Hyperangulated versus Macintosh blades for intubation with videolaryngoscopy in ICU: the randomised multicentre INVIBLADE-ICU trial study protocol.

INTRODUCTION: Compared with the operating room, tracheal intubations in the intensive care unit (ICU) are associated with worsened glottic view, decreased first-time success rate and increase in the technical difficulty of intubation and incidence of complications. Videolaryngoscopes (VLs) have been proposed to improve airway management, and while recent studies have confirmed that VLs improve intubation conditions in this patient population, there remains a lack of clarity regarding the selection between a standard Macintosh blade or a hyperangulated one, to determine which yields the best outcomes. The purpose of this study was to compare successful intubation on the first attempt with the Macintosh VL versus the hyperangulated VL during tracheal intubation in ICU patients. We hypothesise that tracheal intubation using the hyperangulated VL will improve the frequency of successful intubation on the first attempt. METHODS AND ANALYSIS: The INtubation VIdeolaryngoscopy BLADE-ICU trial is a prospective, multicentre, open-label, interventional, randomised, controlled superiority study conducted in 29 ICUs in Spain. Patients will be randomly assigned in a 1:1 ratio to undergo intubation using a Macintosh VL (control group) or a hyperangulated VL (experimental group) for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcomes include the time to intubation, attempts for successful intubation, laryngoscopic vision assessed with the modified Cormack-Lehane scale, the need for adjuvant airway devices for intubation, difficulty assessed by the anaesthesiologist and complications during tracheal intubation. Enrolment began on 1 May 2024 and is expected to be completed in 2025. ETHICS AND DISSEMINATION: The study protocol was approved on 29 February 2024, by the Ethics Committee of Galicia (CEImG, code No. 2024-031).The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT06322719.

Applying Watson's Theory of Transpersonal Caring to Situate Caregiver Accounts of End-of-Life Experiences Within a Caregiving Context.

End-of life-experiences, including profoundly meaningful dreams, visions, and sensations, may be experienced by caregivers at the time of a patient's death, yet few caregivers feel comfortable discussing these experiences with colleagues or other members of the care unit. This article presents findings from a descriptive qualitative study of end-of-life experiences reported by caregivers and frames these experiences within Watson's Theory of Transpersonal Caring, which is a holistic approach to health care that emphasizes the transpersonal caring relationship. Watson's Theory is particularly useful for framing end-of-life experiences in a caregiving context as it avoids debates about the nature of these experiences and emphasizes their therapeutic value in human caring. This article also argues that it is time for open discussions about end-of-life experiences reported by caregivers and what they might teach us about death and dying.

Efficacy of laser hair removal in hidradenitis suppurativa: A systematic review and meta-analysis.

OBJECTIVES: Hidradenitis suppurativa (HS) is a chronic inflammatory condition characterized by painful nodules, draining tunnels, and fibrotic scarring in intertriginous, hair-bearing areas. The pathogenesis involves follicular occlusion and subsequent rupture, leading to uncontrolled inflammation. Treatment options for HS are limited and lack universal effectiveness. Laser hair removal (LHR) has been explored as a potential treatment; however, the efficacy and appropriate laser modalities remain unclear. This systematic review examined the efficacy and adverse effects of LHR in HS. METHODS: A comprehensive literature search was conducted from inception to September 2023 in Ovid MEDLINE, Ovid Embase, and The Cochrane Library (Wiley) with predefined inclusion and exclusion criteria, and a meta-analysis was conducted. RESULTS: Ten studies were selected (n = 227 total patients) and included six randomized controlled trials, two nonrandomized experimental studies, and two case series. Various laser modalities, including long-pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) (n = 115), intense pulsed light (n = 18), Alexandrite (n = 54), intralesional 1064 nm diode (n = 20), and combined fractional CO2 and long-pulsed Nd:YAG laser (n = 20), consistently demonstrated significant improvement in HS disease severity, irrespective of the disease scoring method used. Minimal adverse effects (primarily mild pain and erythema) were reported. A meta-analysis of three studies utilizing long-pulsed Nd:YAG laser demonstrated a standardized mean difference in disease severity of -1.68 (95% confidence interval: -2.99; -0.37), favoring treatment with LHR for HS. CONCLUSIONS: Hair follicles are key in HS pathogenesis and all included studies showed a significant improvement in HS disease severity after LHR regardless of the laser device used, likely related to hair follicle unit destruction. HS is a complex and heterogenous condition, and multiple disease scoring methods complicate outcome comparisons across studies. However, LHR, utilizing various techniques, is an effective treatment option for HS with minimal adverse effects.

Feasibility of an Exoskeleton Armrest to Improve Ergonomics during Endoscopic Sinus and Skull Base Surgery.

OBJECTIVE: The main objective of this study was to develop and evaluate the feasibility and effectiveness of a novel exoskeleton system designed to provide ergonomic assistance to surgeons while preserving or improving the quality of endoscopic sinus and skull base surgical procedures. METHODS: To evaluate the functionality and ergonomic characteristics of the device, five experiments were conducted in different and increasingly realistic scenarios: silicone model of the nasal cavity, freshly frozen cadavers and finally in a real surgery. Each volunteer's task was recorded and timed. The National Aeronautics and Space Administration Task Load Index (NASA-TLX) rating scale was used to estimate the surgeons' workload while performing the tasks. RESULTS: Twenty-five volunteers took part in the experiments. Volunteers perceived more comfort and less fatigue and pain when using the armrest than when not using the device (3.3, SD 1.75 vs. 5.9 SD 1.49; p = 0.02). Participants found the device intuitive, comfortable, and improving accuracy and stability with endoscope use. CONCLUSION: A new system that provides ergonomic assistance to surgeons was tested in simulation surgery with acceptable usability. Initial results in terms of pain and fatigue reduction and efficiency were excellent, justifying further research into this technology. LEVEL OF EVIDENCE: NA Laryngoscope, 134:79-86, 2024.

Perioperative Management of Pediatric Patients with Moyamoya Arteriopathy.

Pediatric patients with moyamoya arteriopathy are at high risk for developing new onset transient or permanent neurologic deficits secondary to cerebral hypoperfusion, particularly in the perioperative period. It is therefore essential to carefully manage these patients in a multidisciplinary, coordinated effort to reduce the risk of new permanent neurologic deficits. However, little has been published on perioperative management of pediatric patients with moyamoya, particularly in the early postoperative period during intensive care unit admission. Our pediatric neurocritical care team sought to create a multidisciplinary periprocedural evidence- and consensus-based care pathway for high-risk pediatric patients with moyamoya arteriopathy undergoing anesthesia for any reason to decrease the incidence of periprocedural stroke or transient ischemic attack (TIA). We reviewed the literature to identify risk factors associated with perioperative stroke or TIA among patients with moyamoya and to gather data supporting specific perioperative management strategies. A multidisciplinary team from pediatric anesthesia, neurocritical care, nursing, child life, neurosurgery, interventional neuroradiology, neurology, and hematology created a care pathway for children with moyamoya undergoing anesthesia, classifying them as either high or standard risk, and applying an individualized perioperative management plan to high-risk patients. The incidence of neurologic sequelae before and after pathway implementation will be compared in future studies.

Ambulatory palliative care among patients with hidradenitis suppurativa: A qualitative study.

Background: Patients with hidradenitis suppurativa (HS) experience high physical and emotional symptom burden and may benefit from palliative care interventions, though no studies have explored the unmet palliative care needs in this population. Objective: This case series aimed to qualitatively evaluate unmet needs and palliative care interventions among patients with HS who were referred to palliative care. Methods: We reviewed medical records of patients with HS who were referred from an HS specialty clinic and seen in an interprofessional palliative care ambulatory clinic. Palliative care notes were qualitatively analyzed inductively and deductively to identify themes characterizing unmet needs and palliative care interventions. Results: Thirteen patients with HS (median [IQR] age, 38 [31-45] years; 11 [85%] women; 11 [85%] Black) were referred and seen in a palliative care specialty clinic. Topics discussed included uncontrolled HS pain, housing insecurity, and emotional distress. Palliative care interventions included a thorough assessment of pain, multimodal pain management approaches, social worker weekly check-ins, and management of psychotropic medications. Limitations: Small study at a single tertiary center. Conclusions: Care models integrating palliative care approaches with multidisciplinary support services may reduce disease burden in a subset of patients with HS.

The case for transitional services and programs for older adults reentering society: a narrative review of US departments of correction and recommendations.

PURPOSE: Older adults who are or have been incarcerated constitute a growing population in the USA. The complex health needs of this group are often inadequately addressed during incarceration and equally so when transitioning back to the community. The purpose of this paper is to discuss the literature on challenges older adults (age 50 and over) face in maintaining health and accessing social services to support health after an incarceration and to outline recommendations to address the most urgent of these needs. DESIGN/METHODOLOGY/APPROACH: This study conducted a narrative literature review to identify the complex health conditions and health services needs of incarcerated older adults in the USA and outline three primary barriers they face in accessing health care and social services during reentry. FINDINGS: Challenges to healthy reentry of older adults include continuity of health care; housing availability; and access to health insurance, disability and other support. The authors recommend policy changes to improve uniformity of care, development of support networks and increased funding to ensure that older adults reentering communities have access to resources necessary to safeguard their health and safety. ORIGINALITY/VALUE: This review presents a broad perspective of the current literature on barriers to healthy reentry for older adults in the USA and offers valuable system, program and policy recommendations to address those barriers.

Angiostatic Peptide, Endostatin, Predicts Severity in Pediatric Congenital Heart Disease-Associated Pulmonary Hypertension.

Background Endostatin, an angiogenic inhibitor, is associated with worse pulmonary arterial hypertension (PAH) outcomes in adults and poor lung growth in children. This study sought to assess whether endostatin is associated with disease severity and outcomes in pediatric PAH. Methods and Results Serum endostatin was measured in cross-sectional (N=160) and longitudinal cohorts (N=64) of pediatric subjects with PAH, healthy pediatric controls and pediatric controls with congenital heart disease (CHD) (N=54, N=15), and adults with CHD associated PAH (APAH-CHD, N=185). Outcomes, assessed by regression and Kaplan-Meier analysis, included hemodynamics, change in endostatin over time, and transplant-free survival. Endostatin secretion was evaluated in pulmonary artery endothelial and smooth muscle cells. Endostatin was higher in those with PAH compared with healthy controls and controls with CHD and was highest in those with APAH-CHD. In APAH-CHD, endostatin was associated with a shorter 6-minute walk distance and increased mean right atrial pressure. Over time, endostatin was associated with higher pulmonary artery pressure and pulmonary vascular resistance index, right ventricular dilation, and dysfunction. Endostatin decreased with improved hemodynamics over time. Endostatin was associated with worse transplant-free survival. Addition of endostatin to an NT-proBNP (N-terminal pro-B-type natriuretic peptide) based survival analysis improved risk stratification, reclassifying subjects with adverse outcomes. Endostatin was secreted primarily by pulmonary artery endothelial cells. Conclusions Endostatin is associated with disease severity, disease improvement, and worse survival in APAH-CHD. Endostatin with NT-proBNP improves risk stratification, better predicting adverse outcomes. The association of elevated endostatin with shunt lesions suggests that endostatin could be driven by both pulmonary artery flow and pressure. Endostatin could be studied as a noninvasive prognostic marker, particularly in APAH-CHD.

Pediatric pulmonary hypertension: insulin-like growth factor-binding protein 2 is a novel marker associated with disease severity and survival.

BACKGROUND: Insulin-like growth factors (IGFs), and their binding proteins (IGFBPs), play a significant role in cardiovascular function and may influence the pathobiology of PAH. We determined the diagnostic and prognostic value of IGF1 and IGFBP2 in pediatric PAH. METHODS: Serum was analyzed by ELISA for IGF1 and IGFBP2 in pediatric PAH subjects from the NHLBI PAH Biobank (PAHB, n = 175) and a cohort of asthmatic subjects (n = 46, age 0-21 years) as a chronic pediatric pulmonary disease control. Biomarkers were analyzed with demographic and clinical variables for PAH severity. RESULTS: Serum IGF1 was significantly lower in PAH compared to controls, while IGFBP2 was elevated in PAH subjects compared to controls. In the PAHB, IGF1 was negatively associated with mPAP and PVR, while IGFBP2 was positively associated with PVR and negatively associated with cardiac output and 6-min walk distance. Higher IGFBP2 levels were associated with use of prostacyclin therapy. IGFBP2 was associated with death, transplant, or palliative shunt with a Cox proportional hazard ratio of 8.8 (p < 0.001) but not IGF1 (p = 0.13). CONCLUSIONS: Circulating IGFBP2 is a novel marker for pediatric PAH, which is associated with worse functional status, and survival. IGF axis dysregulation may be an important mechanistic target in pediatric pulmonary arterial hypertension. IMPACT: Pediatric pulmonary hypertension is a severe disease, with poorly understood pathobiology. There are few studies looking at the pathobiology of pulmonary hypertension only in children. The IGF axis is dysregulated in pediatric pulmonary arterial hypertension. IGF axis dysregulation, with increased IGFBP2, is associated with worse clinical outcomes in pediatric pulmonary artery hypertension. IGF axis dysregulation gives new insight into the disease process and may be a mechanistic or therapeutic target.

Correction: Endostatin and ST2 are predictors of pulmonary hypertension disease course in infants.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Endostatin and ST2 are predictors of pulmonary hypertension disease course in infants.

INTRODUCTION: Pulmonary hypertension (PH) is a common comorbidity of cardiopulmonary disease. Endostatin, an inhibitor of angiogenesis, is elevated in neonates with lung disease. ST2 is a heart failure biomarker correlated with PH in adults. We hypothesized that these biomarkers may be useful in diagnosing PH and categorizing its severity in infants. METHODS: Endostatin, ST2, and NT-proBNP plasma concentrations from 26 infants with PH and 21 control infants without PH were correlated with echocardiographic and clinical features using regression models over time. RESULTS: Endostatin, ST2, and NT-proBNP concentrations were elevated in PH participants versus controls (p < 0.0001). Endostatin was associated with right ventricular dysfunction (p = 0.014), septal flattening (p = 0.047), and pericardial effusion (p < 0.0001). ST2 concentrations predicted right to left patent ductus arteriosus flow (p = 0.009). NT-proBNP was not associated with PH features. CONCLUSIONS: Endostatin and ST2 concentrations were associated with echocardiographic markers of worse PH in infants and may be better predictors than existing clinical standards.

Physician Assistant Students' Knowledge of Zika Virus: A Pilot Study.

OBJECTIVE: The aim of this study was to assess physician assistant students' knowledge about the screening, transmission, management, and prevention of Zika virus infection. BACKGROUND: It is important for health care providers in the United States to recognize the symptoms of Zika so that they can screen, diagnose, and or treat persons exposed to or infected by the virus. Physician assistant students, on completion of their educational program and passing their board examinations, provide care for patients in primary care or specialty settings where they may treat patients who either have the virus or post-virus exposure. METHODS: A convenience sample of 37 students enrolled in a physician assistant studies program in the Midwestern United States completed an in-person self-administered paper-and-pencil questionnaire that tested their knowledge about Zika virus infection. RESULTS: All the respondents knew that the disease is of viral origin; however, only 89% knew that mosquitoes were the natural host. Primary modes of transmission were identified as sexual contact and blood transfusion (47% and 44% of respondents respectively); 47% incorrectly identified amniotic fluid as a transmission mode. More than half (61%) knew that health care providers should ask pregnant women about any possible virus exposure before and during pregnancy at each prenatal visit. Most respondents knew that muscle/joint pain (67%) was one of the symptoms of Zika infection, but only 39%, 25%, and 19% also identified low-grade fever, maculopapular rash, and conjunctivitis respectively as other symptoms. Some participants incorrectly identified antivirals (44%) and nonsteroidal anti-inflammatory medications (36%) rather than the recommended treatments of pain relief (30%) and fever relief (42%) medications for clinical management of the disease.

Tau Is Elevated in Pediatric Patients on Extracorporeal Membrane Oxygenation.

Neurologic injury is a known and feared complication of extracorporeal membrane oxygenation (ECMO). Neurologic biomarkers may have a role in assisting in early identification of such. Axonal biomarker tau has not been investigated in the pediatric ECMO population. The objective of this study is to evaluate plasma levels of tau in pediatric patients supported with ECMO. Eighteen patients requiring ECMO support in a quaternary pediatric intensive care unit at a university-affiliated children's hospital from October 2015 to February 2017 were enrolled. Patients undergoing extracorporeal cardiopulmonary resuscitation or recent history of bypass were excluded. Plasma tau was measured using enzyme-linked immunosorbent assay. Neuroimaging was reviewed for acute neurologic injury, and tau levels were analyzed to assess for correlation. Tau was significantly higher in ECMO patients than in control subjects. Sixty-one percent of subjects had evidence of acute brain injury on neuroimaging, but tau level did not correlate with injury. Subjects with multifocal injury all experienced infarction and had significantly higher tau levels on ECMO day 3 than patients with isolated injury. In addition, peak tau levels of neuro-injured subjects were compared with controls and noninjured ECMO subjects using receiver operating curve analysis. This study demonstrates preliminary evidence of axonal injury in pediatric ECMO patients.

Avoiding the Major Causes of Death: Does Childhood Misfortune Reduce the Likelihood of Being Disease Free in Later Life?

Objectives: Although previous research reveals the detrimental effects of early misfortune on the development of chronic diseases in later life, few studies have investigated its effects on remaining disease free. This study draws on cumulative inequality theory to investigate whether experiencing childhood misfortune reduces the likelihood of remaining disease free over time. Method: This study utilizes five waves of data from the Health and Retirement Study to test whether five domains of childhood misfortune predict being disease free at baseline (2004) and developing disease over time (2004-2012). Results: Respondents reporting risky parental behaviors during childhood were less likely to be disease free at baseline and had an increased risk of disease onset over time, the latter driven by having a guardian who smoked in combination with more pack-years smoked in adulthood. Furthermore, we find that adult resources, that is wealth, help to mitigate the noxious effects of other misfortunes, notably poor socioeconomic conditions. Discussion: Consistent with cumulative inequality theory, these findings reveal that experiencing multiple types of misfortune during childhood decreases the likelihood of remaining disease free in later life, but engaging in health behaviors, such as physical activity, can help to ameliorate some of the noxious effects of early misfortune.

Human AML activates the aryl hydrocarbon receptor pathway to impair NK cell development and function.

Acute myeloid leukemia (AML) can evade the mouse and human innate immune system by suppressing natural killer (NK) cell development and NK cell function. This is driven in part by the overexpression of microRNA (miR)-29b in the NK cells of AML patients, but how this occurs is unknown. In the current study, we demonstrate that the transcription factor aryl hydrocarbon receptor (AHR) directly regulates miR-29b expression. We show that human AML blasts activate the AHR pathway and induce miR-29b expression in NK cells, thereby impairing NK cell maturation and NK cell function, which can be reversed by treating NK cells with an AHR antagonist. Finally, we show that inhibition of constitutive AHR activation in AML blasts lowers their threshold for apoptosis and decreases their resistance to NK cell cytotoxicity. Together, these results identify the AHR pathway as a molecular mechanism by which AML impairs NK cell development and function. The results lay the groundwork in establishing AHR antagonists as potential therapeutic agents for clinical development in the treatment of AML.

Trajectory of inflammatory and microglial activation markers in the postnatal rabbit brain following intrauterine endotoxin exposure.

BACKGROUND: Maternal infection is a risk factor for periventricular leukomalacia and cerebral palsy (CP) in neonates. We have previously demonstrated hypomyelination and motor deficits in newborn rabbits, as seen in patients with cerebral palsy, following maternal intrauterine endotoxin administration. This was associated with increased microglial activation, primarily involving the periventricular region (PVR). In this study we hypothesized that maternal intrauterine inflammation leads to a pro-inflammatory environment in the PVR that is associated with microglial activation in the first 2 postnatal weeks. METHODS: Timed pregnant New Zealand white rabbits underwent laparotomy on gestational day 28 (G28). They were randomly divided to receive lipopolysaccharide (LPS; 20µg/kg in 1mL saline) (Endotoxin group) or saline (1mL) (control saline, CS group), administrated along the wall of the uterus. The PVR from the CS and Endotoxin kits were harvested at G29 (1day post-injury), postnatal day1 (PND1, 3day post-injury) and PND5 (7days post-injury) for real-time PCR, ELISA and immunohistochemistry. Kits from CS and Endotoxin groups underwent longitudinal MicroPET imaging, with [11C]PK11195, a tracer for microglial activation. RESULTS: We found that intrauterine endotoxin exposure resulted in pro-inflammatory microglial activation in the PVR of rabbits in the first postnatal week. This was evidenced by increased TSPO (translocator protein) expression co-localized with microglia/macrophages in the PVR, and changes in the microglial morphology (ameboid soma and retracted processes). In addition, CD11b level significantly increased with a concomitant decline in the CD45 level in the PVR at G29 and PND1. There was a significant elevation of pro-inflammatory cytokines and iNOS, and decreased anti-inflammatory markers in the Endotoxin kits at G29, PND1 and PND5. Increased [11C]PK11195 binding to the TSPO measured in vivo by PET imaging in the brain of Endotoxin kits was present up to PND14-17. CONCLUSIONS: Our results indicate that a robust pro-inflammatory microglial phenotype/brain milieu commenced within 24h after LPS exposure and persisted through PND5 and in vivo TSPO binding was found at PND14-17. This suggests that there may be a window of opportunity to treat after birth. Therapies aimed at inducing an anti-inflammatory phenotype in microglia might promote recovery in maternal inflammation induced neonatal brain injury.

Cerebrovascular blood pressure autoregulation monitoring and postoperative transient ischemic attack in pediatric moyamoya vasculopathy.

BACKGROUND: Children with moyamoya vasculopathy are at high risk of perioperative cerebral ischemia or hyperperfusion. Maintaining blood pressure within the range of functional cerebrovascular blood pressure autoregulation might reduce the risk of perioperative neurologic injury. AIMS: We tested whether blood pressure autoregulation is associated with postoperative transient ischemic attack in a study of patients with pediatric moyamoya vasculopathy. METHODS: We conducted an observational study of 15 pediatric patients undergoing surgical revascularization with pial synangiosis. Nine patients had bilateral moyamoya and 6 had unilateral moyamoya. We measured autoregulatory vasoreactivity intraoperatively and during the first postoperative night with the hemoglobin volume index, a value derived from near-infrared spectroscopy. We also identified the optimal mean arterial blood pressure at which autoregulation was most robust in each patient. RESULTS: Of the 15 children monitored, 3 with bilateral moyamoya and one with unilateral moyamoya experienced a transient ischemic attack. Poorer autoregulation during surgery was associated with postoperative transient ischemic attack among those with bilateral vasculopathy (P = .048, difference in hemoglobin volume index medians: 0.023, 95% confidence interval: 0.003-0.071). This relationship was not observed with postoperative autoregulation. The optimal mean arterial blood pressure was identifiable during surgery in all monitored patients, varied among patients, and often differed between the intraoperative and postoperative periods. CONCLUSION: Dysfunctional intraoperative autoregulation may increase the risk of TIA in patients with pediatric moyamoya vasculopathy. The blood pressure range that supports autoregulation appears to vary among patients. Using autoregulation monitoring to guide individualized blood pressure goals should be studied as a potential method to reduce perioperative neurologic morbidity in pediatric patients with moyamoya.