Airway management of a patient with linear immunoglobulin A bullous dermatosis: A case report.

BACKGROUND: There is limited literature on managing the airway of patients with linear immunoglobulin A (IgA) bullous dermatosis, a rare mucocutaneous disorder that leads to the development of friable bullae. Careful clinical decision making is necessary when there is a risk of bleeding into the airway, and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios, especially when confronted with an unusual cause for bleeding. CASE SUMMARY: A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous dermatosis. The diagnosis of IgA dermatosis was recent, and the patient had been lost to follow-up. The severity of the disease and extent of airway involvement was unknown at the time of the surgery. Significant airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating room. The patient required transfer to the intensive care unit where a multidisciplinary team was involved in her case. The patient was extubated on postoperative day 4. CONCLUSION: A multidisciplinary approach to treating this disease is the best course of action before a surgical procedure. In our case, key communication between the surgery, anesthesia, and dermatology teams led to the quick and safe treatment of our patient's disease. Ambulatory surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.

Neuronal intranuclear inclusion disease in New Zealand: A novel discovery.

Neuronal intranuclear inclusion disease, caused by a GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC, is a rare neurodegenerative condition with highly variable clinical manifestations. In recent years, the number of reported cases have increased dramatically in East Asia. We report the first four genetically confirmed cases of neuronal intranuclear inclusion disease in New Zealand, all having Polynesian ancestry (three New Zealand Maori and one Cook Island Maori). Phenotypically, they resemble cases reported from recent large East Asian cohorts.

Effect of Dexmedetomidine on Incidence of Hypertension Following Repair of Coarctation of the Aorta.

OBJECTIVE: Recent literature suggests a potential role for dexmedetomidine in reducing the incidence and severity of hypertension following repair of coarctation of the aorta (CoA). The primary aim of this study was to assess the association between dexmedetomidine use and the incidence of hypertension following repair of CoA in pediatric patients. METHODS: This was a single-center, retrospective cohort study in patients younger than 19 years who underwent surgical repair of CoA between January 1, 2016, and September 30, 2021. Patients were divided into 2 groups: dexmedetomidine initiation within the first 3 hours after surgery or no dexmedetomidine. The primary outcome was incidence of hypertension within the first 4 to 24 hours after repair. Secondary outcomes included the incidence of hypotension and bradycardia. RESULTS: A total of 80 patients were included, 25 (31.25%) received dexmedetomidine. Median age at the time of procedure was 26 days (IQR, 13-241) in the dexmedetomidine group and 14 days (IQR, 8-53) in the no dexmedetomidine group (p = 0.014). The primary outcome of hypertension was met in 7 patients (28%) in the dexmedetomidine group and 12 patients (21.8%) in the no dexmedetomidine group, p = 0.547. The only variable found to be associated with the incidence of hypertension was age greater than 30 days at the time of procedure. More patients who received dexmedetomidine experienced bradycardia. There was no difference in the incidence of hypotension. CONCLUSIONS: There was no association between the use of dexmedetomidine and the incidence of -hypertension following repair of CoA in pediatric patients.

Current Practices and Safety of Medication Use During Pediatric Rapid Sequence Intubation.

OBJECTIVES: This study aimed to characterize medication-related practices during and immediately -following rapid sequence intubation (RSI) in pediatric care units across the United States and to evaluate adverse drug events. METHODS: This was a multicenter, observational study of medication practices surrounding intubation in pediatric and neonatal intensive care unit (NICU) and emergency department patients across the United States. RESULTS: A total of 172 patients from 13 geographically diverse institutions were included. Overall, 24%, 69%, and 50% received preinduction, induction, and neuromuscular blockade, respectively. Induction and neuromuscular blocking agent (NMBA) use was low in NICU patients (52% and 23%, respectively), whereas nearly all patients intubated outside of the NICU received both (98% and 95%, respectively). NICU patients who received RSI medications were older and weighed more. Despite infrequent use of atropine (21%), only 3 patients developed bradycardia after RSI. Of the 119 patients who received an induction agent, fentanyl (67%) and midazolam (34%) were administered most frequently. Hypotension and hypertension occurred in 23% and 24% of patients, respectively, but were not associated with a single induction agent. Etomidate use was low and not associated with development of adrenal insufficiency. Rocuronium was the most used NMBA (78%). Succinylcholine use was low (11%) and administered despite hyperkalemia in 2 patients. Postintubation sedation and analgesia were not used or inadequate based on timing of initiation in many patients who received a non-depolarizing NMBA. CONCLUSIONS: Medication practices surrounding pediatric RSI vary across the United States and may be influenced by patient location, age, and weight.

East Antarctic warming forced by ice loss during the Last Interglacial.

During the Last Interglacial (LIG; 129-116 thousand years before present), the Antarctic ice sheet (AIS) was 1 to 7 m sea level equivalent smaller than at pre-industrial. Here, we assess the climatic impact of partial AIS melting at the LIG by forcing a coupled climate model with a smaller AIS and the equivalent meltwater input around the Antarctic coast. We find that changes in surface elevation induce surface warming over East Antarctica of 2 to 4 °C, and sea surface temperature (SST) increases in the Weddell and Ross Seas by up to 2 °C. Meltwater forcing causes a high latitude SST decrease and a subsurface (100-500 m) ocean temperature increase by up to 2 °C in the Ross Sea. Our results suggest that the combination of a smaller AIS and enhanced meltwater input leads to a larger sub-surface warming than meltwater alone and induces further Antarctic warming than each perturbation separately.

Role of Preoperative Nerve Conduction Studies for Penetrating Hand Injuries Involving the Median Palmar Cutaneous Nerve.

Penetrating lacerations to the hand are a common cause of nerve injury and can lead to debilitating pain and numbness in the distribution of the nerve affected. Owing to an overlap in the cutaneous innervation from different sensory nerves, clinically identifying the injured nerve can be difficult. We present a novel case of isolated injury to the palmar cutaneous nerve from a penetrating knife injury which was detected using 'comparison waveform' nerve conduction studies. Using this technique, we can isolate injuries to the palmar cutaneous branch of the median nerve (PCBmdn) from the median nerve, dorsal radial sensory nerve, and lateral antebrachial cutaneous nerve. In addition, sensory nerve testing identified conduction block as the mechanism of injury, which resolved after surgery at 8 weeks postoperatively. Preoperative nerve conduction study can discern the level of nerve injury to PCBmdn only, thus eliminating the need for median and radial nerve exploration at the forearm, unnecessary incisions, pain, and scarring. The objective of this case report is to illustrate the value of preoperative comparison waveform nerve conduction study, particularly the PCBmdn, in patients presenting with neurologic deficits who have sustained penetrating lacerations to the hand.

Signatures of Superradiance as a Witness to Multipartite Entanglement.

Generation and detection of entanglement is at the forefront of most quantum information technologies. There is a plethora of techniques that reveal entanglement on the basis of only partial information about the underlying quantum state, including entanglement witnesses. Superradiance refers to the phenomenon of highly synchronized photon emission from an ensemble of quantum emitters that is caused by correlations among the individual particles and has been connected by Dicke himself to the presence of multipartite entangled states. We investigate this connection in a quantitative way and discuss whether or not signatures of superradiance from semiconductor nanolasers, manifesting themselves as a modification of the spontaneous-emission time, can be interpreted as a witness to detect entanglement in the underlying state of the emitters.

Immune responses to citrullinated and homocitrullinated peptides in healthy donors are not restricted to the HLA SE shared allele and can be selected into the memory pool.

Citrullination and homocitrullination are stress induced post-translational modifications (siPTMs) which can be recognized by T cells. Peripheral blood mononuclear cells isolated from healthy donors and rheumatoid arthritis (RA) patients were stimulated with nine siPTM-peptides. CD45RA/CD45RO depletion was employed to determine if peptide-specific responses are naïve or memory. Human leucocyte antigen (HLA)-DP4 and HLA-DR4 transgenic mice were immunized with siPTM-peptides and immune responses were determined with ex vivo ELISpot assays. The majority (24 out of 25) of healthy donors showed CD4 T cell-specific proliferation to at least 1 siPTM-peptide, 19 to 2 siPTM-peptides, 14 to 3 siPTM-peptides, 9 to 4 siPTM-peptides, 6 to 5 siPTM-peptides and 4 to 6 siPTM-peptides. More donors responded to Vim28-49cit (68%) and Bip189-208cit (75%) compared with Vim415-433cit (33%). In RA patients, the presentation of citrullinated epitopes is associated with HLA-SE alleles; however, we witnessed responses in healthy donors who did not express the SE allele. The majority of responding T cells were effector memory cells with a Th1/cytotoxic phenotype. Responses to Vim28-49cit and Eno241-260cit originated in the memory pool, while the response to Vim415-433cit was naïve. In the HLA-DP4 and HLA-DR4 transgenic models, Vim28cit generated a memory response. Peptide-specific T cells were capable of Epstein-Barr virus transformed lymphoblastoid cell line recognition suggesting a link with stress due to infection. These results suggest siPTM-peptides are presented under conditions of cellular stress and inflammation and drive cytotoxic CD4 T cell responses that aid in the removal of stressed cells. The presentation of such siPTM-peptides is not restricted to HLA-SE in both humans and animal models.

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated.

BACKGROUND & AIMS: The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers. METHOD: Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements. RESULTS: A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9 kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9 kPa (adjusted odds ratio = 3.19; 95% CI 1.95-5.20; p <0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio = 1.76; 95% CI 1.20-2.56; p = 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis. CONCLUSION: The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX. IMPACT AND IMPLICATIONS: Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients' metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate.

African Hydroclimate During the Early Eocene From the DeepMIP Simulations.

The early Eocene (∼56-48 Myr ago) is characterized by high CO2 estimates (1,200-2,500 ppmv) and elevated global temperatures (∼10°C-16°C higher than modern). However, the response of the hydrological cycle during the early Eocene is poorly constrained, especially in regions with sparse data coverage (e.g., Africa). Here, we present a study of African hydroclimate during the early Eocene, as simulated by an ensemble of state-of-the-art climate models in the Deep-time Model Intercomparison Project (DeepMIP). A comparison between the DeepMIP pre-industrial simulations and modern observations suggests that model biases are model- and geographically dependent, however, these biases are reduced in the model ensemble mean. A comparison between the Eocene simulations and the pre-industrial suggests that there is no obvious wetting or drying trend as the CO2 increases. The results suggest that changes to the land sea mask (relative to modern) in the models may be responsible for the simulated increases in precipitation to the north of Eocene Africa. There is an increase in precipitation over equatorial and West Africa and associated drying over northern Africa as CO2 rises. There are also important dynamical changes, with evidence that anticyclonic low-level circulation is replaced by increased south-westerly flow at high CO2 levels. Lastly, a model-data comparison using newly compiled quantitative climate estimates from paleobotanical proxy data suggests a marginally better fit with the reconstructions at lower levels of CO2.

Enoxaparin Reduces Catheter-associated Venous Thrombosis After Infant Cardiac Surgery.

BACKGROUND: Central venous catheter (CVC) related venous thrombosis (VT) after pediatric cardiac surgery increases morbidity and mortality. Although VT prevention using low-dose anticoagulation therapy has proven ineffective, anticoagulation therapy using high-dose enoxaparin to achieve a therapeutic anti-Xa level has not been studied. We hypothesized that high-dose enoxaparin would reduce VT after pediatric cardiac surgery. METHODS: Enoxaparin was administered to infants aged less than 150 days when postoperative CVC duration was anticipated to extend beyond 5 days. The primary outcome was the rate of VT, reexploration for bleeding, and postoperative red blood cell transfusions per 1000 CVC days. RESULTS: From 2012 to 2019, 157 infants were treated with enoxaparin. Infants were divided into two groups: (1) subtherapeutic (n = 51), in which therapeutic anti-Xa level (0.5 to 1.0 IU/mL) was not achieved; and (2) therapeutic (n = 106), in which therapeutic anti-Xa level was achieved. Baseline demographics demonstrated a lower age at operation in the therapeutic group. The subtherapeutic group had a higher VT rate per 1000 CVC days (8.2) compared with the therapeutic group (2.6; P = .005). Reexploration for bleeding was similar between groups. The number of postoperative red blood cell transfusions per 1000 CVC days was significantly greater in the subtherapeutic group (109.4 vs 81.6; P = .008). Multivariate analysis demonstrated that higher median anti-Xa levels reduced the risk of VT (odds ratio 0.02; 95% confidence interval, 0.001 to 0.63; P = .02). CONCLUSIONS: These data suggest that enoxaparin treatment resulting in a therapeutic anti-Xa level reduces postoperative CVC-associated VT without increasing bleeding complications.

The Rochester Relapse Risk Scale: Developing a Standardized Approach to Predicting Substance Relapse in Liver Transplant Candidates.

OBJECTIVES: Substance abuse is a risk factor for nonadherence and graft failure after orthotopic liver transplant. This study aimed to evaluate the ability of an internally developed tool, the Rochester Relapse Risk Scale, to predict substance relapse in liver transplant candidates. MATERIALS AND METHODS: This single-center, retrospective, observational study included adult patients evaluated for orthotopic liver transplant using the Rochester Relapse Risk Scale. Primary outcome was rate of substance relapse, as measured by the risk scale, which stratified patients into relapse risk levels based on the number of factors present. RESULTS: In total, 303 patients (71.6% men, 90.4% White, median age of 55 years [interquartile range, 49-60 y]) were included. Median follow-up time was 212 days (interquartile range, 73-661 d). Seventy-four patients (24.4%) relapsed at 127 days (interquartile range, 55-461 d) after evaluation, with 60.8% who relapsed within 6 months. Relapse rates correlated with assigned risk level, with 8.3% relapsing at low, 19.0% at low-moderate, 25.3% at moderate, 33.8% at moderate-high, and 40.0% at high risk. High-risk cohorts had significantly shorter median time to relapse versus low-risk cohorts (104 vs 154 days; P = .001). CONCLUSIONS: Assignment of relapse risk level according to the Rochester Relapse Risk Scale aligned with rates of relapse. Additional studies are needed to refine the tool, assess inter-rater reliability, and confirm findings in prospective, multicenter studies.

Observation of two-dimensional Anderson localisation of ultracold atoms.

Anderson localisation -the inhibition of wave propagation in disordered media- is a surprising interference phenomenon which is particularly intriguing in two-dimensional (2D) systems. While an ideal, non-interacting 2D system of infinite size is always localised, the localisation length-scale may be too large to be unambiguously observed in an experiment. In this sense, 2D is a marginal dimension between one-dimension, where all states are strongly localised, and three-dimensions, where a well-defined phase transition between localisation and delocalisation exists as the energy is increased. Here, we report the results of an experiment measuring the 2D transport of ultracold atoms between two reservoirs, which are connected by a channel containing pointlike disorder. The design overcomes many of the technical challenges that have hampered observation of localisation in previous works. We experimentally observe exponential localisation in a 2D ultracold atom system.

Escalation in Therapy Based on Intravenous Magnesium Sulfate Dosing in Pediatric Patients With Asthma Exacerbations.

OBJECTIVE: Our objective was to compare doses of intravenous magnesium sulfate and their association with escalations in therapy in children and adolescents presenting to the emergency department with an asthma exacerbation. METHODS: This was a retrospective cohort study among children who received both magnesium sulfate and standard of care therapy for asthma exacerbations. A classification and regression tree (CART) analysis was performed to identify a breakpoint in dose in which a difference in the primary outcome was present. The primary endpoint was need for escalation in therapy within 24 hours of initial magnesium sulfate dose, defined as need for invasive or non-invasive mechanical ventilation or need for adjunctive therapy, that is, epinephrine, terbutaline, aminophylline, theophylline, ketamine, heliox, or additional doses of magnesium sulfate. RESULTS: A total of 210 patients were included in the study. A CART analysis identified that a breakpoint of 27 mg/kg of magnesium was associated with a difference in the primary outcome of escalation in therapy in patients <40 kg. A subgroup analysis of patients <40 kg (n = 149) found patients who received magnesium doses >27 mg/kg had a higher incidence of the primary outcome of escalation in therapy, 15 patients (18.3%) versus 3 patients (4.5%) in the ≤27-mg/kg/dose group (p = 0.011). CONCLUSIONS: Our results demonstrate larger doses of magnesium sulfate are associated with an increased need for invasive or non-invasive mechanical ventilation or need for adjunctive therapy(ies). Our findings are limited by confounding factors that may have influenced this outcome in our population.

Variety, the spice of life and essential for robustness in excitation energy transfer in light-harvesting complexes.

For over a decade there has been some significant excitement and speculation that quantum effects may be important in the excitation energy transport process in the light harvesting complexes of certain bacteria and algae, in particular via the Fenna-Matthews-Olsen (FMO) complex. Whilst the excitement may have waned somewhat with the realisation that the observed long-lived oscillations in two-dimensional electronic spectra of FMO are probably due to vibronic coherences, it remains a question whether these coherences may play any important role. We review our recent work showing how important the site-to-site variation in coupling between chloroplasts in FMO and their protein scaffold environment is for energy transport in FMO and investigate the role of vibronic modes in this transport. Whilst the effects of vibronic excitations seem modest for FMO, we show that for bilin-based pigment-protein complexes of marine algae, in particular PC645, the site-dependent vibronic excitations seem essential for robust excitation energy transport, which may again open the door for important quantum effects to be important in these photosynthetic complexes.

Arctic closure as a trigger for Atlantic overturning at the Eocene-Oligocene Transition.

The Eocene-Oligocene Transition (EOT), approximately 34 Ma ago, marks a period of major global cooling and inception of the Antarctic ice sheet. Proxies of deep circulation suggest a contemporaneous onset or strengthening of the Atlantic meridional overturning circulation (AMOC). Proxy evidence of gradual salinification of the North Atlantic and tectonically driven isolation of the Arctic suggest that closing the Arctic-Atlantic gateway could have triggered the AMOC at the EOT. We demonstrate this trigger of the AMOC using a new paleoclimate model with late Eocene boundary conditions. The control simulation reproduces Eocene observations of low Arctic salinities. Subsequent closure of the Arctic-Atlantic gateway triggers the AMOC by blocking freshwater inflow from the Arctic. Salt advection feedbacks then lead to cessation of overturning in the North Pacific. These circulation changes imply major warming of the North Atlantic Ocean, and simultaneous cooling of the North Pacific, but no interhemispheric change in temperatures.