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We prove a universality result that reduces the free energy of rank-one matrix estimation problems in the setting of mismatched prior and noise to the computation of the free energy for a modified Sherrington–Kirkpatrick spin glass. Our main result is an almost sure large deviation principle for the overlaps between the true signal and the estimator for both the Bayes-optimal and mismatched settings. Through the large deviations principle, we recover the limit of the free energy in mismatched inference problems and the universality of the overlaps. [ABSTRACT FROM AUTHOR]

Introduction: While living donor liver transplantation (LDLT) serves as the predominant method of adult liver transplant (LT) in the Republic of Korea (ROK), it represents a minority of LT in the United States (US). A survey was conducted to gain insight into these nations' anesthetic management. Methods: An electronic questionnaire was distributed to directors of LT anesthesiology overseeing LDLT programs in both countries between May 2021 and October 2021. Results: The response rate was 93.0% (100% [37/37] in the US and 80% [16/20] in the ROK). Both countries mainly adhered to deceased donor LT recipient management practices, including the frequency of routine pulmonary artery catheter use, transesophageal echocardiography, and point‐of‐care coagulation monitoring. Differences were observed in early extubation of recipients (US vs. ROK: 39.7% vs. 14.7% of all cases), participation in donor selection meetings (88.9% [32/36] vs. 6.3% [1/16], p < 0.0001), application of the Enhanced Recovery After Surgery donor protocol (69.4% [25/36] vs. 12.5% [2/16], p < 0.0001), and cell saver usage for donors (94.4% [34/36] vs. 18.8% [3/16], p < 0.0001). More ROK programs implemented simultaneous donor/recipient anesthesia supervision by a single anesthesiologist. Conclusions: Several important differences were identified between the US and the ROK in adult LDLT anesthetic management. [ABSTRACT FROM AUTHOR]

The Huatung Basin (HB), situated on the leading part of the Philippine Sea Plate, is directly involved in oblique subduction and mountain building in the Taiwan region. However, previous studies have reported a wide range of ages for the HB, from 30 to 130 Ma, making it difficult to properly constrain regional tectonics. We analyzed teleseismic waveforms recorded on Taiwan that traveled through the slab associated with the HB. By waveform matching, we have constrained the slab dimensions to approximately 400 km in length and 150 km in width, accompanied by an enhanced P-wave velocity of 6% within the slab core and an apparent dip angle of 55°. We used age-dependent subduction zone thermal models to estimate the thermal ages or the ages since the last thermal event of the HB. The best-fit thermal model indicates thermal ages ranging from 20 to 50 Ma, which is consistent with a suite of geophysical observations and the age inferred from geomagnetic anomaly data. However, our results differ considerably from the ages obtained through radiometric dating of rocks dredged from the seafloor. The discrepancy in age may be attributed to either thermal rejuvenation of the plate or dating of allochthonous samples dredged from the border of the basin. [ABSTRACT FROM AUTHOR]

The Huatung Basin (HB), situated on the leading part of the Philippine Sea Plate, is directly involved in oblique subduction and mountain building in the Taiwan region. However, previous studies have reported a wide range of ages for the HB, from 30 to 130 Ma, making it difficult to properly constrain regional tectonics. We analyzed teleseismic waveforms recorded on Taiwan that traveled through the slab associated with the HB. By waveform matching, we have constrained the slab dimensions to approximately 400 km in length and 150 km in width, accompanied by an enhanced P-wave velocity of 6% within the slab core and an apparent dip angle of 55°. We used age-dependent subduction zone thermal models to estimate the thermal ages or the ages since the last thermal event of the HB. The best-fit thermal model indicates thermal ages ranging from 20 to 50 Ma, which is consistent with a suite of geophysical observations and the age inferred from geomagnetic anomaly data. However, our results differ considerably from the ages obtained through radiometric dating of rocks dredged from the seafloor. The discrepancy in age may be attributed to either thermal rejuvenation of the plate or dating of allochthonous samples dredged from the border of the basin. [ABSTRACT FROM AUTHOR]

Interscalene brachial plexus block (ISBPB) provides optimal analgesia for shoulder surgery. However, several limitations still exist, including the short duration of analgesia, rebound pain, a high incidence of unilateral diaphragmatic paresis, and potential risk of nerve damage, prompting the search for alternative techniques. Many alternatives to ISBPB have been studied to alleviate these concerns, and clinicians should choose an appropriate option based on the patient’s condition. In this mini-review, we aimed to present recent updates on ISBPB while discussing our clinical experiences in shoulder surgery. [ABSTRACT FROM AUTHOR]

To determine if single-injection bilateral posterior quadratus lumborum block (QLB) with ropivacaine would improve postoperative analgesia in the first 24 h after laparoscopic hepatectomy, compared with 0.9% saline. Prospective, double blinded, randomized controlled trial. A single tertiary care center from November 2021 and January 2023. A total of 94 patients scheduled to undergo laparoscopic hepatectomy due to hepatocellular carcinoma. Ninety-four patients were randomized into a QLB group (receiving 20 mL of 0.375% ropivacaine on each side, 150 mg in total) or a control group (receiving 20 mL of 0.9% saline on each side). The primary outcome was the cumulative opioid consumption during the initial 24-h post-surgery. Secondary outcomes included pain scores and intraoperative and recovery parameters. The mean cumulative opioid consumption during the initial 24-h post-surgery was 30.8 ± 22.4 mg in the QLB group (n = 46) and 34.0 ± 19.4 mg in the control group (n = 46, mean differences: −3.3 mg, 95% confidence interval, −11.9 to 5.4, p = 0.457). The mean resting pain score at 1 h post-surgery was significantly lower in the QLB group than in the control group (5 [4–6.25] vs. 7 [4.75–8], p = 0.035). No significant intergroup differences were observed in the resting or coughing pain scores at other time points or in other secondary outcomes. Preoperative bilateral posterior QLB did not reduce cumulative opioid consumption during the first 24 h after laparoscopic hepatectomy. • Posterior QLB didn't reduce postoperative opioid dose in laparoscopic hepatectomy. • Posterior QLB and control groups showed comparable recovery outcomes. • Need for further studies focusing on optimizing the timing and dosage of QLB. [ABSTRACT FROM AUTHOR]

Living donor liver transplantation was first developed to mitigate the limited access to deceased donor organs in Asia in the 1990s. This alternative liver transplantation method has become a widely practiced and established transplantation option for adult patients suffering with end‐stage liver disease, and it has successfully helped address the shortage of deceased donors. The Society for the Advancement of Transplant Anesthesia and the Korean Society of Transplantation Anesthesiologists jointly reviewed published studies on the perioperative management of adult live liver donors undergoing donor hemi‐hepatectomy. The goal of the review is to offer transplant anesthesiologists and critical care physicians a comprehensive overview of the perioperative management of adult live donors. We featured the current status, donor selection process, outcomes and complications, surgical procedure, anesthetic management, Enhanced Recovery After Surgery protocols, avoidance of blood transfusion, and considerations for emergency donation. Recent surgical advances, including laparoscopic donor hemi‐hepatectomy and robotic laparoscopic donor surgery, are also addressed. [ABSTRACT FROM AUTHOR]

Living donor liver transplantation was first developed to mitigate the limited access to deceased donor organs in Asia in the 1990s. This alternative liver transplantation option has become an established and widely practiced transplantation method for adult patients suffering from end‐stage liver disease. It has successfully addressed the shortage of deceased donors. The Society for the Advancement of Transplant Anesthesia and the Korean Society of Transplant Anesthesia jointly reviewed published studies on the perioperative management of live donor liver transplant recipients. The review aims to offer transplant anesthesiologists and critical care physicians a comprehensive overview of the perioperative management of adult live liver transplantation recipients. We feature the status, outcomes, surgical procedure, portal venous decompression, anesthetic management, prevention of acute kidney injury, avoidance of blood transfusion, monitoring and therapeutic strategies of hemodynamic derangements, and Enhanced Recovery After Surgery protocols for liver transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Although surgical competency and anesthesia for liver transplantation (LT) have evolved significantly in the past decades, intraoperative cardiac arrest (ICA) is still an event that brings a poor prognosis to the recipient. We report a second‐decade experience of ICA as a follow‐up study of our first report at our institution. Methods: This is a retrospective observational study of the medical records and the Liver Transplant Program database of our institution. LT from January 2011 to June 2023 were included. Of the 1735 LT cases, a total of 1730 cases were included, excluding three non‐Asian and two simultaneous heart and liver transplants (1598 adult LT, 132 pediatric LT). Results: The ICA incidence during adult LT was 0.7% (11/1598) which is significantly lower compared to our first report (1.5%; 14/919) (p = 0.042). ICA occurred only in adult recipients. Post‐reperfusion syndrome (PRS, six cases) and bleeding (four cases) were the primary causes in most cases and most ICA occurred after reperfusion (10/11). The mortality rates within 24 h, 30 days, and 1 year were 27.3%, 45.5%, and 54.5%, respectively. The survival curve did not show a significant difference from our first report (p = 0.570), and the survival rate of the ICA group was significantly lower compared to the non‐ICA group. (p = 0.000) Conclusion: The incidence of ICA has decreased, but the main causes of ICA as PRS and bleeding after reperfusion have not changed. Additionally, there was no significant difference in the survival curves from the first report. Because ICA is still fatal, efforts to reduce its incidence should be continued. [ABSTRACT FROM AUTHOR]

Choline geranate deep eutectic solvent/ionic liquid (CAGE) has shown several desirable therapeutic properties including antimicrobial activity and ability to deliver drugs transdermally in research laboratories. Here, we describe the first report of clinical translation of CAGE from the lab into the clinic for the treatment of rosacea, a common chronic inflammatory skin disorder that affects the face. We describe the seven steps of clinical translation including (a) scale‐up, (b) characterization, (c) stability analysis, (d) mechanism of action, (e) dose determination, (f) GLP toxicity study, and (g) human clinical study. We describe the challenges and outcomes in these steps, especially those that uniquely arise from the deep eutectic nature of CAGE. Our translational efforts led to a 12‐week open‐label phase 1b cosmetic study with CAGE1:2 gel (CGB400) in mild–moderate facial rosacea in 26 patients where CGB400 exhibited a marked reduction in the number of inflammatory lesions. These results demonstrate the therapeutic potential of CGB400 for treating rosacea as well as it provides insights into the translational journey of deep eutectic solvents, in particular CAGE, for dermatological applications. [ABSTRACT FROM AUTHOR]

Biopsy-based histology has been the foundation of disease diagnosis and management for over a century. A long-sought goal in dermatology is the development of an imaging modality with sufficient resolution and compositional detail to noninvasively interrogate skin histology in vivo. Here, we describe a system that achieves this goal using cross-sectionally scanned, multimodal microscopy (cross-modal). Cross-modal combines multiphoton and reflectance confocal microscopy into one compact system with coordinated three-axis scanning that preserves optical resolution in cross-section. A custom pinhole-free mechanism employing finite-infinite conjugates further simplifies and stabilizes confocal alignment. Evaluated in participants ages 9–81 and Fitzpatrick skin types (FST) 1–5, cross-modal images revealed histological details analogous to those obtained from traditional biopsied tissue. We observed dermal elastosis in sun-damaged skin, elevated melanin in pigmented skin, basaloid nests in basal cell carcinoma, and elongated rete ridges in seborrheic keratosis, supporting cross-modal's potential to deliver histological insights noninvasively. [ABSTRACT FROM AUTHOR]

Cervical plexus blocks (CPBs) have been used in various head and neck surgeries to provide adequate anesthesia and/or analgesia; however, the block is performed in a narrow space in the region of the neck that contains many sensitive structures, multiple fascial layers, and complicated innervation. Since the intermediate CPB was introduced in addition to superficial and deep CPBs in 2004, there has been some confusion regarding the nomenclature and definition of CPBs, particularly the intermediate CPB. Additionally, as the role of ultrasound in the head and neck region has expanded, CPBs can be performed more safely and accurately under ultrasound guidance. In this review, the authors will describe the methods, including ultrasound-guided techniques, and clinical applications of conventional deep and superficial CPBs; in addition, the authors will discuss the controversial issues regarding intermediate CPBs, including nomenclature and associated potential adverse effects that may often be neglected, focusing on the anatomy of the cervical fascial layers and cervical plexus. Finally, the authors will attempt to refine the classification of CPB methods based on the target compartments, which can be easily identified under ultrasound guidance, with consideration of the effects of each method of CPB. [ABSTRACT FROM AUTHOR]

The morphologies of subducted remnants in the lower mantle are essential to our understanding of the history of plate tectonism. Here we image a high-velocity slab-like (HVSL) anomaly beneath the southeastern U.S. using waveforms from five deep earthquakes beneath South America recorded by the USArray. In addition to travel time anomalies, the multipathing of S and ScS phases at different distances are used to constrain the HVSL model. We jointly invert S and ScS traveltimes, amplitudes, and waveform complexities to produce a best fitting block model characterized by a rectangular shape with a 2.5% S wave velocity increase and tapered edges. While the Farallon slab is expected to dip primarily eastward, the HVSL structure apparently dips 40° to 50° to the SE and appears to be related to the eclogitized Hess conjugate. [ABSTRACT FROM AUTHOR]

The lowermost 100–300 km of the Earth's mantle commonly regarded as the thermal boundary layer (TBL) of mantle circulation is characterized by its complex physical properties. Beneath the Caribbean this so-called D ″ layer features relatively high velocities and abrupt impedance increase at the top (designated as the D ″ discontinuity). These seismic characteristics have been attributed to the accumulation of ancient subducted slab material and the phase transition in the major lower mantle mineral of pervoskite. Geodynamic models predict that the blanketing cold slabs may trap enough heat from core to be buoyantly destabilized, and eventually broken apart and entrained into the bottom of the convection cell. Here we explore the D ″ structure with unprecedented resolution through modeling traveltimes, amplitudes, and waveform shapes from the USArray. We find an east-to-west asymmetrical undulation of the D ″ discontinuity with a V-shaped depression of ∼70–160 km over a lateral distance of 600 km beneath northern South America. The shear velocity perturbations vary in the same trend showing the most pronounced reduction of ∼3–4% below the thinnest D ″ layer in close proximity to an intermittently undetected discontinuity. The strong correlation between the D ″ topography and velocity variations indicates the phase transition boundary has been perturbed or even disrupted by the large lateral temperature gradient of slab material which has been reheated from the core over extended periods of time. [ABSTRACT FROM AUTHOR]

The Lithosphere–Asthenosphere Boundary (LAB), where a layer of low viscosity asthenosphere decouples with the upper plate motion, plays an essential role in plate tectonics. Most dynamic modeling assumes that the shear velocity can be used as a surrogate for viscosity which provides key information about mantle flow. Here, we derive a shear velocity model for the LAB structure beneath the Gulf of Mexico allowing a detailed comparison with that beneath the Pacific (PAC) and Atlantic (ATL). Our study takes advantage of the USArray data from the March 25th, 2013 Guatemala earthquake at a depth of 200 km. Such data is unique in that we can observe a direct upward traveling lid arrival which remains the first arrival ahead of the triplications beyond 18°. This extra feature in conjunction with upper-mantle triplication sampling allows good depth control of the LAB and a new upper-mantle seismic model ATM, a modification of ATL, to be developed. ATM has a prominent low velocity zone similar to the structure beneath the western Atlantic. The model contains strong radial anisotropy in the lid where V SH is about 6% faster than V SV . This anisotropic feature ends at the bottom of the lithosphere at about the depth of 175 km in contrast to the Pacific where it extends to over 300 km. Another important feature of ATM is the weaker velocity gradient from the depth of 175 to 350 km compared to Pacific models, which may be related to differences in mantle flow. [ABSTRACT FROM AUTHOR]

Mechanosensory fibers are enveloped by myelin, a unique multilamellar membrane permitting saltatory neuronal conduction. Damage to myelin is thought to contribute to severe pain evoked by innocuous tactile stimulation (i.e., mechanical allodynia). Our earlier (Liu et al., 2012) and present data demonstrate that a single injection of a myelin basic protein-derived peptide (MBP84-104) into an intact sciatic nerve produces a robust and long-lasting (>30 days) mechanical allodynia in female rats. The MBP84-104 peptide represents the immunodominant epitope and requires T cells to maintain allodynia. Surprisingly, only systemic gabapentin (a ligand of voltage-gated calcium channel α2δ1), but not ketorolac (COX inhibitor), lidocaine (sodium channel blocker) or MK801 (NMDA antagonist) reverse allodynia induced by the intrasciatic MBP84-104. The genome-wide transcriptional profiling of the sciatic nerve followed by the bioinformatics analyses of the expression changes identified interleukin (IL)-6 as the major cytokine induced by MBP84-104 in both the control and athymic T cell-deficient nude rats. The intrasciatic MBP84-104 injection resulted in both unilateral allodynia and unilateral IL-6 increase the segmental spinal cord (neurons and astrocytes). An intrathecal delivery of a function-blocking IL-6 antibody reduced the allodynia in part by the transcriptional effects in large-diameter primary afferents in DRG. Our data suggest that MBP regulates IL-6 expression in the nervous system and that the spinal IL-6 activity mediates nociceptive processing stimulated by the MBP epitopes released after damage or disease of the somatosensory nervous system. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury. Methods: This 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) via arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury. Results: Thirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, P = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, P = 0.022), lower prothrombin time (OR 0.01, P = 0.025), and greater total cholesterol level (OR 1.04, P = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, P = 0.014; alanine transaminase, β 81.6, standard error 38.1, P = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations. Conclusions: Hyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: We quantified the dose-sparing effect of epinephrine by comparing the median effective dose (ED) of intrathecal hyperbaric bupivacaine co-administered with epinephrine with the ED of intrathecal hyperbaric bupivacaine alone. Methods: Three groups were randomly generated from 162 patients undergoing total knee replacement arthroplasty under combined spinal and epidural anesthesia: Group B (bupivacaine), Group BE1 (bupivacaine plus epinephrine 100 μg), and Group BE2 (bupivacaine plus epinephrine 200 μg). Each group was further divided by bupivacaine doses of 6, 7, 8, 9, 10, or 11 mg. The anesthesia was defined as successful if a bilateral T12 sensory block occurred within 15 min, and no intraoperative epidural supplement was required. The ED and ED for successful anesthesia and successful tourniquet pain blockade were determined separately by probit regression analysis. Results: The ED and ED of intrathecal hyperbaric bupivacaine for successful anesthesia were not different among the groups: the ED values were 7.1 mg [95 % confidence interval (95 % CI) 6.0-8.0 mg] in Group B, 6.2 mg (95 % CI 4.8-7.2 mg) in Group BE1, and 6.3 mg (95 % CI 4.9-7.2 mg) in Group BE2. However, the ED and ED values for tourniquet pain control were significantly smaller in Groups BE1 and BE2 than in Group B: the ED values were 7.2 mg (95 % CI 6.3-7.9 mg), 5.5 mg (95 % CI 4.1-6.3 mg), and 5.3 mg (95 % CI 3.7-6.2 mg) in Groups B, BE1, and BE2, respectively. The incidence of tourniquet pain was significantly lower in Groups BE1 and BE2 than in Group B. The time to patients' requests for supplemental analgesia was significantly longer in Groups BE1 and BE2 than in Group B. Conclusions: Intrathecal epinephrine did not decrease the dose of intrathecal hyperbaric bupivacaine required for successful anesthesia. However, it reduced the dose required for tourniquet pain blockade. [ABSTRACT FROM AUTHOR]

Abstract: Background: The effect of opioids on inflammation and immune responses is an important subject of investigation because immunoregulatory cytokines are produced in the central nervous system and opioid receptors are widespread in these cells. Objectives: The aim of this study was to evaluate the immunomodulatory effect of morphine on the C3 expression (both constitutive and proinflammatory cytokine-induced C3 expression) in primary rat astrocytes. Methods: Primary rat astrocytes were untreated or treated with morphine in different concentrations (10–6 to 10–2 M) before incubation without or with 5 U/mL tumor necrosis factor-α (TNF-α), and C3 protein and mRNA expressions were measured. Similarly, astrocytes were treated with 10–3 M morphine and stimulated with other proinflammatory cytokines, including 10 ng/mL interleukin-8 (IL-8) and 5 U/mL IL-1β. Astrocytes were exposed to 10–5 M naloxone for 2 hours before adding morphine, and TNF-α and C3 protein was measured. Tumor growth factor-β (TGF-β) was measured from the supernatants of each proinflammatory cytokine. Results: All results are expressed as mean percentages of C3 production by normalizing C3 without morphine or any cytokine treatment as 100%. Constitutive C3 protein production was decreased at morphine 10–3 M (57.2%) and 10–2 M (30.1%). Pretreatment with morphine suppressed induction of C3 expression at both the protein and mRNA levels in astrocytes stimulated with TNF-α, IL-8, and IL-1β (P < 0.05) in a dose-dependent manner. The inhibition of C3 protein production by morphine (10–3 M; 33%) was partially attenuated by naloxone (52.0%) (P < 0.05). The pretreatment of astrocytes with morphine (10–3 M) before stimulation with TNF-α, IL-8, and IL-1β increased by 33% (P < 0.05), decreased by 15.2% (P < 0.05), and did not change the production of TGF-β protein, respectively. Conclusions: Morphine downregulated both constitutive and proinflammatory cytokine-induced C3 expression of astrocytes at the transcriptional level, but not in a cytokine-specific manner. [Copyright &y& Elsevier]

We compared postoperative hepatic and renal functions between the two inhalational anesthetics, desflurane and sevoflurane in living donors undergoing right hepatectomy. Seventy-four adult donors were randomly allocated into Des group ( n = 37) and sevo group ( n = 37). Before the induction of anesthesia, morphine sulfate 400 μg was injected intrathecally. Anesthesia was maintained with one minimum alveolar concentration (MAC) of deflurane or sevoflurane plus continuous intravenous remifentanil. Liver and renal function tests were performed and analysed at preoperative period, immediately after operation, and on 1st, 2nd, 3rd, 5th, 7th, and 30th postoperative days (PODs). Aspartate aminotransferase (AST) showed significant elevations from the day of surgery to POD 3 and alanine aminotransferase (ALT) was significantly elevated on POD 1 and POD 3 in the sevo group. Albumin level was significantly lower on POD 2 in the sevo group. Creatinine was significantly higher on POD 3 and POD 30 and estimated glomerular filtration ratio was significantly lower on POD 3 and POD 30 in the sevo group. No patient developed hepatic or renal failures. The results of our study showed better postoperative hepatic and renal function test with desflurane than sevoflurane at equivalent dose of 1 MAC in living donors undergoing right hepatectomy, but further study is required to evaluate clinical importance. [ABSTRACT FROM AUTHOR]

Background: There are reports of rare adverse effects of tumor necrosis factor (TNF) inhibitors, including infections, malignancies, and induction of autoimmune conditions. Intriguing, are cases of induction or exacerbation of psoriasis in conjunction with TNF inhibitor therapy, given that they are approved for treatment of the same condition. Objective: Published cases of psoriasis occurring during anti-TNF therapy were analyzed, including overviews of proposed etiologies and treatment recommendations. Methods: A literature search using Ovid MEDLINE and PubMed was performed for articles published between January 1990 and September 2007 to collect reported cases of psoriasis in patients receiving therapy with TNF blocking agents. Results: A total of 127 cases were identified: 70 in patients on infliximab (55.1%), 35 with etanercept (27.6%), and 22 with adalimumab (17.3%). Females comprised 58% of cases; mean age of reported patients was 45.8 years, and the time from initiation of treatment to onset of lesions averaged 10.5 months. These patients suffered from a number of primary conditions, with rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease accounting for the vast majority. Palmoplantar pustular psoriasis was observed in 40.5% of the cases, with plaque-type psoriasis in 33.1%, and other types comprising the remainder. Topical corticosteroids were the most commonly employed treatment modality but led to resolution in only 26.8% of cases in which they were employed solely. Switching to a different anti-TNF agent led to resolution in 15.4% of cases. Cessation of anti-TNF therapy with systemic therapy led to resolution in 64.3% of cases. Conclusion: More information and cases are needed. Biopsies of TNF-blockade-induced lesions may reveal what cytokines and cell types drive the development of these lesions. Additionally, there is a need to develop an algorithm to treat this paradoxical side effect of therapy with TNF-blockers. [ABSTRACT FROM AUTHOR]

Decompensated cirrhotic patients experience severely increased intestinal permeability and bacterial translocation. Thus, autologous blood salvaged during deceased donor liver transplantation (DDLT) may be contaminated with enteric bacteria. We aimed to evaluate bacterial contamination of autologous blood salvaged during DDLT and its association with post-transplant bacteremia. In 30 patients undergoing DDLT, bacterial culture was performed in salvaged autologous blood samples: one before graft reperfusion (non-leukoreduced) and two after graft reperfusion (non-leukoreduced and leukoreduced). The primary outcome was bacterial contamination of salvaged autologous blood. Seven of 30 patients (23.3%) were positive for bacteria (3 enteric/4 non-enteric) before graft reperfusion while 11 patients (36.7%) were positive (5 enteric/6 non-enteric) after graft reperfusion. Six of 7 patients who were positive for bacteria before graft reperfusion were positive after graft reperfusion with the same bacteria. Only 4 of 11 contaminated blood samples were converted to negative after leukoreduction. Post-transplant bacteremia risk was insignificantly greater in patients who received autologous blood with bacteria than in patients without bacteria (30.0% vs. 5.0%, P = 0.06). We found contamination of salvaged autologous blood with enteric bacteria throughout DDLT and incomplete performance of leukoreduction, indicating high bacterial load. The potential association between contaminated autotransfusion and post-transplant bacteremia warrants further validation in a larger prospective study. Clinical trial notation: This study was registered at the Clinical Research Information Service (CRiS; https://cris.nih.go.kr; No. KCT0007223; principal registration investigator: Sangbin Han, date of registration: April 25, 2022). [ABSTRACT FROM AUTHOR]

Background: The Portland intensive insulin therapy effectively controls acute hyperglycemic change after graft reperfusion during liver transplantation. However, the time-consuming sophistication acts as a barrier leading to misinterpretation and decreasing compliance to the protocol; thus, we newly introduced an application software “Insulin protocol calculator” which automatically calculates therapeutic bolus/continuous insulin doses based on the Portland protocol. Methods: Of 144 patients who underwent liver transplantation, 74 patients were treated before the introduction of “Insulin protocol calculator” by using a paper manual, and 70 patients were treated by using the application. Compliance was defined as the proportion of patients treated with exact bolus/continuous insulin dose according to the Portland protocol. Results: Compliance was significantly greater in app group than in paper group regarding bolus dose (94.5% and 86.9%, P < 0.001), continuous dose (88.9% and 77.3%, P = 0.001), and both doses (86.6% and 73.8%, P < 0.001). Blood glucose concentration was significantly lower in app group at 3 h (125 ± 17 mg/dl vs. 136 ± 19 mg/dl, P = 0.014) and 4 h (135 ± 22 mg/dl vs. 115 ± 15 mg/dl, P = 0.029) after graft reperfusion. Acute hyperglycemic change during 30 min was more prominent in app group while hyperglycemia incidence was 71.4% vs. 54.1% (P = 0.031). However, hyperglycemia risk was comparable at 2 h (31.4% vs. 31.1%, P = 0.964), and even insignificantly lower in app group at 3 h (7.1% vs. 19.5%, P = 0.184). Conclusions: Compliance to the Portland protocol was significantly improved after introducing the application software; post-reperfusion hyperglycemia was better controlled. “Insulin protocol calculator” is cost-effective and time-saving with potential clinical benefits. [ABSTRACT FROM AUTHOR]

Understanding the origin of structures in the lower mantle and D" in particular is key to understanding how the Earth works as a global interconnected system. The role of subducted slabs involving the Circum-Pacific lower mantle high velocity belt proves particularly complicated with a mixture of phase-changes and up-welling zones. Here, we address such a complicated structure beneath South America by exploiting diffracted S-waveforms from a deep event beneath the South Sandwich Islands recorded by USArray. The upper mantle effects are removed by using a calibrated procedure provided by closer events. Our modeling results display a NS linear feature separating a fast slab and a prominent low-velocity lumpy strip, about 250km wide, and over 1,000km long. The pile-like structure in cross-section is 50km high with a 2.5% decrease at the top and 5% decrease at the CMB. This is overlaid by a normal PPV structure. Such features are quite compatible with a weak iron-oxide mixture bulldozed by a sinking slab as suggested in some recent tomographic models. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine has sympatholytic effects. We investigated whether dexmedetomidine could attenuate stress responses in patients undergoing endoscopic transnasal transseptal transsphenoidal surgery. Methods: Forty-six patients were randomized to receive a continuous infusion of 0.9% saline (n = 23) or dexmedetomidine (n = 23). Immediately after general anesthesia induction, the dexmedetomidine group received a loading dose of 1 mcg/kg dexmedetomidine over 10 min, followed by a maintenance dose of 0.2–0.7 mcg/kg/h and the control group received 0.9% saline at the same volume until 30 min before the end of surgery. Serum levels of epinephrine, norepinephrine, and glucose were assessed before surgery (T1) and the end of drug infusion (T2). The primary outcome was the change in norepinephrine levels between the two time points. Results: Changes (T2-T1 values) in perioperative serum norepinephrine levels were significantly greater in the dexmedetomidine group than in the control group (median difference, 56.9 pg/dL; 95% confidence interval, 20.7 to 83.8 pg/dL; P = 0.002). However, epinephrine level changes did not show significant intergroup differences (P = 0.208). Significantly fewer patients in the dexmedetomidine group than in the control group required rescue analgesics at the recovery area (4.3% vs. 30.4%, P = 0.047). Conclusions: Intraoperative dexmedetomidine administration reduced norepinephrine release and rescue analgesic requirement. Dexmedetomidine might be used as an anesthetic adjuvant in patients undergoing transnasal transseptal transsphenoidal surgery. Trial registration: Clinical Trial Registry of Korea, identifier: KCT0003366; registration date: 21/11/2018; presenting author: Ji Seon Jeong. [ABSTRACT FROM AUTHOR]

Summary: Despite technical difficulties, right lobe liver grafting is preferred in living donor liver transplantation because of the graft size. Re‐exploration after living donor right lobe liver transplantation (LRLT) has never been separately analyzed. We aimed to analyze the incidence, causes, outcomes, and risk factors of re‐exploration after LRLT. We reviewed medical records of 1016 LRLT recipients from October 2003 to July 2017 and identified recipients who underwent re‐exploration within hospital stay. Separate analyses were also performed according to cause of re‐exploration. The overall incidence of re‐exploration was 17.0% (173/1016). The most common cause of re‐exploration was bleeding (50%). Overall re‐exploration was associated with clinical outcome, but different results were shown on analyses according to cause of re‐exploration. Risk factors of re‐exploration were underlying hepatocellular carcinoma and operative duration [Odds ratio (OR), 1.49; 95% confidence interval (CI), 1.05–2.12; P = 0.03, and OR, 1.002; 95% CI, 1.001–1.004; P = 0.0023, respectively]. Re‐exploration after LRLT is relatively common, and is strongly associated with mortality and graft failure. [ABSTRACT FROM AUTHOR]

Introduction: Ritlecitinib demonstrated efficacy in patients with alopecia areata (AA) in the ALLEGRO phase 2b/3 study (NCT03732807). However, hair loss presentation may vary based on location (e.g., scalp, eyebrow/eyelash, body). Here, we sought to identify distinct hair loss profiles at baseline and evaluate whether they affected the efficacy of ritlecitinib. Methods: Patients with AA aged ≥ 12 years with ≥ 50% scalp hair loss were randomized to daily ritlecitinib 10 mg (assessed for dose ranging only), 30 or 50 mg (± 4-week, 200-mg loading dose), or placebo for 24 weeks. Latent class analysis (LCA) identified hair loss profiles based on four baseline measurements: clinician-reported extent of scalp (Severity of Alopecia Tool score), eyebrow hair loss, eyelash hair loss, and patient-reported body hair loss. Logistic regression evaluated ritlecitinib (50 and 30 mg) efficacy vs placebo using Patient Global Impression of Change (PGI-C) and Patient Satisfaction with Hair Growth (P-Sat; amount, quality, and overall satisfaction) responses at Week 24, adjusting for key covariates, including latent class membership. Results: LCA identified five latent classes: (1) primarily non–alopecia totalis (AT; complete loss of scalp hair); (2) non-AT with moderate non-scalp involvement; (3) extensive scalp, eyebrow, and eyelash involvement; (4) AT with moderate non-scalp involvement; and (5) primarily alopecia universalis (complete scalp, face, and body hair loss). Adjusting for latent class membership, patients receiving ritlecitinib 30 or 50 mg were significantly more likely to achieve PGI-C response (30 mg: odds ratio, 8.62 [95% confidence interval, 4.42–18.08]; 50 mg: 12.29 [6.29–25.85]) and P-Sat quality of hair regrowth (30 mg: 6.71 [3.53–13.51]; 50 mg: 8.17 [4.30–16.46]) vs placebo at Week 24. Results were similar for P-Sat overall satisfaction and amount of hair regrowth. Conclusion: Distinct and clinically relevant hair loss profiles were identified in ALLEGRO-2b/3 participants. Ritlecitinib was efficacious compared with placebo, independent of hair loss profile at baseline. Trial registration: ClinicalTrials.gov identifier, NCT03732807. [ABSTRACT FROM AUTHOR]

The use of a minimally invasive laparoscopic approach in living donor hepatectomy is increasing with the need for enhanced management of living donors. Hypotensive bradycardia often occurs during abdominal surgery and can be fatal without proper management. We conducted a retrospective study to investigate the incidence and risk factors of symptomatic (hypotensive) bradycardia in laparoscopic living donor hepatectomy. Hypotensive bradycardia is defined as the heart rate below 60 beats per minute with simultaneous mean arterial blood pressure (MAP) below 65 mm Hg. Clinical characteristics of liver donors were collected and analyzed from May 2018 to July 2019. This study included 129 cases of living donor hepatectomy; 11 donors of open hepatectomy were excluded, and 118 donors undergoing laparoscopic hepatectomy were analyzed. Hypotensive bradycardia was shown in 27 donors. Hypertension or angiotensin receptor blocker medication were significantly related to hypotensive bradycardia. Hypotensive bradycardia occurred after incision in 22 donors, and the onset time from the incision was 7.5 minutes [first quartile (Q1) 5.75, third quartile (Q3) 11.5, range 0-25], the minimum heart rate was 48.5 beats per minute (Q1 41.5, Q3 53.25, range 25-57), and the minimum MAP was 55 mm Hg (Q1 45, Q3 57.5, range 35-63). It took 132 seconds (Q1 42, Q3 189, range 12-408) to recover MAP over 65 mm Hg. Hypotensive bradycardia occurred in 22.9% of the laparoscopic living donor hepatectomy cases, and 80.6% of cases occurred after incision. Thorough preoperative evaluation and close monitoring is important even in a healthy donor. • The use of laparoscopic living donor hepatectomy is increasing and has various benefits; however, intraoperative symptomatic (hypotensive) bradycardia occurs in more than one-fourth of cases. • In the living donor population, hypertension or angiotensin receptor blocker medication is related to hypotensive bradycardia. • Prompt treatment and discussion with a surgeon is required when hypotensive bradycardia occurs during laparoscopic living donor hepatectomy. [ABSTRACT FROM AUTHOR]

Background: Compared with open surgery, laparoscopic liver resection is a minimally invasive surgical technique. However, a number of patients experience moderate-to-severe postoperative pain after laparoscopic liver resection. This study aims to compare the postoperative analgesic effects of erector spinae plane block (ESPB) and quadratus lumborum block (QLB) in patients undergoing laparoscopic liver resection. Methods: One hundred and fourteen patients undergoing laparoscopic liver resection will be randomly allocated to three groups (control, ESPB, or QLB) in a 1:1:1 ratio. In the control group, participants will receive systemic analgesia consisting of regular NSAIDs and fentanyl-based patient-controlled analgesia (PCA) according to the institutional postoperative analgesia protocol. In the two experimental groups (ESPB or QLB group), the participants will receive preoperative bilateral ESPB or bilateral QLB in addition to systemic analgesia according to the institutional protocol. ESPB will be performed at the 8th thoracic vertebra level with ultrasound guidance before surgery. QLB will be performed in the supine position on the posterior plane of the quadratus lumborum with ultrasound guidance before surgery. The primary outcome is cumulative opioid consumption 24 h after surgery. Secondary outcomes are cumulative opioid consumption, pain severity, opioid-related adverse events, and block-related adverse events at predetermined time points (24, 48, and 72 h after surgery). Differences in plasma ropivacaine concentrations in the ESPB and QLB groups would be investigated, and the quality of postoperative recovery among the groups will be compared. Discussion: This study will reveal the usefulness of ESPB and QLB in terms of postoperative analgesic efficacy and safety in patients undergoing laparoscopic liver resection. Additionally, the study results will provide information on the analgesic superiority of ESPB versus QLB in the same population. Trial registration: Prospectively registered with the Clinical Research Information Service on August 3, 2022; KCT0007599. [ABSTRACT FROM AUTHOR]

Background: Compared with open surgery, laparoscopic liver resection is a minimally invasive surgical technique. However, a number of patients experience moderate-to-severe postoperative pain after laparoscopic liver resection. This study aims to compare the postoperative analgesic effects of erector spinae plane block (ESPB) and quadratus lumborum block (QLB) in patients undergoing laparoscopic liver resection. Methods: One hundred and fourteen patients undergoing laparoscopic liver resection will be randomly allocated to three groups (control, ESPB, or QLB) in a 1:1:1 ratio. In the control group, participants will receive systemic analgesia consisting of regular NSAIDs and fentanyl-based patient-controlled analgesia (PCA) according to the institutional postoperative analgesia protocol. In the two experimental groups (ESPB or QLB group), the participants will receive preoperative bilateral ESPB or bilateral QLB in addition to systemic analgesia according to the institutional protocol. ESPB will be performed at the 8th thoracic vertebra level with ultrasound guidance before surgery. QLB will be performed in the supine position on the posterior plane of the quadratus lumborum with ultrasound guidance before surgery. The primary outcome is cumulative opioid consumption 24 h after surgery. Secondary outcomes are cumulative opioid consumption, pain severity, opioid-related adverse events, and block-related adverse events at predetermined time points (24, 48, and 72 h after surgery). Differences in plasma ropivacaine concentrations in the ESPB and QLB groups would be investigated, and the quality of postoperative recovery among the groups will be compared. Discussion: This study will reveal the usefulness of ESPB and QLB in terms of postoperative analgesic efficacy and safety in patients undergoing laparoscopic liver resection. Additionally, the study results will provide information on the analgesic superiority of ESPB versus QLB in the same population. Trial registration: Prospectively registered with the Clinical Research Information Service on August 3, 2022; KCT0007599. [ABSTRACT FROM AUTHOR]

Greater graft-failure-risk of female-to-male liver transplantation (LT) is thought to be due to acute decrease in hepatic-estrogen-signaling. Our previous research found evidence that female hepatic-estrogen-signaling decreases after 40 years or with macrosteatosis. Thus, we hypothesized that inferiority of female-to-male LT changes according to donor-age and macrosteatosis. We stratified 780 recipients of grafts from living-donors into four subgroups by donor-age and macrosteatosis and compared graft-failure-risk between female-to-male LT and other LTs within each subgroup using Cox model. In recipients with ≤ 40 years non-macrosteatotic donors, graft-failure-risk was significantly greater in female-to-male LT than others (HR 2.03 [1.18–3.49], P = 0.011). Within the subgroup of recipients without hepatocellular carcinoma, the inferiority of female-to-male LT became greater (HR 4.75 [2.02–11.21], P < 0.001). Despite good graft quality, 1y-graft-failure-probability was 37.9% (23.1%–57.9%) in female-to-male LT within this subgroup while such exceptionally high probability was not shown in any other subgroups even with worse graft quality. When donor was > 40 years or macrosteatotic, graft-failure-risk was not significantly different between female-to-male LT and others (P > 0.60). These results were in agreement with the estrogen receptor immunohistochemistry evaluation of donor liver. In conclusion, we found that the inferiority of female-to-male LT was only found when donor was ≤ 40 years and non-macrosteatotic. Abrogation of the inferiority when donor was > 40 years or macrosteatotic suggests the presence of dominant contributors for post-transplant graft-failure other than graft quality/quantity and supports the role of hepatic-estrogen-signaling mismatch on graft-failure after female-to-male LT. [ABSTRACT FROM AUTHOR]

Background: Intrathecal morphine (ITM) injection is an effective postoperative analgesic strategy in open or laparoscopic donor hepatectomy; however, the optimal dose has not been determined. In this trial, we compared the post‐operative analgesic effects of two doses (300 vs. 400 μg) of ITM injections. Methods: In this prospective randomized non‐inferiority trial, 56 donors were divided into either the 300 μg or 400 μg ITM group (n = 28, each). The primary outcome was the resting pain score at 24 h postoperatively. Pain scores, cumulative opioid consumption, and side effects (postoperative nausea and vomiting [PONV]) were compared up to 48 h postoperatively. Results: Fifty‐five donors participated in the entire study. The mean resting pain scores at 24 h after surgery were 1.7 ± 1.6 and 1.7 ± 1.1 in the ITM 300 and ITM 400 groups, respectively (mean difference, 0 [95% CI, −.8 to.7], p =.978). The upper limit of the 95% CI was lower than the prespecified non‐inferiority margin (δ = 1), indicating that non‐inferiority had been established. The incidence of PONV was lower in the ITM 300 group than in the ITM 400 group at 18 (p =.035) and 24 h postoperatively (p =.015). There were no significant differences in the resting and coughing pain scores and cumulative opioid consumption at any time point. Conclusion: For laparoscopic donor hepatectomy, preoperative ITM 300 μg exhibited non‐inferior postoperative analgesic effects compared to ITM 400 μg, with a lower incidence of PONV. [ABSTRACT FROM AUTHOR]

Background: Compared with open surgery, laparoscopic liver resection is a minimally invasive surgical technique. However, a number of patients experience moderate-to-severe postoperative pain after laparoscopic liver resection. This study aims to compare the postoperative analgesic effects of erector spinae plane block (ESPB) and quadratus lumborum block (QLB) in patients undergoing laparoscopic liver resection. Methods: One hundred and fourteen patients undergoing laparoscopic liver resection will be randomly allocated to three groups (control, ESPB, or QLB) in a 1:1:1 ratio. In the control group, participants will receive systemic analgesia consisting of regular NSAIDs and fentanyl-based patient-controlled analgesia (PCA) according to the institutional postoperative analgesia protocol. In the two experimental groups (ESPB or QLB group), the participants will receive preoperative bilateral ESPB or bilateral QLB in addition to systemic analgesia according to the institutional protocol. ESPB will be performed at the 8th thoracic vertebra level with ultrasound guidance before surgery. QLB will be performed in the supine position on the posterior plane of the quadratus lumborum with ultrasound guidance before surgery. The primary outcome is cumulative opioid consumption 24 h after surgery. Secondary outcomes are cumulative opioid consumption, pain severity, opioid-related adverse events, and block-related adverse events at predetermined time points (24, 48, and 72 h after surgery). Differences in plasma ropivacaine concentrations in the ESPB and QLB groups would be investigated, and the quality of postoperative recovery among the groups will be compared. Discussion: This study will reveal the usefulness of ESPB and QLB in terms of postoperative analgesic efficacy and safety in patients undergoing laparoscopic liver resection. Additionally, the study results will provide information on the analgesic superiority of ESPB versus QLB in the same population. Trial registration: Prospectively registered with the Clinical Research Information Service on August 3, 2022; KCT0007599. [ABSTRACT FROM AUTHOR]

Background: Transfusion of allogeneic blood products can have adverse effects and profoundly influence postoperative liver transplantation outcomes, including graft survival. To minimize allogeneic red blood cell (RBC) transfusion, salvaged blood can be used during liver transplantation. The aim of this study was to determine the contribution of salvaged blood to allogeneic RBC transfusion in living donor liver transplantation (LDLT) recipients. Methods: Data of 311 adult-to-adult LDLT recipients between January 2015 and April 2019 were analyzed. The primary outcome was a change in requirement for allogeneic RBCs due to the use of salvaged blood. Additionally, predictors of intraoperative allogeneic RBC transfusion were investigated. Results: One hundred fifty-three (49.2%) recipients required allogeneic RBC transfusion. If recipients did not receive salvaged blood, 253 (81.4%) recipients would have needed allogeneic RBC transfusion. The total volume of salvaged blood transfused into recipients during surgery was 269,165 mL, which corresponded to 993 units of allogeneic RBCs and accounted for 76.1% of total RBC transfusion volume. Multivariate analysis showed that male recipients, model for end-stage liver disease score, preoperative hemoglobin level, and volume of salvaged blood used during surgery were independent predictors of the need for intraoperative allogenic RBC transfusion. Conclusions: Intraoperative use of salvaged blood significantly reduced allogeneic RBC transfusion in LDLT recipients. It can help transplant teams manage transfusion of allogeneic RBCs during liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Compared with open surgery, laparoscopic liver resection is a minimally invasive surgical technique. However, a number of patients experience moderate-to-severe postoperative pain after laparoscopic liver resection. This study aims to compare the postoperative analgesic effects of erector spinae plane block (ESPB) and quadratus lumborum block (QLB) in patients undergoing laparoscopic liver resection. Methods: One hundred and fourteen patients undergoing laparoscopic liver resection will be randomly allocated to three groups (control, ESPB, or QLB) in a 1:1:1 ratio. In the control group, participants will receive systemic analgesia consisting of regular NSAIDs and fentanyl-based patient-controlled analgesia (PCA) according to the institutional postoperative analgesia protocol. In the two experimental groups (ESPB or QLB group), the participants will receive preoperative bilateral ESPB or bilateral QLB in addition to systemic analgesia according to the institutional protocol. ESPB will be performed at the 8th thoracic vertebra level with ultrasound guidance before surgery. QLB will be performed in the supine position on the posterior plane of the quadratus lumborum with ultrasound guidance before surgery. The primary outcome is cumulative opioid consumption 24 h after surgery. Secondary outcomes are cumulative opioid consumption, pain severity, opioid-related adverse events, and block-related adverse events at predetermined time points (24, 48, and 72 h after surgery). Differences in plasma ropivacaine concentrations in the ESPB and QLB groups would be investigated, and the quality of postoperative recovery among the groups will be compared. Discussion: This study will reveal the usefulness of ESPB and QLB in terms of postoperative analgesic efficacy and safety in patients undergoing laparoscopic liver resection. Additionally, the study results will provide information on the analgesic superiority of ESPB versus QLB in the same population. Trial registration: Prospectively registered with the Clinical Research Information Service on August 3, 2022; KCT0007599. [ABSTRACT FROM AUTHOR]

Purpose: Traditionally, appropriate anchors are used to investigate the amount of change on a clinician-reported outcome assessment that is meaningful to individual patients. However, novel qualitative methods involving input from disease state experts together with patients may better inform the individual improvement threshold for demonstrating the clinical benefit of new treatments. This study aimed to establish a clinically meaningful threshold for treatment success for the clinician-reported Severity of Alopecia Tool (SALT) score for patients with alopecia areata (AA). Methods: A purposive sample of 10 dermatologists expert in AA and 30 adult and adolescent patients with AA and a history of ≥ 50% scalp hair loss were recruited. Semi-structured interview questions explored the outcome that represented treatment success to clinicians and patients. Findings were analyzed using thematic methods to identify treatment success thresholds. Results: Both informant groups confirmed scalp hair amount as the outcome of priority. Most expert clinicians considered a static threshold of 80% (n = 5) or 75% (n = 3) of the scalp hair as a treatment success. Most patient responses ranged from 70 to 90% (median: 80% of the scalp hair). Subsequently, queried patients confirmed that achieving SALT score ≤ 20 with treatment would be a success, as reflected in the Alopecia Areata Investigator Global Assessment (AA-IGA™). The novel qualitative processes used to inform this meaningful threshold reflects a clinician-then-patient process for: (a) confirmation of the patient outcome of priority; and (b) clinician input on a preliminary treatment success level for independent understanding among patients. Conclusion: This qualitative investigation of expert clinicians-then-patients with AA confirmed that achieving an amount of 80% or more scalp hair (SALT score ≤ 20) was an appropriate individual treatment success threshold indicating clinically meaningful improvement for patients with ≥ 50% scalp hair loss. A qualitative investigation of a quantifiable treatment success threshold is possible through a well-designed interview process with expert clinicians and the appropriate patient population. [ABSTRACT FROM AUTHOR]

Despite various intraoperative thermal strategies, core heat loss is considerable during liver transplantation and hypothermia is common. We tested whether forced-air prewarming prevents hypothermia during liver transplantation. Adult patients undergoing living donor liver transplantation were randomly assigned to non-prewarming group (n = 20) or prewarming group (n = 20). Patients in prewarming group underwent 30-min forced-air warming before anesthetic induction. During surgery, core temperature was measured in the pulmonary artery. The primary outcome was intraoperative hypothermia (< 36.0 °C). The secondary outcomes included plasma lactate concentration. Intraoperative hypothermia risk was significantly lower in prewarming group than in non-prewarming group (60.0% vs. 95.0%, P = 0.020). The difference in hypothermia incidence between groups was greater in the post-induction phase (20.0% vs. 85.0%, P < 0.001) than in the anhepatic or post-reperfusion phase, suggesting that prewarming mainly acts on preventing post-induction core-to-peripheral heat redistribution. Hypothermia duration was significantly shorter in prewarming group (60 [0–221] min vs. 383 [108–426] min, P = 0.001). Lactate concentration decreased during 3 h after graft reperfusion in prewarming group, whereas it continuously increased in non-prewarming group (− 0.19 [− 0.48 to 0.13] mmol/L vs. 1.17 [3.31–0.77] mmol/L, P = 0.034). In conclusion, forced-air prewarming decreases the incidence and duration of intraoperative hypothermia with potential clinical benefit while mainly acting by preventing the core-to-peripheral heat redistribution. Clinical trial registration: Registered at the Clinical Research Information Service (https://cris.nih.go.kr, [KCT0003230]) on 01/10/2018. [ABSTRACT FROM AUTHOR]

Background: Intermittent hepatic inflow occlusion (IHIO) is associated with acute hyperglycemia during living donor hepatectomy when the ischemia is prolonged. Bilirubin is a potent antioxidant to play an important role for maintaining insulin sensitivity and preventing hyperglycemia. Thus, we aimed to test whether serum bilirubin level is associated with prolonged IHIO-induced intraoperative hyperglycemia. Methods: Seventy-five living liver donors who underwent a prolonged IHIO with a >30 minute cumulative ischemia were included. The association between preoperative serum bilirubin concentrations and the risk of intraoperative hyperglycemia (blood glucose concentration >180 mg/dl) was analyzed using binary logistic regression with adjusting for potential confounders including age and steatosis. Results: The number of donors who underwent 3, 4, 5, and 6 rounds of IHIO was 41, 22, 7, and 5, respectively. Twenty-nine (35%) donors developed intraoperative hyperglycemia. Total bilirubin concentration was inversely associated with hyperglycemia risk (odds ratio [OR] 0.033, 95% confidence interval [CI] 0.004–0.313, P = 0.003). There was an interaction between age and total bilirubin concentration: the effect of lower serum total bilirubin (≤0.7 mg/dl) on the development of hyperglycemia was greater in older donors (>40 years) than in younger donors (P = 0.0.028 versus P = 0.212). Both conjugated bilirubin (OR 0.001 95% CI 0.001–0.684) and unconjugated bilirubin (OR 0.011 95% CI 0.001–0.246) showed an independent association with hyperglycemia risk. Conclusions: Lower preoperative serum bilirubin was associated with greater risk of prolonged IHIO-induced hyperglycemia during living donor hepatectomy particularly in older donors. Thus, more meticulous glycemic management is recommended when prolonged IHIO is necessary for surgical purposes in old living donors with lower serum bilirubin levels. [ABSTRACT FROM AUTHOR]

Background: Children receiving proton therapy require repeated sedation. In this study, we aimed to investigate the utility of the perfusion index (PI) for evaluating consciousness level during repeated propofol sedation. Methods: In this prospective observational study, children aged from birth to 19 years old scheduled for proton therapy under repeated propofol sedation were enrolled. The primary outcome was the equivalence of PI values 5 min after anesthesia induction on consecutive sedation. Total consumption of propofol during sedation, time to reach the University of Michigan sedation scale (UMSS) score 1 after end of proton therapy, and duration of post‐anesthesia care unit (PACU) stay were recorded. Results: The PI values measured 5 min after induction of anesthesia were not equivalent to each other in consecutive sedation except for the second versus third (1st vs. 2nd: 97.5% CI: −1.34, 0.91; p = 0.206, 0.034; 2nd vs. 3rd: 97.5% CI: −0.87, 0.94; p = 0.023, 0.036 3rd vs. 4th: 97.5% CI: −2.08, −0.26; p < 0.99, <0.001; 4th vs. 5th: 97.5% CI: 0.21, 2.28; p < 0.001, >0.99; respectively). In consecutive sedation, there was not a significantly different difference in the time to reach UMSS score 1 (p > 0.99, all) for total consumption of propofol, time to reach UMSS score 1 after the end of proton therapy, and duration of PACU stay. Conclusions: During repeated propofol sedation in children, PI was insufficient to be used as an indicator of consciousness level assessment. However, we suggest that the information related to repeated sedation provided by this study may be helpful in clinical practice. [ABSTRACT FROM AUTHOR]

The radial artery is commonly used as the site measuring pulse pressure variation (PPV) during surgery. Accurate measurement of circulating blood volume and timely interventions to maintain optimal circulating blood volume is important to deliver sufficient oxygen to tissues and organs. It has not rather than never studied in patients undergoing liver transplantation whether PPV measured at peripheral sites, such as the radial artery, do represent central PPV for evaluating blood volume. In this retrospective study, 51 liver transplant recipients were enrolled. The two PPVs had been automatically recorded every minute in electrical medical records. A total 1878 pairs of the two PPVs were collected. The interchangeability of PPV measured at the radial and the femoral artery was analyzed by using the Bland–Altman plot, four-quadrant plot, Cohen's kappa (k), and receiver operating curve. The bias and limits of agreement of the two PPVs were −1.3% and −8.8% to 6.2%, respectively. The percentage error was 75%. The concordance rate was 65%. The Kappa of PPV-radial determining whether PPV-femoral was >13% or ≤13% was 0.64. We found that PPV-radial is not interchangeable with PPV-femoral during liver transplantation. Additionally, PPV-radial failed to reliably track changes of PPV-femoral. Lastly, the clinical decision regarding blood volume status (depletion or not) is significantly different between the two PPVs. Therefore, PPV-femoral may help maintain blood volume circulating to major organs including the newly transplanted liver graft for liver transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows, and eyelashes, for which treatments are limited. Baricitinib, an oral, selective, reversible inhibitor of Janus kinases 1 and 2, may interrupt cytokine signaling implicated in the pathogenesis of alopecia areata.Methods: We conducted two randomized, placebo-controlled, phase 3 trials (BRAVE-AA1 and BRAVE-AA2) involving adults with severe alopecia areata with a Severity of Alopecia Tool (SALT) score of 50 or higher (range, 0 [no scalp hair loss] to 100 [complete scalp hair loss]). Patients were randomly assigned in a 3:2:2 ratio to receive once-daily baricitinib at a dose of 4 mg, baricitinib at a dose of 2 mg, or placebo. The primary outcome was a SALT score of 20 or less at week 36.Results: We enrolled 654 patients in the BRAVE-AA1 trial and 546 in the BRAVE-AA2 trial. The estimated percentage of patients with a SALT score of 20 or less at week 36 was 38.8% with 4-mg baricitinib, 22.8% with 2-mg baricitinib, and 6.2% with placebo in BRAVE-AA1 and 35.9%, 19.4%, and 3.3%, respectively, in BRAVE-AA2. In BRAVE-AA1, the difference between 4-mg baricitinib and placebo was 32.6 percentage points (95% confidence interval [CI], 25.6 to 39.5), and the difference between 2-mg baricitinib and placebo was 16.6 percentage points (95% CI, 9.5 to 23.8) (P<0.001 for each dose vs. placebo). In BRAVE-AA2, the corresponding values were 32.6 percentage points (95% CI, 25.6 to 39.6) and 16.1 percentage points (95% CI, 9.1 to 23.2) (P<0.001 for each dose vs. placebo). Secondary outcomes for baricitinib at a dose of 4 mg but not at a dose of 2 mg generally favored baricitinib over placebo. Acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more common with baricitinib than with placebo.Conclusions: In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. Longer trials are required to assess the efficacy and safety of baricitinib for alopecia areata. (Funded by Eli Lilly under license from Incyte; BRAVE-AA1 and BRAVE-AA2 ClinicalTrials.gov numbers, NCT03570749 and NCT03899259.). [ABSTRACT FROM AUTHOR]

We present a rare case of successful anesthetic management for a patient who had refractory hypoxia during liver transplantation (LT) with intraoperative veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support. A 49 year-old female patient underwent living donor LT. After reperfusion of the grafted liver, graft congestion and massive oozing developed. Thus it was decided to reoperate with a temporary gauze packing. However, the patient's condition deteriorated with azotemia and severe hypoxemia. VV ECMO with continuous renal replacement therapy was started 24 hours before secondary LT and maintained during secondary LT. VV ECMO was weaned 32 hours after secondary LT. This case indicates that not only after the LT but also before and during LT, VV ECMO can be a treatment option for the patient with end-stage liver disease combined with respiratory failure when there is the possibility of lung recovery. [ABSTRACT FROM AUTHOR]

Porphyrias are a group of diseases characterized by an enzyme deficiency in the heme biosynthesis pathway, resulting in accumulation of precursor molecules in the tissue. Some porphyric patients develop progressive liver disease that requires liver transplantation. This case report describes special anesthetic challenges, including careful selection of drugs and the use of special filters that can exclude harmful wavelengths of ultraviolet, in a patient with porphyria who underwent living donor liver transplantation. Understanding the patient's status and disease process, and avoiding triggering factors of porphyria attacks, are important for successful liver transplantation anesthesia in patients with porphyria. [ABSTRACT FROM AUTHOR]

Purpose: We investigated whether hypokalemia developed during the postoperative period and whether the use of intravenous patient-controlled analgesia (IV-PCA) could decrease the incidence of postoperative hypokalemia in patients who underwent laparoscopic cholecystectomy. Methods: Sixty patients undergoing laparoscopic cholecystectomy were randomly assigned to either IV-PCA ( n = 30) or control ( n = 30) groups. We measured serum potassium concentration at the outpatient department (T1), at 8:00 a.m. on the day of surgery (T2), at 6 h after the end of surgery (T3), and at 8:00 a.m. on the first (T4), second (T5), and third (T6) postoperative days. Serum potassium concentration, incidence of hypokalemia, mean blood pressure, heart rate, respiratory rate, and the patient-reported visual analogue scale score were compared within each group and between groups at each time point. Results: Serum potassium concentrations in all patients showed a significant decrease at T2-T4 compared to the preoperative concentration (T1). Serum potassium concentrations at T3 and T4 in the IV-PCA group were significantly higher than those in the control group. Also, the incidence of hypokalemia at T3 and T4 was significantly lower in the IV-PCA group. Mean blood pressure and heart rate were significantly lower in the IV-PCA group than in controls at T3 and T4. Conclusions: The results show that hypokalemia developed during the perioperative period and the use of IV-PCA in patients undergoing laparoscopic cholecystectomy effectively decreased the degree and incidence of postoperative hypokalemia on the day of the operation and postoperative day one. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. As a clinically heterogeneous disease, various classification systems have evolved for defining its severity. In this high-level review of the literature, we discuss the traditional classification systems for AA severity and their strengths and weaknesses. Most recent classifications have focused on the extent of scalp hair loss as a defining feature, but additional clinical aspects of the disease, including location, pattern, and duration of hair loss as well as impact on the patient's quality of life, are also relevant. These various components have typically been used unidimensionally to classify patients. We propose a multidimensional framework to define AA severity that incorporates multiple patient- and illness-related domains. Using such a framework, dermatologists may better assess the severity of the disease for the individual patient beyond the extent of hair loss. [ABSTRACT FROM AUTHOR]

The development of artificial intelligence (AI) and other machine diagnostic systems, also known as software as a medical device , and its recent introduction into clinical practice requires a deeply rooted foundation in bioethics for consideration by regulatory agencies and other stakeholders around the globe. To initiate a dialogue on the issues to consider when developing a bioethically sound foundation for AI in medicine, based on images of eye structures, for discussion with all stakeholders. The scope of the issues and summaries of the discussions under consideration by the Foundational Principles of Ophthalmic Imaging and Algorithmic Interpretation Working Group, as first presented during the Collaborative Community on Ophthalmic Imaging inaugural meeting on September 7, 2020, and afterward in the working group. Artificial intelligence has the potential to improve health care access and patient outcome fundamentally while decreasing disparities, lowering cost, and enhancing the care team. Nevertheless, substantial concerns exist. Bioethicists, AI algorithm experts, as well as the Food and Drug Administration and other regulatory agencies, industry, patient advocacy groups, clinicians and their professional societies, other provider groups, and payors (i.e., stakeholders) working together in collaborative communities to resolve the fundamental ethical issues of nonmaleficence, autonomy, and equity are essential to attain this potential. Resolution impacts all levels of the design, validation, and implementation of AI in medicine. Design, validation, and implementation of AI warrant meticulous attention. The development of a bioethically sound foundation may be possible if it is based in the fundamental ethical principles of nonmaleficence, autonomy, and equity for considerations for the design, validation, and implementation for AI systems. Achieving such a foundation will be helpful for continuing successful introduction into medicine before consideration by regulatory agencies. Important improvements in accessibility and quality of health care, decrease in health disparities, and lower cost thereby can be achieved. These considerations should be discussed with all stakeholders and expanded on as a useful initiation of this dialogue. [ABSTRACT FROM AUTHOR]

Medical innovation is crucial to advancing our field, and physicians have the potential to play a leading role due to their daily patient care experiences. The objective of this study was to evaluate the interest in, and barriers to participating in innovation. Two surveys were conducted; the first cross-sectional survey was conducted among attendees of the Advancing Innovation in Dermatology Forum in Feburary 2019. The second survey was conducted among trainees (resident/fellows) and faculty dermatologists at Brown, Emory, Iowa, Stanford, and Vanderbilt Universities between June and November 2019. Demographic data were collected, as well as factors involved with identifying problems, developing solutions, training in innovation, and perceived barriers to innovation. In the first survey, the greatest perceived benefits include bringing joy to one's work and increasing professional fulfillment with work. Innovation was also perceived to decrease burnout. In the second survey of academic centers, faculty more commonly expressed interest in identifying problems (p = 0.04), and was also more confident in their ability to generate solutions to these problems as compared to trainees (p < 0.01). Major barriers to participating in innovation processes included lack of time and lack of training or education in innovation. Both trainees and faculty groups noted a lack of knowledge in creating prototypes, understanding regulatory approval for medical products, and inexperience with pitching to investors or obtaining funding. These cross-sectional needs assessment surveys found a strong interest in innovation coupled with a lack of education in innovation processes. These findings suggest an urgent need and opportunity for providing formal training to empower dermatologists with the tools to lead innovation within our field. [ABSTRACT FROM AUTHOR]

Background: Ultrasound is not widely used to evaluate optimal supraglottic airway positioning even though it could potentially be used to identify and correct problem areas. Aims: We evaluated a new ultrasound scoring method to identify the position of the supraglottic airway and detect the location of air leaks during ventilation in pediatric patients. Methods: Using a prospective observational study design, we enrolled 90 pediatric patients of ASA physical status I–III scheduled for elective surgery under general anesthesia. After anesthesia induction, patients were assigned to a noncorrection group or a correction group after their first ultrasound evaluation. Noncorrection group comprised patients with tolerable I‐Gel positioning based on ultrasound evaluation and no problems with clinical parameters, while the correction group comprised patients with I‐Gel mispositioning based on ultrasound. Results: After the first ultrasound evaluation, 61 patients did not need I‐Gel correction (noncorrection group), while 29 patients needed I‐Gel correction (correction group) and underwent a second ultrasound evaluation. Airway sealing pressure and total ultrasound score showed a negative correlation (r = −.845, p <.001). The area under the receiver operating curve for total ultrasound score was 0.97 (95% confidence interval, 0.94–0.99; p <.001). In the correction group, ultrasound score and ventilation parameters improved after correction based on ultrasound evaluation. Conclusions: Ultrasound scores were negatively correlated with airway sealing pressure in pediatric patients. Ultrasound evaluation is useful for detecting misplacement of the I‐Gel and can be a useful tool for correction. [ABSTRACT FROM AUTHOR]