evaluates the long-term impact of early posterior vault distraction osteogenesis (PVDO) versus conventional treatment paradigms on the number and timing of subsequent craniofacial procedures. METHODS: We retrospectively analyzed the longitudinal operative patterns of patients with syndromic craniosynostosis treated from 2000 to 2023 with greater than five years of follow-up. Outcomes of patients who underwent early PVDO and conventional vault reconstruction were compared. RESULTS: Fifty-five patients met the inclusion criteria (30 PVDO and 25 conventional). Age at initial vault surgery was similar between the PVDO and conventional cohorts (7.6 vs. 8.8 months), as were baseline craniometrics (p > 0.05). Multiple fronto-orbital advancement (FOA) procedures were performed in only 1/30 (3%) PVDO-treated patient versus 12/25 (48%) conventionally-treated patients (p < 0.001). Twelve (40%) PVDO-treated patients did not undergo FOA at all. Among patients with Apert and Crouzon syndromes, fewer PVDO-treated patients required FOA prior to midface surgery (33% vs. 92%, p = 0.004) or repeat FOA (6% vs. 50%, p = 0.005) compared to conventionally-treated patients. Among patients with Muenke and Saethre-Chotzen syndromes, a similar proportion of patients required FOA in the PVDO and conventional cohorts (91% vs. 100%, p = 0.353), though no PVDO-treated patients required repeat FOA (0% vs. 44%, p = 0.018). CONCLUSIONS: Early PVDO is associated with a reduction in the high burden of both FOA and, critically, revisionary frontal procedures which are commonly seen in conventionally-treated patients with syndromic craniosynostosis.

Management of the peri-intubation period in patients with pulmonary arterial hypertension and respiratory failure.

PURPOSE OF REVIEW: The endotracheal intubation of patients with pulmonary arterial hypertension (PAH) in respiratory distress is a highly morbid procedure that can precipitate hemodynamic collapse. Here we review our strategy for confronting this difficult clinical situation. RECENT FINDINGS: There are no clinical trials that explore best practices in the management of patients with PAH and respiratory failure. Here we provide a practical approach to respiratory support, inopressor and pulmonary vasodilator selection, hemodynamic considerations, point-of-care ultrasound monitoring, and endotracheal intubation in patients with PAH in respiratory failure.

The Expanded Forehead Flap for Resurfacing of Multi-unit Congenital Nevi of the Face.

The forehead flap is a timeless and robust reconstructive option for complex facial defects. In accordance with aesthetic subunit principles, it has traditionally been used to resurface defects affecting a single cervicofacial region, most commonly the nose or periorbital unit. In this article, we present three cases of congenital nevi treated with expanded forehead flap reconstruction of the nasal, periorbital, and cheek units in early childhood. This series demonstrates an approach that, while violating facial units, limits total scar burden and optimizes aesthetic and functional results. With precise staging and execution, this reconstructive technique allows for a single flap to resurface multi-unit defects in the pediatric population with excellent long-term results.

Periorbital Outcomes and Vision Risk Stratification in Treacher Collins Syndrome.

BACKGROUND: We examined ophthalmologic outcomes and periorbital management in patients with Treacher Collins syndrome (TCS). METHODS: A retrospective cohort study was performed of children with TCS treated from 2009 to 2023 at our center. Demographics and medical history were collected. Primary outcomes were periorbital findings, surgical burden, and visual acuity. Patients were stratified by risk of vision loss based on ophthalmologic findings. RESULTS: Among 50 subjects, mean follow-up was 10.5±5.9 years. Periorbital findings included downslanting palpebral fissures (100%), eyelash deficiency (70%), eyelid coloboma (54%), and significant refractive error (50%). Twenty (40%) individuals underwent 86 periorbital procedures, including lateral canthopexy (n=23 operations) and malar/zygomatic reconstruction/augmentation (n=20). Lateral canthopexies accompanied by malar fat grafting were less likely to require reoperation (0% versus 72%, p=0.004). Subjects with eyelid coloboma were more likely to have exposure keratopathy (30% versus 4%, p=0.020). Grouped by risk of vision loss, 58% were "High" risk, 18% were "Moderate", and 24% were "Low". Among 78 eyes of 39 subjects, vision was "Good" in 90%, "Fair" in 5%, and "Poor" in 6%. Vision risk grading was associated with visual acuity outcomes (n=29) (p=0.050). CONCLUSIONS: In assessing long-term ophthalmological outcomes, we noted good vision despite significant periorbital anomalies. Though most eyelid colobomas can be managed with lubrication, those threatening corneal integrity should be repaired in infancy. As timely intervention may prevent visual impairment, we recommend perinatal ophthalmologist evaluation for all children with TCS. Our proposed vision risk scale may serve as a helpful paradigm by which to contemplate vision-related issues.

Lower Prevalence of Asymptomatic Alzheimer's Disease Among Healthy African Americans.

OBJECTIVE: Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date examining cerebrospinal fluid AD biomarkers in AA individuals. METHODS: We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non-AD cases, including 495 (16.5%) self-identified black/AA and 2,456 (81.7%) white/European individuals using cutoffs derived from the Alzheimer's Disease Neuroimaging Initiative, and using a data-driven multivariate Gaussian mixture of regressions. RESULTS: Distinct effects of race were found in different groups. Total Tauand phospho181-Tau were lower among AA individuals in all groups (p < 0.0001), and Aß42 was markedly lower in AA controls compared with white controls (p < 0.0001). Gaussian mixture of regressions modeling of cerebrospinal fluid distributions incorporating adjustments for covariates revealed coefficient estimates for AA race comparable with 2-decade change in age. Using Alzheimer's Disease Neuroimaging Initiative cutoffs, fewer AA controls were classified as biomarker-positive asymptomatic AD (8.0% vs 13.4%). After adjusting for covariates, our Gaussian mixture of regressions model reduced this difference, but continued to predict lower prevalence of asymptomatic AD among AA controls (9.3% vs 13.5%). INTERPRETATION: Although the risk of dementia is higher, data-driven modeling indicates lower frequency of asymptomatic AD in AA controls, suggesting that dementia among AA populations may not be driven by higher rates of AD. ANN NEUROL 2024.

Endogenous opioids facilitate stress-induced binge eating via an insular cortex-claustrum pathway.

Stress has been shown to promote the development and persistence of binge eating behaviors. However, the neural circuit mechanisms for stress-induced binge-eating behaviors are largely unreported. The endogenous dynorphin (dyn)/kappa opioid receptor (KOR) opioid neuropeptide system has been well-established to be a crucial mediator of the anhedonic component of stress. Here, we aimed to dissect the basis of dynorphinergic control of stress-induced binge-like eating behavior. We first established a mouse behavioral model for stress-induced binge-like eating behaviors. We found that mice exposed to stress increased their food intake of familiar palatable food (high fat, high sugar, HPD) compared to non-stressed mice. Following a brain-wide analysis, we isolated robust cFos-positive cells in the Claustrum (CLA), a subcortical structure with highly abundant KOR expression, following stress-induced binge-eating behavior. We report that KOR signaling in CLA is necessary for this elevated stress-induced binge eating behavior using local pharmacology and local deletion of KOR. In vivo calcium recordings using fiber photometry revealed a disinhibition circuit structure in the CLA during the initiation of HPD feeding bouts. We further established the dynamics of endogenous dynorphinergic control of this behavior using a genetically encoded dynorphin biosensor, Klight. Combined with 1-photon single-cell calcium imaging, we report significant heterogeneity with the CLA population during stress-induced binge eating and such behavior attenuates local dynorphin tone. Furthermore, we isolate the anterior Insular cortex (aIC) as the potential source of endogenous dynorphin afferents in the CLA. By characterizing neural circuits and peptidergic mechanisms within the CLA, we uncover a pathway that implicates endogenous opioid regulation stress-induced binge eating.

Sex Differences in Characteristics, Resource Utilization, and Outcomes of Cardiogenic Shock: Data From the Critical Care Cardiology Trials Network (CCCTN) Registry.

BACKGROUND: Sex disparities exist in the management and outcomes of various cardiovascular diseases. However, little is known about sex differences in cardiogenic shock (CS). We sought to assess sex-related differences in the characteristics, resource utilization, and outcomes of patients with CS. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of advanced cardiac intensive care units (CICUs) in North America. Between 2018 and 2022, each center (N=35) contributed annual 2-month snapshots of consecutive CICU admissions. Patients with CS were stratified as either CS after acute myocardial infarction or heart failure-related CS (HF-CS). Multivariable logistic regression was used for analyses. RESULTS: Of the 22 869 admissions in the overall population, 4505 (20%) had CS. Among 3923 patients with CS due to ventricular failure (32% female), 1235 (31%) had CS after acute myocardial infarction and 2688 (69%) had HF-CS. Median sequential organ failure assessment scores did not differ by sex. Women with HF-CS had shorter CICU lengths of stay (4.5 versus 5.4 days; P<0.0001) and shorter overall lengths of hospital stay (10.9 versus 12.8 days; P<0.0001) than men. Women with HF-CS were less likely to receive pulmonary artery catheters (50% versus 55%; P<0.01) and mechanical circulatory support (26% versus 34%; P<0.0001) compared with men. Women with HF-CS had higher in-hospital mortality than men, even after adjusting for age, illness severity, and comorbidities (34% versus 23%; odds ratio, 1.76 [95% CI, 1.42-2.17]). In contrast, there were no significant sex differences in utilization of advanced CICU monitoring and interventions, or mortality, among patients with CS after acute myocardial infarction. CONCLUSIONS: Women with HF-CS had lower use of pulmonary artery catheters and mechanical circulatory support, shorter CICU lengths of stay, and higher in-hospital mortality than men, even after accounting for age, illness severity, and comorbidities. These data highlight the need to identify underlying reasons driving the differences in treatment decisions, so outcomes gaps in HF-CS can be understood and eliminated.

Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal and synaptic regulation, and stress hormones. Multiomic factor and gene network analyses provided the underlying genomic structure. Single nucleus RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) signals in neuronal and non-neuronal cell types. Analyses of brain-blood intersections in >50,000 UK Biobank participants were conducted along with fine-mapping of the results of PTSD and MDD genome-wide association studies to distinguish risk from disease processes. Our data suggest shared and distinct molecular pathology in both disorders and propose potential therapeutic targets and biomarkers.

Emergency Department SpO2/FiO2 Ratios Correlate with Mechanical Ventilation and Intensive Care Unit Requirements in COVID-19 Patients.

Background: Patients with coronavirus 2019 (COVID-19) are at high risk for respiratory dysfunction. The pulse oximetry/fraction of inspired oxygen (SpO2/FiO2) ratio is a non-invasive assessment of respiratory dysfunction substituted for the PaO2:FiO2 ratio in Sequential Organ Failure Assessment scoring. We hypothesized that emergency department (ED) SpO2/FiO2 ratios correlate with requirement for mechanical ventilation in COVID-19 patients. Our objective was to identify COVID-19 patients at greatest risk of requiring mechanical ventilation, using SpO2/FiO2 ratios. Methods: We performed a retrospective review of patients admitted with COVID-19 at two hospitals. Highest and lowest SpO2/FiO2 ratios (percent saturation/fraction of inspired O2) were calculated on admission. We performed chi-square, univariate, and multiple regression analysis to evaluate the relationship of admission SpO2/FiO2 ratios with requirement for mechanical ventilation and intensive care unit (ICU) care. Results: A total of 539 patients (46% female; 84% White), with a mean age 67.6 ± 18.6 years, met inclusion criteria. Patients who required mechanical ventilation during their hospital stay were statistically younger in age (P = 0.001), had a higher body mass index (P < .001), and there was a higher percentage of patients who were obese (P = 0.03) and morbidly obese (P < .001). Shortness of breath, cough, and fever were the most common presenting symptoms with a median temperature of 99°F. Average white blood count was higher in patients who required ventilation (P = <0.001). A highest obtained ED SpO2/FiO2 ratio of ≤300 was associated with a requirement for mechanical ventilation. A lowest obtained ED SpO2/FiO2 ratio of ≤300 was associated with a requirement for intensive care unit care. There was no statistically significant correlation between ED SpO2/FiO2 ratios >300 and mechanical ventilation or intensive care unit (ICU) requirement. Conclusion: The ED SpO2/FiO2 ratios correlated with mechanical ventilation and ICU requirements during hospitalization for COVID-19. These results support ED SpO2/FiO2 as a possible triage tool and predictor of hospital resource requirements for patients admitted with COVID-19. Further investigation is warranted.

Validating the Supraorbital Notch-Nasion-Supraorbital Notch Angle as a Marker for Metopic Craniosynostosis Severity.

OBJECTIVE: Metopic craniosynostosis (MCS) can be difficult to differentiate from metopic ridge (MR) or normal frontal morphology. This study assess whether the supraorbital notch-nasion-supraorbital notch (SNS) angle can help identify MCS. METHODS: Records of 212 patients with preoperative three-dimensional computed tomography scans were examined. The SNS angles, surgeon craniofacial dysmorphology rankings, and CranioRate metopic severity scores (MSSs) were compared with the Spearman rank correlation coefficient. Receiver operating characteristic (ROC) curves with Youden J-statistic and cross-validation of regression models assessed the ability of these measures to predict surgery. RESULTS: A total of 212 patients were included, consisting of 78 MCS, 37 MR, and 97 controls. Both the mean SNS angle (MCS: 111.7 ± 10.7 degrees, MR: 126.0 ± 8.2 degrees, controls: 130.7 ± 8.8 degrees P < 0.001) and MSS (MCS: 5.9 ± 2.0, MR: 1.4 ± 1.9, controls: 0.2 ± 1.9, P < 0.001) were different among the cohorts. The mean SNS angle (111.5 ± 10.7 versus 129.1 ± 8.8, P < 0.001) was lower in those who had surgery and CranioRate score (5.9 ± 2.1 versus 0.8 ± 2.2, P < 0.001) was higher in those who underwent surgery. SNS angles were positively correlated with surgeon craniofacial dysmorphology rankings ( r = 0.41, P < 0.05) and CranioRate MSS ( r = 0.54, P < 0.05). The ROC curve requiring high sensitivity revealed an SNS angle of 124.8 degrees predicted surgery with a sensitivity of 88.7% and a specificity of 71.3%. A ROC curve using the CranioRate MCC values ≥3.19 predicted surgery with 88.7% sensitivity and 94.7% specificity. CONCLUSION: Orbital dysmorphology in patients with MCS is well captured by the supraorbital-nasion angle. Both the SNS angle and CranioRate MSS scores accurately predict surgical intervention.

Promises and Challenges of populational Proteomics in Health and Disease.

Advances in proteomic assay technologies have significantly increased coverage and throughput, enabling recent increases in the number of large-scale population-based proteomic studies of human plasma and serum. Improvements in multiplexed protein assays have facilitated the quantification of thousands of proteins over a large dynamic range, a key requirement for detecting the lowest-ranging, and potentially the most disease-relevant, blood-circulating proteins. In this perspective, we examine how populational proteomic datasets in conjunction with other concurrent omic measures can be leveraged to better understand the genomic and non-genomic correlates of the soluble proteome, constructing biomarker panels for disease prediction, among others. Mass spectrometry workflows are discussed as they are becoming increasingly competitive with affinity-based array platforms in terms of speed, cost, and proteome coverage due to advances in both instrumentation and workflows. Despite much success, there remain considerable challenges such as orthogonal validation and absolute quantification. We also highlight emergent challenges associated with study design, analytical considerations, and data integration as population-scale studies are run in batches and may involve longitudinal samples collated over many years. Lastly, we take a look at the future of what the nascent next-generation proteomic technologies might provide to the analysis of large sets of blood samples, as well as the difficulties in designing large-scale studies that will likely require participation from multiple and complex funding sources and where data sharing, study designs, and financing must be solved.