Erosive rheumatoid arthritis in a young patient with mirror hand

Mirror hand is a congenital anomaly characterised by duplication of the ulnar ray, resulting in polydactyly and functional disability of the hand. It can cause arthralgias and weakness in intrinsic muscles of the hand. We present a young woman who had a surgically corrected mirror hand and subsequently developed aggressive rheumatoid arthritis, which increased her limitations to a significant degree. Early diagnosis and treatment in such cases is very important to prevent long-term disability.

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Multiorgan embolisation of a left ventricular thrombus

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'Carpal tunnel syndrome and 'tennis elbow as prodromes for granulomatosis with polyangiitis (formerly Wegeners granulomatosis)

A 62-year-old man presented with excruciating joint pains, back stiffness and numbness of his hands and feet. Over the past 18 months, he had experienced similar episodes for which the diagnoses of bilateral carpal tunnel syndrome and lateral epicondylitis had been made. Physical examination revealed polyarticular arthritis affecting the shoulders, wrists and right knee. Palpable purpura overlying the calves and ankles was present. Laboratory tests showed markedly elevated erythrocyte sedimentation rate and C-reactive protein in the setting of negative blood and urine cultures. Rheumatoid factor and antinuclear antibodies were negative. Chest CT demonstrated bilateral pulmonary infiltrates. A punch biopsy of the rash showed leukocytoclastic vasculitis. Anti-proteinase-3 titers returned strongly positive. A diagnosis of granulomatosis with polyangiitis was made. Treatment with high-dose steroids, followed by rituximab resulted in normalisation of inflammatory markers with subsequent resolution of joint pains, rash and pulmonary infiltrates and improvement of neuropathic symptoms.

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Just one more rash?

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Hydroxychloroquine-induced inverse psoriasis

A 65-year-old woman presented to our rheumatology clinic with pain and swelling of multiple joints of her hands. After a thorough evaluation, she was diagnosed with rheumatoid arthritis and was started on hydroxychloroquine therapy. A week later, she presented to our clinic with an acute condition and reported that after taking hydroxychloroquine for a few days she developed multiple rashes, most prominent at skin folds around her breasts, neck, axillae and buttocks. The rashes were characteristic of inverse psoriasis. Hydroxychloroquine was discontinued and the patient was started on methotrexate therapy that resulted in resolution of her rashes in a week.

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Littres hernia

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Delayed diagnosis of postcardiac injury syndrome

Postcardiac injury syndrome (PCIS) is a rare condition that is considered to have a trauma-induced autoimmune mechanism triggered by damage to pericardial and/or pleural tissues. We report a case of PCIS accompanied by systemic oedema after thymectomy. A 73-year-old woman was referred to our hospital for dyspnoea and oedema, 9 months after thymectomy. Evaluation revealed the presence of pericardial effusion, pleural effusion and systemic oedema. Differential diagnosis included constrictive pericarditis (secondary to tuberculosis), serositis caused by collagen disease and malignancy. Detailed investigations led to the diagnosis of PCIS, which was successfully treated with prednisolone. This report focuses on the diagnostic approach to PCIS. Since it took time to make a final diagnosis in our patient, we analysed several past case reports and series to determine the cause of the delay in diagnosis.

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Mandibular resorption and vocal cord paralysis: a catastrophic form of systemic sclerosis

Sudden respiratory distress in association with severe weight loss are unusual features of systemic sclerosis (SSc). We report the case of a 56-year-old Caucasian woman with a 9-year history of a diffuse form of SSc who presented with acute stridor due to vocal cord paralysis and required an emergency tracheostomy. She had sought medical attention only after 4 years of disease onset, presenting with a mask-like face, diffuse skin thickening, acro-osteolysis and severe interstitial lung disease. Even though skin tightness improved after immunosuppressive treatment, several spontaneous facial fractures and episodes of dysphagia and choking occurred in the years that followed. At the time of stridor, she was severely malnourished and a percutaneous endoscopic gastrostomy was required for feeding. Permanent vocal cord damage in combination with severe loco-regional bone resorption resulted in severe disability and impaired nutrition. We hereby highlight the features of SSc for which therapy remains challenging.

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Neuroleptic malignant syndrome as part of an akinetic crisis associated with sepsis in a patient with Lewy body disease

A 65-year-old Japanese woman with Parkinson's disease, later diagnosed with Lewy body disease, presented with a 2-day history of systemic tremors. She also had fever without rigidity or creatine kinase (CK) elevation. She was diagnosed with sepsis caused by pyelonephritis with acute kidney injury and parkinsonism exacerbation. Although antibiotic and fluid therapy improved her pyuria and renal function, her fever and tremors persisted. On the fourth day, her symptoms worsened and resulted in cardiopulmonary arrest; however, quick resuscitation allowed the return of spontaneous circulation. Simultaneously, hyperthermia, altered consciousness, extrapyramidal symptoms, dysautonomia and CK elevation were noted. Thus, dantrolene administration was initiated with a tentative diagnosis of neuroleptic malignant syndrome (NMS). This caused her fever to subside, and her symptoms gradually improved. It was difficult to distinguish between parkinsonism exacerbation associated with sepsis and NMS. Physicians should consider NMS early on, even if the patient does not fulfil the diagnostic criteria.

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Uncontrolled diabetes as a rare presenting cause of pituitary apoplexy

Pituitary apoplexy is a rare endocrine emergency. The extent to which hyperglycaemia is a contributory risk factor in the precipitation of pituitary apoplexy is not known. A 38-year-old man with poorly controlled diabetes presented to the emergency department with sudden onset of nausea and headache with drooping of his right eyelid for about 4 days. On physical examination, he had orthostatic hypotension, ptosis of the right eye, lateral and downward positioning of the eye and absent pupillary reflex. Visual field testing of the left eye revealed superolateral quadrantanopia. MRI of the brain showed pituitary macroadenoma with necrosis. Investigations showed hyperglycaemia, decreased T3, T4 with normal Thyroid stimulating hormone (TSH), low serum Leutinizing hormone (LH), Follicle stimulating hormone (FSH), testosterone and low normal serum prolactin levels. About 21% of non-functioning pituitary adenomas present with apoplexy as was seen in our patient. It is likely that his uncontrolled diabetes precipitated this episode of apoplexy as hyperosmolarity and dehydration, caused by hyperglycaemia can lead to changed pituitary microvascular environment increasing the risk of pituitary infarction.

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Xanthoma and paraproteinaemia: a spot diagnosis

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Severe asthma ‐ A population study perspective

Abstract

Background

Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.

Objective

To describe characteristics and estimate the prevalence of severe asthma in a large adult population‐based asthma cohort followed for 10‐28 years.

Methods

N=1006 subjects with asthma participated in a follow‐up during 2012‐14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well‐known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.

Results

The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.

Conclusions and clinical relevance

Severe asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4‐6%, corresponding to approximately 0.5% of the general population.

This article is protected by copyright. All rights reserved.

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Efficacy and safety of Brentuximab Vedotin in advanced cutaneous T‐Cell lymphomas patients

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Did Mona Lisa suffer from postpartum thyroiditis?

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A juvenile male case of dermatofibrosarcoma protuberans on the breast

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Accidental re‐exposure causing repeated severe acute generalized exanthematous pustulosis

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Reply to: “Could Isotretinoin flare Hidradentis suppurativa? A Case Series”

Abstract

We read with interest the manuscript recently published by Gallagher¹et al. concerning eight patients with severe acne who were treated with isotretinoin and developed hidradenitis suppurativa (HS). Conversely to the authors, we experienced flares in patients with HS treated with retinoids. We report three cases of patients with moderate‐severe HS localized in their axillae and groins.

This article is protected by copyright. All rights reserved.

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[18F]‐Fluorodeoxy‐D‐glucose uptake in prurigo nodules induced by the membranous expression of glucose transporter

Abstract

Positron emission tomography‐computed tomography (PET/CT) is a valuable imaging modality for assessing malignant tumours; however, the aberrant uptake of [¹⁸F]‐fluorodeoxy‐D‐glucose (FDG) is sometimes observed in benign skin lesions such as corns, seborrhoeic keratosis, viral warts, condyloma acuminatum, rhinophymas, and acne vulgaris^1,2. We encountered a case of prurigo nodularis associated with abnormal uptake of FDG and evaluated the expression of the glucose transporter in the lesions. A 55‐year‐old male with a pulmonary metastasis of malignant melanoma received nivolumab. After three years' nivolumab administration, a PET/CT was performed to evaluate the effect of the immunotherapy.

This article is protected by copyright. All rights reserved.

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Ustekinumab for skin reactions associated with anti‐tumor necrosis factor‐α agents in patients with inflammatory bowel diseases: A single‐center retrospective study

Abstract

Anti‐tumor necrosis factor (TNF)‐α agents may induce skin reactions, in particular in patients with inflammatory bowel diseases (IBD). The objective of this study was to determine the efficacy of ustekinumab in these patients. IBD patients facing therapeutic issues because of cutaneous reactions or tolerance issues, consequently treated with ustekinumab in our department, were included. Retrospective review of case records and clinical photographs was carried out. Twenty‐six patients were included. Twenty‐three patients were treated for Crohn's disease and three for ulcerative colitis. Fourteen patients presented psoriasiform lesions, nine eczematiform lesions, four anaphylactoid reactions, two alopecia areata‐like lesions, one injection‐site reaction, one cutaneous polyarteritis nodosa and five other skin reactions. Most of them resolved under ustekinumab. In detail, eczematiform lesions completely resolved in all cases, psoriasiform lesions completely resolved in 12 cases (85.7%) and had partial response in two cases (14.3%). Two cases of alopecia areata showed complete response (complete hair regrowth). Fourteen patients showed complete digestive response, 10 patients partial digestive response (seven of which needed IBD treatment optimization) and only two failure. In conclusion, ustekinumab is a drug of choice in patients with IBD who cannot tolerate TNF blockers.

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Fiberglass dermatitis: clinical presentations, prevention, and treatment – a review of literatures

Abstract

Fiberglass dermatitis is a common form of occupational irritant contact dermatitis. Individuals experience a negative reaction to fiberglass fragments because of mechanical irritation. This review comprehensively analyzes the information in the existing literature on fiberglass dermatitis. Recognizing the different environmental risks factors for acquiring fiberglass dermatitis is necessary for better diagnosis and prevention. In addition to the identification of high‐risk populations exposed to fiberglass particles, the common clinical presentation and preventive measures that can reduce the risk of acquiring fiberglass dermatitis are thoroughly discussed.

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Extending the phenotypic spectrum associated with mosaicism for GJB2 mutations

Abstract

Cutaneous mosaicism is a common phenomenon resulting from postzygotic mutations. Mosaic skin lesions are manifold, and they may be accompanied by abnormalities of other organs. Here we investigated a young man with complex clinical features as part of a mosaic phenotype.

This article is protected by copyright. All rights reserved.

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miR‐145‐5p regulates fibrotic features of recessive dystrophic epidermolysis bullosa skin fibroblasts

Summary

Background

Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disorder caused by mutations in the COL7A1 gene encoding type VII collagen, a cutaneous basement membrane component essential for epidermal‐dermal adhesion. Hallmarks of the disease are unremitting blistering and chronic wounds with severe inflammation and fibrosis. microRNAs are post‐transcriptional regulators of gene expression also implicated in fibrotic processes. However, the role of microRNAs in RDEB fibrosis is almost unexplored.

Objectives

Our study aimed at identifying microRNAs deregulated in primary RDEB skin fibroblasts (RDEBFs) and at characterizing their function in RDEB fibrosis.

Methods

qRT‐PCR was used to screen RDEBFs for the expression levels of a group of microRNAs deregulated in hypertrophic scars and keloids, pathological conditions with abnormal wound healing and fibrosis. Contractility, proliferation and migration rate were evaluated by different in vitro assays in RDEBFs transfected with a miR‐145‐5p inhibitor. qRT‐PCR and western blot analysis provided the expression levels of fibrotic markers and miR‐145‐5p targets.

Results

The miR‐143/145 cluster was up‐regulated in RDEBFs with respect to fibroblasts from healthy subjects. RDEBFs transfected with a miR‐145‐5p inhibitor showed attenuated fibrotic traits, i.e. contraction, proliferation and migration, accompanied by reduced expression of the contractile proteins α‐smooth muscle actin and transgelin. These effects were associated with the up‐regulation of kruppel like factor 4 transcriptional repressor and the down‐regulation of Jagged 1, a known inducer of fibrosis.

Conclusions

Our results highlight the pro‐fibrotic role of miR‐145‐5p and its regulatory networks in RDEB, shedding light on novel disease pathomechanisms and targets for future therapeutic approaches.

This article is protected by copyright. All rights reserved.

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Anesthetic Implications of the New Guidelines for Button Battery Ingestion in Children

Button battery ingestions result in significant morbidity and mortality in children—before, during, and even after removal. The injuries created by a button battery lodged in the esophagus develop rapidly and can be severe. The current of the button battery, conducted through saliva and the tissue drives a highly alkaline caustic injury, leading to liquefactive tissue necrosis. In June 2018, new guidelines were released from the National Capital Poison Center, which include the use of preoperative protective, pH-neutralizing and viscous barrier interventions with honey and/or sucralfate administered within 12 h of ingestion. In addition, the use of postremoval irrigation of the esophagus with 50–150 mL 0.25% acetic acid is done in the operating room to help neutralize the site of tissue injury. Given that anesthesiologists play an important role in the management of esophageal foreign body removal, the entire specialty needs to be aware of the supporting data behind this and general perioperative considerations for management and potential complications of button battery ingestion. Accepted for publication December 13, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Debnath Chatterjee, MD, FAAP, Department of Anesthesiology, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 E 16th Ave, B090, Aurora, CO 80045. Address e-mail to debnath.chatterjee@childrenscolorado.org. © 2019 International Anesthesia Research Society

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Culture-Negative and Culture-Positive Sepsis: A Comparison of Characteristics and Outcomes

BACKGROUND: The primary objective of this study was to compare the characteristics of culture-positive and culture-negative status in septic patients. We also determined whether culture status is associated with mortality and whether unique variables are associated with mortality in culture-positive and culture-negative patients separately. METHODS: Utilizing patient records from intensive care units, emergency department, and general care wards in a large academic medical center, we identified adult patients with suspected infection and ≥2 systemic inflammatory response syndrome criteria between January 1, 2007, and May 31, 2014. We compared the characteristics between culture-positive and culture-negative patients and used binary logistic regression to identify variables independently associated with culture status and mortality. We also did sensitivity analyses using patients with Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria for sepsis. RESULTS: The study population included 9288 culture-negative patients (89%) and 1105 culture-positive patients (11%). Culture-negative patients received more antibiotics during the 48 hours preceding diagnosis but otherwise demonstrated similar characteristics as culture-positive patients. After adjusting for illness severity, a positive culture was not independently associated with mortality (odds ratio = 1.01 [95% CI, 0.81–1.26]; P = .945). The models predicting mortality separately in culture-negative and culture-positive patients demonstrated very good and excellent discrimination (C-statistic ± SD, 0.87 ± 0.01 and 0.92 ± 0.01), respectively. In the sensitivity analyses using patients with sepsis by Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria, after adjustments for illness severity, positive cultures were still not associated with mortality (odds ratio = 1.13 [95% CI, 0.86–1.43]; P = .303; and odds ratio = 1.05 [95% CI, 0.83–1.33]; P = .665), respectively. In all models, physiological derangements were associated with mortality. CONCLUSIONS: While culture status is important for tailoring antibiotics, culture-negative and culture-positive patients with sepsis demonstrate similar characteristics and, after adjusting for severity of illness, similar mortality. The most important factor associated with negative cultures is receipt of antibiotics during the preceding 48 hours. The risk of death in patients suspected of having an infection is most associated with severity of illness. This is aligned with the Sepsis-3 definition using Sequential Organ Failure Assessment score to better identify those suspected of infection at highest risk of a poor outcome. Accepted for publication January 8, 2019. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Matthew J. G. Sigakis, MD, Division of Critical Care Medicine, Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109. Address e-mail to msigakis@med.umich.edu. © 2019 International Anesthesia Research Society

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Early Treatment With Metformin in a Mice Model of Complex Regional Pain Syndrome Reduces Pain and Edema

BACKGROUND: Metformin, an adenosine monophosphate (AMP)–activated protein kinase activator, as well as a common drug for type 2 diabetes, has previously been shown to decrease mechanical allodynia in mice with neuropathic pain. The objective of this study is to determine if treatment with metformin during the first 3 weeks after fracture would produce a long-term decrease in mechanical allodynia and improve a complex behavioral task (burrowing) in a mouse tibia fracture model with signs of complex regional pain syndrome. METHODS: Mice were allocated into distal tibia fracture or nonfracture groups (n = 12 per group). The fracture was stabilized with intramedullary pinning and external casting for 21 days. Animals were then randomized into 4 groups (n = 6 per group): (1) fracture, metformin treated, (2) fracture, saline treated, (3) nonfracture, metformin treated, and (4) nonfracture, saline treated. Mice received daily intraperitoneal injections of metformin 200 mg/kg or saline between days 14 and 21. After cast removal, von Frey force withdrawal (every 3 days) and burrowing (every 7 days) were tested between 25 and 56 days. Paw width was measured for 14 days after cast removal. AMP-activated protein kinase downregulation at 4 weeks after tibia fracture in the dorsal root ganglia was examined by immunohistochemistry for changes in the AMP-activated protein kinase pathway. RESULTS: Metformin injections elevated von Frey thresholds (reduced mechanical allodynia) in complex regional pain syndrome mice versus saline-treated fracture mice between days 25 and 56 (difference of mean area under the curve, 42.5 g·d; 95% CI of the difference, 21.0–63.9; P

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Real-Time Ultrasound Improves Accuracy of Caudal Block in Children

BACKGROUND: Caudal block, the most common regional anesthetic in children, is predominantly performed using palpation to determine placement. The efficacy of the palpation technique is unknown with respect to block success. While ultrasound has been suggested for use during caudal block, its use is infrequent. METHODS: A single-blinded prospective observational trial was performed evaluating provider success rate of caudal blocks placed by palpation alone. After needle insertion and partial local anesthetic injection, an ultrasound was performed to confirm correct location. RESULTS: A total of 109 caudal blocks were performed during the prospective observational study. Success rate for caudal blocks done by palpation alone was 78.9% as confirmed by ultrasound. In 21.1% of caudal blocks, the provider incorrectly judged the needle to be in the caudal space as confirmed with ultrasound. CONCLUSIONS: Real-time ultrasound visualization of local anesthetic injection provides reliable and immediate confirmation during caudal block in children. Accepted for publication January 8, 2019. Funding: Departmental. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). This work was presented in abstract form at the 43rd Annual Regional Anesthesiology and Acute Pain Medicine Meeting, New York, NY, April 21, 2018. Reprints will not be available from the authors. Address correspondence to Adam C. Adler, MD, MS, FAAP, FASE, Texas Children's Hospital, Baylor College of Medicine, 6621 Fannin St, Suite #A3300, Houston, TX 77030. Address e-mail to adam.adler@bcm.edu. © 2019 International Anesthesia Research Society

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Hypertonic Saline in Human Sepsis: A Systematic Review of Randomized Controlled Trials

The role of hypertonic saline in sepsis remains unclear because clinical data are limited and the balance between beneficial and adverse effects is not well defined. In this systematic literature review, we searched PubMed and Embase to identify all randomized controlled trials up until January 31, 2018 in which hypertonic saline solutions of any concentration were used in patients of all ages with sepsis and compared to a cohort of patients receiving an isotonic fluid. We identified 8 randomized controlled trials with 381 patients who had received hypertonic saline. Lower volumes of hypertonic saline than of isotonic solutions were needed to achieve the desired hemodynamic goals (standardized mean difference, −0.702; 95% CI, −1.066 to −0.337; P

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Dose–Response Study of 4 Weight-Based Phenylephrine Infusion Regimens for Preventing Hypotension During Cesarean Delivery Under Combined Spinal–Epidural Anesthesia

BACKGROUND: Prophylactic IV infusion of phenylephrine has been recommended to prevent hypotension during spinal anesthesia for cesarean delivery. However, the optimal infusion dose is unknown. This study aimed to determine the infusion dose of phenylephrine that would be effective in preventing hypotension in 50% (ED50) and 90% (ED90) of patients when administered as a prophylactic infusion at a fixed rate based on the individual body weight. METHODS: Eighty parturients scheduled for elective cesarean delivery were randomly allocated to receive IV infusion of prophylactic phenylephrine at 0.25, 0.375, 0.5, or 0.625 µg/kg/min (n = 20 per group) started immediately after intrathecal injection of 10 mg hyperbaric bupivacaine and 5 µg sufentanil using a combined spinal–epidural technique. An effective dose was defined by the occurrence of no hypotension (defined as a decrease in systolic blood pressure by ≥20% below baseline and to

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Road to Perioperative Medicine: A Perspective From China

With the development of anesthesiology, patient safety has been remarkably improved, but the postoperative mortality rate at 30 days is still as high as 0.56%–4%, and the morbidity is even higher. Three years ago, the Chinese Society of Anesthesiology proposed that the direction of the anesthesiology development should be changed to perioperative medicine in China. Anesthesiologists should pay more attention to the long-term outcome. In this article, we introduced what we have done, what the challenges are, and what we should do in the future with regard to the practice of perioperative medicine in China. Accepted for publication January 8, 2019 Funding: This study was partly supported by the National Natural Science Foundation of China (Grant No. 81842018). The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Lize Xiong, MD, PhD, Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China 710032. Address e-mail to mzkxlz@126.com. © 2019 International Anesthesia Research Society

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Customizable Curriculum to Enhance Resident Communication Skills

Communication remains challenging to teach and evaluate. We designed an online patient survey to assess anesthesia residents' communication skills from August 2014 to July 2015. In December 2014, we implemented a customized, simulation-based curriculum. We calculated an overall rating for each survey by averaging the ratings for the individual questions. Based on the Hodges–Lehmann 2-sample aligned rank-sum test, overall ratings, reported as the median (interquartile range) of residents' average overall ratings, differed significantly between the preintervention (3.86 [3.76–3.94]) and postintervention (3.91 [3.84–3.95]) periods (P = .025). Future studies should assess the intervention's effectiveness and generalizability. Accepted for publication January 16, 2019. Funding: This study was funded by the Department of Anesthesia, Critical Care and Pain Medicine at Beth Israel Deaconess Medical Center, Boston, MA. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to John D. Mitchell, MD, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Rd, RB-470, Boston, MA 02215. Address e-mail to jdmitche@bidmc.harvard.edu. © 2019 International Anesthesia Research Society

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Proliferator-Activated Receptor-Gamma Coactivator-1α Haploinsufficiency Promotes Pain Chronification After Burn Injury

BACKGROUND: Tissue injuries such as surgery and trauma are usually accompanied by simultaneous development of acute pain, which typically resolves along with tissue healing. However, in many cases, acute pain does not resolve despite proper tissue repair; rather, it transitions to chronic pain. In this study, we examined whether proliferator-activated receptor-gamma coactivator-1α (PGC-1α), a master regulator of mitochondria biogenesis, is implicated in pain chronification after burn injury in mice. METHODS: We used PGC-1α+/+ and littermates PGC-1α+/− mice of both sex. Burn injury was induced on these mice. Hindpaw mechanical withdrawal thresholds and thermal withdrawal latency were examined. RESULTS: Hindpaw mechanical withdrawal thresholds and thermal withdrawal latencies were comparable at baseline between PGC-1α+/− and PGC-1α+/+ mice. After burn injury, both PGC-1α+/+ and PGC-1α+/− mice exhibited an initial dramatic decrease of withdrawal parameters at days 3 and 5 after injury. While PGC-1α+/+ mice fully recovered their withdrawal parameters to preinjury levels by days 11–14, PGC-1α+/− mice failed to recover those parameters during the same time frame, regardless of sex. Moreover, we found that PGC-1α+/− mice resolved tissue inflammation in a similar fashion to PGC-1α+/+ mice using a chemiluminescence-based reactive oxygen species imaging technique. CONCLUSIONS: Taken together, our data suggest that PGC-1α haploinsufficiency promotes pain chronification after burn injury. Accepted for publication January 16, 2019. J. Miao and X. Zhou contributed equally and share first authorship. The authors declare no conflicts of interest. Funding: J.M. is supported by R01DE02290 and R01DA039925. S.S. is supported by the Foundation of Anesthesia Education and Research, National Institute of General Medical Sciences R35-GM1286928, and research fund from the Department of Anesthesia, Critical Care and Pain Medicine at the Massachusetts General Hospital. Reprints will not be available from the authors. Address correspondence to Shiqian Shen, MD, Department of Anesthesia, Critical Care and Pain Medicine, Center for Translational Pain Research, Massachusetts General Hospital, Harvard Medical School, Jackson Bldg 458, 55 Fruit St, Boston, MA 02121. Address e-mail to sshen2@mgh.harvard.edu. © 2019 International Anesthesia Research Society

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Retrospective Analysis of Obstetric Intensive Care Unit Admissions Reveals Differences in Etiology for Admission Based on Mode of Conception

BACKGROUND: The use of in vitro fertilization is increasing. The incidence of adverse outcomes is greater for women who undergo in vitro fertilization, potentially leading to intensive care unit admission. This study aimed to assess the etiology and course of intensive care unit admission in women who underwent in vitro fertilization compared to those who did not, with specific focus on intensive care unit admission due to postpartum hemorrhage. METHODS: In this retrospective study, medical records of patients admitted to the intensive care unit during pregnancy or the peripartum period at 2 medical centers (2005–2016 at Mount Sinai Hospital, New York, NY, and 2005–2013 at Shaare Zedek Medical Center, Jerusalem, Israel) were analyzed. Demographic, past medical and obstetric history, and details regarding delivery and intensive care unit stay were collected, as was information regarding mode of conception (in vitro fertilization versus non–in vitro fertilization) for the current pregnancy. The primary outcome measure was difference in etiology of intensive care unit admission between in vitro fertilization and non–in vitro fertilization groups. Secondary outcome measures included differences in prepregnancy characteristics, incidence, severity, and management of postpartum hemorrhage, as well as incidence of other clinical major morbidity events and delivery-related complications. Multivariable logistic regression was performed to study the relationship between in vitro fertilization and the odds of having been admitted to the intensive care unit due to hemorrhage. RESULTS: During the study period, there were nearly 192,000 deliveries, with 428 pregnant and peripartum women admitted to the intensive care unit. Of the 409 cases analyzed, 60 had conceived following in vitro fertilization and 349 had conceived without in vitro fertilization. The non–in vitro fertilization group was more likely to have multiple medical comorbidities, and the in vitro fertilization group was more likely to have multiple gestations. The groups also differed in etiology of intensive care unit admission; more women in the in vitro fertilization group were admitted due to a pregnancy-related complication. Intensive care unit admission for postpartum hemorrhage was more frequent in the in vitro fertilization group (60.0% vs 43.1%, P = .014), with a 2-fold increase in the incidence of hemorrhagic shock. Logistic regression analysis revealed a 2-fold increase in the odds that intensive care unit admission was due to hemorrhage in women undergoing in vitro fertilization, a finding that was not statistically significant when multiple gestation was added to the model. CONCLUSIONS: Among patients admitted to the intensive care unit, patients with different modes of conception had dissimilar etiologies for intensive care unit admission with intensive care unit admission due to hemorrhage greater in those with in vitro fertilization. Higher rates of multiple gestation pregnancies may explain this difference. Differences in pregnancies conceived via in vitro fertilization versus without in vitro fertilization may affect the obstetric intensive care unit case mix. Accepted for publication January 2, 2019. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Diana N. Romano, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl, Box 1010 New York, NY 10029. Address e-mail to diana.romano@mountsinai.org. © 2019 International Anesthesia Research Society

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Core Topics in Preoperative Anaesthetic Assessment and Management

No abstract available

https://ift.tt/2EDTaff

Minocycline Relieves Depressive-Like Behaviors in Rats With Bone Cancer Pain by Inhibiting Microglia Activation in Hippocampus

BACKGROUND: Pain and depression are highly prevalent symptoms in cancer patients. They tend to occur simultaneously and affect each other and share biological pathways and neurotransmitters. In this study, we investigated the roles of microglia in the hippocampus in the comorbidity of bone cancer pain and depressive-like behaviors in an animal model of bone cancer pain. METHODS: Bone cancer pain was induced by injection of Walker 256 mammary gland carcinoma cells into the tibia of rats. The effects of intracerebroventricular administration of microglia inhibitor minocycline were examined. RESULTS: Carcinoma intratibia injection caused comorbidity of mechanical allodynia and depressive-like behaviors in rats and activation of microglia in the hippocampus. Both mechanical allodynia and depressive-like behaviors were attenuated by minocycline. Enzyme-linked immunosorbent assay analysis showed that the enhanced expressions of M1 microglia marker (CD 86) and the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the hippocampus of cancer-bearing rats were decreased by minocycline. On the other hand, minocycline also increased the expressions of M2 microglia marker (MRC1) and anti-inflammatory cytokine interleukin-10. CONCLUSIONS: The results suggest that the activation of microglia in the hippocampus plays an important role in the development of pain and depressive-like behaviors in bone cancer condition. Accepted for publication January 3, 2019. The authors declare no conflicts of interest. Funding: Nature Science Foundation of Hunan Province (2018JJ3836 to S.Z.), National Nature Science Foundation of China (81300958 to S.Z.), and Nature Science Foundation of Hunan Province (S2016J504F2145 to Z.J.). Reprints will not be available from the authors. Address correspondence to Zongbin Song, MD, PhD, Department of Anesthesiology, Xiangya Hospital, Central S. University, Hunan, China. Address e-mail to songzb2001@163.com. © 2019 International Anesthesia Research Society

https://ift.tt/2VtxJCX

Methylprednisolone Does Not Reduce Acute Postoperative Pain After Cardiac Surgery: Subanalysis of a Randomized Clinical Trial

BACKGROUND: Pain after cardiac surgery is largely treated with opioids, but their poor safety profile makes nonopioid medications attractive as part of multimodal pathways. Anti-inflammatory drugs reduce acute postoperative pain, but the role of steroids in reducing acute poststernotomy pain is unclear. We evaluated the association between the intraoperative administration of methylprednisolone and postoperative analgesia, defined as a composite of pain scores and opioid consumption, during the initial 24 hours after cardiac surgery. METHODS: We conducted a post hoc retrospective analysis of a large clinical trial in which adults having cardiac surgery were randomized 1:1 to receive 2 intraoperative doses of 250 mg IV methylprednisolone or placebo. Pain scores and opioid consumption were collected during the initial 24 hours after surgery. Methylprednisolone was considered to be associated with better pain control than placebo if proven noninferior (not worse) on both pain scores (defined a priori with delta of 1 point) and opioid consumption (delta of 20%) and superior to placebo in at least 1 of the 2 outcomes. This test was repeated in the opposite direction (testing whether placebo is better than methylprednisolone on postoperative pain management). RESULTS: Of 251 eligible patients, 127 received methylprednisolone and 124 received placebo. Methylprednisolone was noninferior to placebo on pain with difference in mean (CI) pain scores of −0.25 (−0.71 to 0.21); P

https://ift.tt/2EFTxpH

Gupta and Gelb’s Essentials of Neuroanesthesia and Neurointensive Care

No abstract available

https://ift.tt/2VtOFcM

Suppression of Human Natural Killer Cells by Different Classes of Opioids

BACKGROUND: The use of regional and other opioid-sparing forms of anesthesia has been associated with a decrease in the recurrence of certain malignancies. Direct suppression of human natural killer cells by opioids has been postulated to explain this observation. However, the effect of different classes of opioids on suppression of natural killer cell cytotoxicity has not been systematically characterized. METHODS: After confirming that freshly isolated natural killer cells from peripheral human blood express opioid receptors, cells were incubated with increasing concentrations of clinically used or receptor-specific opioid agonists. We also evaluated the effect of pretreatment with receptor-specific antagonists or naloxone. Treated natural killer cells were then coincubated with a carboxyfluorescein succinimidyl ester–labeled target tumor cell line, K562. Annexin V staining was used to compare the percent of tumor cell apoptosis in the presence of opioid-pretreated and untreated natural killer cells. Treated samples were compared to untreated samples using Kruskal-Wallis tests with a post hoc Dunn correction. RESULTS: Morphine, methadone, buprenorphine, loperamide, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin, and U-50488 significantly decreased natural killer cell cytotoxicity. When natural killer cells were pretreated with naloxone, cyprodime, and nor-binaltorphimine before exposure to morphine, there was no difference in natural killer cytotoxicity, compared to the amount observed by untreated natural killer cells. Fentanyl, O-desmethyltramadol, and [D-Pen2,D-Pen5]enkephalin did not change natural killer cell cytotoxicity compare to untreated natural killer cells. CONCLUSIONS: Incubation of isolated natural killer cells with certain opioids causes a decrease in activity that is not overserved after naloxone pretreatment. Suppression of natural killer cell cytotoxicity was observed with μ- and κ-receptor agonists but not δ-receptor agonists. These data suggest that the effect is mediated by μ- and κ-receptor agonism and that suppression is similar with many clinically used opioids. Accepted for publication January 3, 2018. Funding: D.P.M. received funding from the Blaustein Pain Research Fund Grant and National Institutes of Health (NIH) Grant 5T32GM075774. N.M.H. receives funding from NIH Grant R01 HL124477. No copyrighted material from outside sources was used in preparation of this manuscript. This study has not been previously presented. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Dermot P. Maher, MD, MS, Johns Hopkins Blaustein Pain Treatment Center, Johns Hopkins University School of Medicine, 601 N Caroline St, Baltimore, MD 21205. Address e-mail to dmaher3@jhmi.edu. © 2019 International Anesthesia Research Society

https://ift.tt/2VsX1kC

Ultrasound-Guided Erector Spinae Plane Block in Patients Undergoing Open Epigastric Hernia Repair: A Prospective Randomized Controlled Study

BACKGROUND: Hernia repair is associated with considerable postoperative pain. We studied the analgesic efficacy of bilateral ultrasound-guided erector spinae plane block in patients undergoing open midline epigastric hernia repair (T6–T9). METHODS: Sixty patients 18–65 years of age were randomly allocated into 2 groups. Patients in the erector spinae plane block group received bilateral ultrasound-guided erector spinae plane block at the level of T7 transverse process using 20 mL of bupivacaine 0.25% on each side, while the control group received bilateral sham erector spinae plane block using 1 mL of normal saline. All patients underwent general anesthesia for surgery. Pain severity (visual analog scale), consumption of intraoperative fentanyl, time to first request of rescue analgesia, and postoperative pethidine consumption were recorded over the first 24 hours postoperatively. RESULTS: At 2 hours postoperatively, the visual analog scale pain score was significantly lower in the erector spinae plane block group compared to the control group (estimated main effect of 2.53; P

https://ift.tt/2EDkc6u

In Response

No abstract available

https://ift.tt/2VpkByN

Association of Preoperative Frailty With Intraoperative Hemodynamic Instability and Postoperative Mortality

BACKGROUND: Frailty, a state of decreased physiological reserve, is strongly associated with perioperative mortality in older adults. However, the mechanism by which frailty is associated with mortality is not yet understood. Autonomic dysfunction in the form of decreased intraoperative hemodynamic variability has been shown to be associated with increased mortality. We aimed to see whether frail patients have less hemodynamic variability under anesthesia and whether variability mediates the relationship between frailty and 30-day mortality. METHODS: We performed a single-center retrospective study of 1223 patients ≥65 years of age undergoing surgery between July 2008 and December 2012. We used markers of frailty: age >70, preoperative body mass index 2.0 mg/dL. We modeled the outcome of 30-day mortality with number of frailty conditions adjusting for gender, length of surgery, American Society of Anesthesiologists class, and need for transfusion. Intraoperative hemodynamic variability was defined as the count of episodes of absolute change >15% in fractional mean arterial pressure (MAP) between consecutive 5-minute intervals. We evaluated the role of intraoperative hemodynamic variability as a mediator (modifier) of the relationship between frailty and mortality, checking for 3 conditions: (1) frailty must affect episodes of absolute change >15% in fractional MAP; (2) episodes of absolute change >15% in fractional MAP must affect 30-day mortality; and (3) mediation effect is significant. We used the product method, in which the mediation effect was estimated as the product of the first 2 relationships. Then we applied the percentile bootstrap method to obtain the 95% CI for the estimate of mediation effect. RESULTS: Number of frailty conditions and episodes of absolute change >15% in fractional MAP were inversely proportional. Presence of ≥4 frailty conditions was associated with >40% reduction of the number of episodes of absolute change >15% in fractional MAP. Regarding mortality, episodes of absolute change >15% in fractional MAP were protective. The addition of absolute change >15% in fractional MAP in the mortality model resulted in a decrease in the frailty odds ratio from 10.6 to 9.1 (4+ conditions), suggesting that episodes of absolute change >15% in fractional MAP are indeed a mediator. The mediation effect was modest; 5 episodes of absolute change >15% in fractional MAP was 5.2%, 6.4%, 6.9%, and 9.0% for frailty conditions from 1 to 4+, respectively. CONCLUSIONS: Frailty is associated with less intraoperative blood pressure variation, and the relationship of frailty with 30-day mortality is partially mediated by episodes of absolute change >15% in fractional MAP. This suggests that autonomic dysregulation may be a modest part of the mechanism behind the association between frailty and perioperative mortality. Our finding is consistent with recent literature, suggesting that an intact autonomic nervous system confers lower perioperative mortality. Accepted for publication January 16, 2019. Funding: This work was supported by National Institute on Aging (K23 AG17-015; S.G.D.), Optimizing Postoperative Cognition in the Elderly, (American Federation of Aging Beeson Scholar Program; S.G.D.), and the American Federation for Aging Research, Medical Student Training in Aging Research (L.A.J.). Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Stacie G. Deiner, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, c/o S Deiner, Box 1010, 1 Gustave L. Levy Pl, New York, NY 10029. Address e-mail to stacie.deiner@mssm.edu. © 2019 International Anesthesia Research Society

https://ift.tt/2EDvh7w

Use of Preoperative Salivary Cortisol AM/PM Ratio for Prediction of Early Postoperative Cognitive Dysfunction

No abstract available

https://ift.tt/2EFdOLW

Long Intravascular Persistence of 20% Albumin in Postoperative Patients

BACKGROUND: Albumin may persist intravascularly for a shorter time in patients after major surgery than in healthy volunteers due to a surgery-induced breakdown (shedding) of the endothelial glycocalyx layer. METHODS: In this nonrandomized clinical trial, an IV infusion of 3 mL/kg of 20% albumin was given at a constant rate during 30 minutes to 15 patients on the first day after major open abdominal surgery (mean operating time 5.9 h) and to 15 conscious volunteers. Blood samples and urine were collected during 5 h and mass balance calculations used to estimate the half-lives of the administered albumin molecules and the induced plasma volume expansion, based on measurements of hemodilution and the plasma albumin concentration. RESULTS: At the end of the infusions, albumin had diluted the plasma volume by 13.3% ± 4.9% (mean ± SD) in the postoperative patients and by 14.2% ± 4.8% in the volunteers (mean difference −0.9, 95% CI, −4.7 to 2.9; 1-way ANOVA P = .61), which amounted to twice the infused volume. The intravascular half-life of the infused albumin molecules was 9.1 (5.7–11.2) h in the surgical patients and 6.0 (5.1–9.0) h in the volunteers (Mann-Whitney U test, P = .26; geometric mean difference 1.2, 95% CI, 0.8–2.0). The half-life of the plasma volume expansion was 10.3 (5.3–17.6; median and interquartile range) h in the surgical patients and 7.6 (3.5–9.0) h in the volunteers (P = .10; geometric mean difference 1.5, 95% CI, 0.8–2.8). All of these parameters correlated positively with the body mass index (correlation coefficients being 0.42–0.47) while age and sex did not affect the results. CONCLUSIONS: Twenty percent albumin caused a long-lasting plasma volume expansion of similar magnitude in postoperative patients and volunteers. Accepted for publication December 28, 2018. Funding: The study was supported by a grant from Mats Kleberg Foundation. The authors declare no conflicts of interest. ClinicalTrials.com, identifier NCT02556580. Reprints will not be available from the authors. Address correspondence to Robert G. Hahn, MD, PhD, Research Unit, Södertälje Hospital, 152 86 Södertälje, Sweden. Address e-mail to r.hahn@telia.com. © 2019 International Anesthesia Research Society

https://ift.tt/2VxEtjz

Severe asthma in children: therapeutic considerations

Purpose of review Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring and a detailed multidisciplinary team assessment to identify modifiable factors contributing to poor control is needed prior to considering therapy escalation. Pathophysiological phenotyping in those with true severe therapy-resistant asthma (STRA) and the current array of add-on therapies will be discussed. Recent findings Adherence monitoring using electronic devices has shown that only 20–30% of children with PSA have STRA and need additional therapies. Omalizumab and mepolizumab are licensed for children with STRA aged 6 years and older. Although robust safety and efficacy data, with reduced exacerbations, are available for omalizumab, biomarkers predicting response to treatment are lacking. Paediatric safety data are available for mepolizumab, but efficacy data are unknown for those aged 6–11 years and minimal for those 12 years and older. A sub-group of children with STRA have neutrophilia, but the clinical significance and contribution to disease severity remains uncertain. Summary Most children with PSA have steroid sensitive disease which improves with adherence to maintenance inhaled corticosteroids. Add-on therapies are only needed for the minority with STRA. Paediatric efficacy data of novel biologics and biomarkers that identify the optimal add-on for each child are lacking. If we are to progress toward individualized therapy for STRA, pragmatic clinical trials of biologics in accurately phenotyped children are needed.

https://ift.tt/2NzlrGG

Editorial introductions

No abstract available

https://ift.tt/2GS8tmT

Contributions of innate lymphocytes to allergic responses

Purpose of review Allergic diseases represent a growing global health concern, especially among pediatric populations. Current strategies for the treatment of allergies and asthma focus on limiting the severity of the symptoms; however, additional research investigating the mechanisms promoting inflammation in the context of allergic reactions may lead to the development of more effective therapeutic strategies. Recent findings Novel studies have highlighted the contributions of innate lymphocytes to the induction of inflammatory responses to allergens. Remarkably, neuron-derived signals, hormones, and even vitamins have been suggested to modulate the activity of innate lymphocytes, opening new windows of opportunity for the treatment of allergic inflammation. Summary These studies highlight the complex interactions of the nervous, endocrine, and immune system that promote pathology in the context of allergic inflammation. Further studies are required to understand these interactions in order to aid in the development of novel and much-needed therapies to treat allergic conditions.

https://ift.tt/2NCheSl

Neutrophil activation in occupational asthma

Purpose of review The aim of this review is to emphasize the role of neutrophils in patients with occupational asthma. This review facilitates a better understanding, accurate diagnosis, and proper management of asthmatic reactions provoked at the workplace. Recent findings Increased recruitment and infiltration of neutrophils are found in patients with occupational asthma. Activated neutrophils release several mediators including pro-inflammatory cytokines and extracellular traps, leading to stimulation of airway epithelium and other inflammatory cells. Summary New insights into neutrophils in the pathogenesis of occupational asthma may provide a novel approach to the individual patient with occupational asthma.

https://ift.tt/2GS7vqu

Phenotypes of wheezing and asthma in preschool children

Purpose of review The purpose of this review is to provide an overview of the identified phenotypes of preschool wheezing. Recent findings Early life wheezing patterns have been described in multiple populations, with several commonalities found between cohorts. Early life environmental exposures have been found to be differentially associated with preschool wheezing phenotypes and their future trajectories. These include allergen and microbe exposure, environmental tobacco smoke exposure, and maternal stress and depression. Elevated IgE in early life may also influence future asthma risk. Summary Preschool wheezing phenotypes are heterogeneous and complex, with trajectories that are related to factors including environmental exposures. More research is needed to characterize these relationships, hopefully leading to targeted prevention strategies.

https://ift.tt/2NzlJNM

Impact of occupational exposure on human microbiota

Purpose of review Recent evidence suggests that environmental exposures change the adult human microbiome. Here, we review recent evidence on the impact of the work microbiome and work-related chemical, metal and particulate exposures on the human microbiome. Recent findings Prior literature on occupational microbial exposures has focused mainly on the respiratory effects of endotoxin, but a recent study suggests that not all endotoxin is the same; endotoxin from some species is proinflammatory, whereas endotoxin from other species is anti-inflammatory. Work with animals can change the adult human microbiome, likely through colonization. Early studies in military personnel and animal models of gulf war illness show that military exposures change the gut microbiome and increase gut permeability. Heavy metal and particulate matter exposure, which are often elevated in occupational settings, also change the gut microbiome. Summary An emerging body of literature shows that work-related exposures can change the human microbiome. The health effects of these changes are currently not well studied. If work exposures lead to disease through alterations in the human microbiome, exposure cessation without addressing changes to the human microbiome may be ineffective for disease prevention and treatment.

https://ift.tt/2GO9MmE

Basophil activation testing in occupational respiratory allergy to low molecular weight compounds

Purpose of review There is an unmet need for better immunological tests in cases of suspected occupational asthma to many workplace chemicals; here we consider the basophil activation test (BAT), a potential alternative to the detection of specific IgE antibodies. Recent findings BAT is fairly widely used in general allergy services; and there is increasing experience of its use in the diagnosis of occupational allergy to low molecular weight agents and chemicals including wood dusts, persulphates, antibiotics and latex. Summary There is potential for BAT to become a useful tool in the clinical consideration of occupational asthma and of its mechanisms, and even to take a place in a Bayesian-based diagnostic algorithm. Further development will only occur if specialist centres with appropriate facilities, and preferably in collaboration, contemplate its use.

https://ift.tt/2GSnGnJ

Preventing the development of asthma: stopping the allergic march

Purpose of review To describe important precipitants of asthma and allergic disease, to highlight the links between these triggers and modifications within the immune system, and to examine innovative research regarding asthma prevention with focus on attenuating the atopic march. Recent findings Allergen avoidance, allergen immunotherapy, IgE antagonists, prevention and treatment of respiratory infections, as well as management of gastrointestinal and respiratory dysbiosis have been considered as strategies in asthma prevention. Antenatal vitamin D supplementation in expectant mothers and aggressive control of atopic dermatitis to prevent the development of other allergic conditions were carefully studied as well. Summary Asthma is a major cause of morbidity and lost productivity. Despite the tremendous burden of this disease, the scientific community is still struggling to find an effective means of prevention. The contribution of genetics to the development of atopy cannot be altered, but environmental changes as well as pharmacotherapy have been studied as modifiable risk factors. Many trials to date have been effective only for subjects with certain characteristics. This is likely because asthma is a heterogenous condition, with a variety of triggers and clinical phenotypes. Thus far, a universally effective prevention strategy has eluded us. However, if an intervention can be found to prevent asthma and the allergic march, it will greatly improve quality of life for millions of sufferers and decrease healthcare expenditures.

https://ift.tt/2NzNQMN

Use of population data for assessing trends in work-related asthma mortality

Purpose of review Work-related asthma has been associated with poorer asthma control and frequent unscheduled healthcare visits, and can be fatal. Case reports of work-related asthma deaths are rare, but can initiate efforts to prevent additional cases. We reviewed relevant literature and data sources to evaluate whether analyzing mortality data at the population level can help identify potential sources of exposures that contribute to work-related asthma. Recent findings A limited number of population-based studies have addressed work-related asthma mortality. Data on asthma mortality are derived from death certificates using the International Classification of Diseases (ICD) as a standard for coding cause. However, no discrete code for work-related asthma is available. Analysis of asthma mortality relative to industries and occupations appears to identify high-risk jobs that were not identified by analyzing asthma morbidity data. Summary Beyond recognized work-related asthma deaths, it is possible that occupational exposures have contributed to other asthma deaths that have gone unnoticed and could potentially be identified by the analysis of mortality data at the population level. Such analyses in the United States appear to assist in recognizing high-risk occupations and industries. Additional analyses would be possible if a work-related asthma ICD code were available.

https://ift.tt/2NCh0KZ

Diagnosis of occupational hypersensitivity pneumonitis

Purpose of review To discuss the diagnostic methods currently used in the study of patients with hypersensitivity pneumonitis, with special emphasis on the most recent contributions published in the medical literature regarding the diagnosis of occupational hypersensitivity pneumonitis (OHP). This review presents an update of the use of these diagnostic tests, a controversial issue among experts. Recent findings In spite of the multiple attempts at systematization and the publication of expert consensus statements, standardizing and diagnostic methods and criteria remain particularly difficult. As a result, centers tend to rely on their own experience and establish diagnosis by consensus among their multidisciplinary teams. Though recommendable in many ways, this method presents significant limitations. Summary Diagnosis of OHP should be made with a thorough clinical history of the symptoms and clinical signs as well as a meticulous review, if possible by an expert, of possible exposures in the working environment; a meticulous physical examination; high-resolution computed tomography of the thorax; serum determination of specific immunoglobuline Gs; bronchoalveolar lavage and possibly cryobiopsy; fungal culture; and, when appropriate, a specific inhalation challenge test with the suspected antigen.

https://ift.tt/2NBwgrB

Precision medicine in childhood asthma

Purpose of review Childhood asthma is a heterogeneous disease and many children have uncontrolled disease. Therefore an individualized approach is needed to improve asthma outcomes in children. Precision medicine using clinical characteristics, biomarkers, and the rapidly involving field of genomics and pharmacogenomics aims to achieve asthma control and reduce future risks with less side-effects in individual children with asthma. Recent findings It is not yet possible to select treatment options on clinical characteristics. Novel monoclonal antibodies are efficacious in patients with severe, eosinophilic asthma. Reduced lung function growth and early decline is a prevalent finding in children with persistent asthma. Pharmacogenetic studies have identified children at risk for cortisol suppression when using inhaled corticosteroids. Summary Clinical characteristics and simple biomarkers like eosinophils, IgE, and the fraction of exhaled nitric oxide may be used in clinical practice for a basic precision medicine approach, deciding which children will have the best chance to respond to inhaled corticosteroids and to the biologicals omalizumab and mepolizumab. Further application of pharmacogenomics and breathomics needs additional studies before they can be applied as tools for precision medicine in individual children with asthma.

https://ift.tt/2GQTY2A

Single inhaler maintenance and reliever therapy in pediatric asthma

Purpose of review Asthma affects more than 25 million people worldwide and continues to grow in prevalence. According to a center for disease control and prevention (CDC) report, the total annual cost of asthma in the United States between 2008 and 2013, including medical care, absenteeism, and mortality, was $81.9 billion. Although the National Institute of Health guidelines recommend fixed inhaled corticosteroid (ICS) dosing, the 2008–2010 Medical Expenditure Panel Survey showed that asthma is still poorly controlled. Single inhaler maintenance and reliever therapy (SMART) offers a possible alternative management plan. This is a review of SMART vs. current treatment guidelines. Recent findings SMART addresses variable inflammation with symptom-driven dosing of ICS. It relies on a combination inhaler that has a long-acting β-agonist, which has an immediate onset of action to provide quick relief, in combination with an ICS. Recent studies show that SMART decreases the frequency and severity of asthma exacerbations when compared to fixed ICS dosing. In addition, intermittent use of ICS gave a reduced effect on growth and permitted a lower total amount of ICS to be delivered. Summary SMART appears to outperform treatment that is based on current guidelines in the United States. As inhalers capable of being used for SMART are already approved, what is needed is Food and Drug Administration approval of the SMART strategy.

https://ift.tt/2NBw6jZ

Management of acute loss of asthma control: yellow zone strategies

Purpose of review Asthma exacerbations are associated with a significant burden to both the individual patient and to the healthcare system. Patients often step-up home therapies in response to increased asthma symptoms, and the asthma action plan was created to empower patients to self-manage their asthma care. The yellow (intermediate) zone of the asthma action plan is frequently poorly defined, and current Expert Panel Report 3 guideline recommendations are not effective for all patients. This article reviews the evidence behind various recommended yellow zone intervention strategies. Recent findings There are many potential methods of delivering yellow zone therapy, and recent studies have assessed preventive efficacy of a scheduled increase in controller medication(s), reliever medication(s), or a symptom-driven combination of both. The literature suggests that, in certain asthma subpopulations, some methods may be more efficacious than others. Summary Multiple yellow zone approaches may be beneficial, and the yellow zone is not a 'one size fits all' narrative.

https://ift.tt/2GS7fYy

The impact of exercise on asthma

Purpose of review Asthma is one of the most common chronic diseases in children and adults in developed countries around the world. Despite international treatment guidelines, poor asthma control remains a frequent problem leading to missed school and work, and emergency room visits and hospitalizations. Many patients with asthma report exercise as a trigger for their asthma, which likely leads to exercise avoidance as a means to control symptoms. Evolving research has suggested that routine exercise may actually help improve some aspects of asthma control. This review discusses the recent research addressing how routine exercise affects important asthma-related outcomes including symptoms, lung function and quality of life. Recent findings Several systematic reviews and meta-analyses have been conducted in recent years, which strongly support the safety of routine exercise in children and adults with asthma. Exercise appears to favor improvements in aerobic fitness, asthma symptoms and quality of life, but results so far are less consistent in demonstrating improvements to lung function and airway hyperresponsiveness. Summary In addition to routine management guidelines, clinicians should recommend for their patients with asthma routine exercise for its general health benefits and likely improvement in asthma symptoms and quality of life.

https://ift.tt/2NBvOJV

Symptom-based patient-reported outcomes in adults with eosinophilic esophagitis: value for treatment monitoring and randomized controlled trial design

Purpose of review In adults with eosinophilic esophagitis (EoE), a chronic, inflammatory immune-mediated condition of the esophagus, both inflammation and fibrosis are likely associated with symptom generation. Therefore, assessing symptom-based patient-reported outcomes (PROs), defined by US Food and Drug Administration as 'any report of the status of a patient's health condition that comes directly from the patients, without interpretation of the patient's response by a clinician or anyone else', is important in the context of trials and observational studies of emerging therapies. Recent findings For purposes of treatment monitoring, lack of symptoms does not predict the absence of biologic inflammation; hence, endoscopy with esophageal biopsies should be performed to check for residual inflammation. Lack of inflammation does not predict lack of symptoms, and the presence of subepithelial fibrosis cannot be excluded. No published instrument currently measures the frequency of dysphagia described all possible ways, strategies of living with this symptom and various pain types. In randomized controlled trials, in which symptom response was detected using validated PRO measures, only modest decreases in symptom scores were observed. Summary Accessing full EoE symptom spectrum and optimizing PRO measures remains a challenge that should be tackled to reliably assess response to existing and emerging therapies.

https://ift.tt/2GSz7fr

Vitamin D and childhood asthma: causation and contribution to disease activity

Purpose of review To review the literature of the past 18 months (April 2017 through September, 2018) relating to vitamin D and childhood asthma. Recent findings A combined analysis of two clinical trials of maternal vitamin D supplementation trials showed a significant protective effect of vitamin D supplementation trials in the primary prevention of asthma and recurrent wheeze up to age 3 years. Secondary analyses from these trials have also suggested that initial maternal vitamin D status could affect the response to supplementation during pregnancy, with the biggest protective effect in children born to mothers with initial 25hydroxyvitamin D (25OHD) levels of at least 30 ng/ml. A postnatal, 6-month vitamin D supplementation trial in black, premature babies showed a 34% decreased risk of recurrent wheezing at 1 year among the infants who received supplementation. An individual patient data meta-analysis of published clinical trials concluded that vitamin D supplementation decreased the risk of asthma exacerbations in those with 25OHD levels less than 10 ng/ml. Results of observational analyses on primary prevention of asthma and in prevention of exacerbations remain mixed, with the bulk of the evidence suggesting that there is a protective effect of higher vitamin D levels. Summary Evidence continues to accumulate that vitamin D supplementation helps to prevent the development of asthma and recurrent wheeze in early life, and may also help in the management of asthma. The level(s) of circulating vitamin D that maximizes these effects remains to be identified.

https://ift.tt/2NAzX0P

How guideline can shape clinical practice globally: the diagnosis and rationale for action against cow's milk allergy experience

Purpose of review Allergic diseases are increasing worldwide and are considered an important public health problem causing severe and even life-threatening reactions. The creation of guidelines aims to help clinicians improving the quality of diagnosis and management of such diseases. Clinical practice guidelines alone are not sufficient and there is a need for implementation strategies for their introduction into daily practice. We report here the main international allergy guidelines with a more focused look on the Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines and their effect on clinical practice. Recent findings DRACMA guidelines have clearly modified the approach to cow's milk allergy (CMA) from its diagnosis to treatment tailoring the choices for each patient. Although they strongly recommend oral food challenge for diagnosing CMA, they also indicate that it may not be necessary in many cases with the introduction of the pretest probability of CMA. Studies on the implementation of DRACMA guidelines show how they influenced the formula market, making appropriate treatments more affordable. Summary DRACMA reconciled international differences in the diagnosis and management of CMA. They introduced the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology in the field of food allergy and highlighted the importance for meta-analyses to be able to adapt recommendations to the local context.

https://ift.tt/2GSn9Cf

Making Decisions Together

I love working with kids. It's one of the reasons I got into this gig, and it makes the day...

https://ift.tt/2TmwVlX

The Whole Ball of Wax: A Longer Than Normal Post About Your Cerumen

"But what do I do with my ear wax?" says the man in my chair, a fully grown man who...

https://ift.tt/2IID7AU

What’s the Difference Between Pediatric Dentistry & Orthodontics?

While closely related, pediatric dentistry & orthodontics are not the same. In this video, Dr. Emily Hahn explains why your pediatric dentist might recommend that your child see an orthodontist. Learn the age at which the American Academy of Orthodontics recommends that every child see an orthodontist. Also, find out why braces may not be right for all young children.

The post What's the Difference Between Pediatric Dentistry & Orthodontics? appeared first on ChildrensMD.

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Restoring Blood Supply to the Heart While Replacing the Lungs: Is It Worth the Risk?

No abstract available

https://ift.tt/2tJnJKg

Inhibition of Cyclin-dependent Kinase 2 Signaling Prevents Liver Ischemia and Reperfusion Injury

Background: Liver ischemia and reperfusion injury (IRI) is a major complication of liver transplant, hepatectomy, and hemorrhagic shock. The cyclin-dependent kinase 2 (CDK2) acts as a pivotal regulator of cell cycle and proliferation. Methods: This study evaluated the modulation and therapeutic potential of CDK2 inhibition in a mouse model of partial liver warm IRI. Results: Liver IR triggered intrinsic CDK2 expression, peaking by 0.5h of reperfusion, and maintaining a high level throughout 1h-24h. Roscovitine, a specific CDK2 inhibitor, prevented liver IR mediated damage with abolished serum ALT levels and reserved liver pathology. CDK2 inhibition mediated liver protection was accompanied by decreased macrophage/neutrophil infiltration, diminished hepatocyte apoptosis, abolished TLR4 signaling and downstream gene inductions (CXCL-10, TNF-a, IL-1β and IL-6), yet augmented IL-10 expression. In vitro, CDK2 inhibition by Roscovitine suppressed macrophage TLR4 activation, and further depressed downstream inflammatory signaling (MyD88, IRF3, p38, JNK and ERK). Conclusions: Our novel findings revealed the critical role of CDK2 in hepatic cytoprotection and homeostasis against liver IRI. As CDK2 inhibition regulated local immune response and prevented hepatocyte death, this study provided the evidence for new treatment approaches to combat IRI in liver transplant. * These authors contributed equally to this work Disclosure: The authors declare no conflicts of interest. Funding: NIH Grant R21 AI122155 and AI138165 (HJ). PO1 AI120944, RO1 DK107533, DK102110, and DK062357 (JWKW). The Dumont Research Foundation. Correspondence Information: Haofeng Ji, MD. Dumont-UCLA Transplant Center, 77-120 CHS, 10833 Le Conte Ave, Los Angeles, CA 90095. Phone: (310) 206-0328; Fax: (310) 267-2367; Email: hji@mednet.ucla.edu. Jiamin Zhang, MD. 228 Xinhua st, Jinhua, Zhejiang, China, 321000. Email: zjm0323001@126.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Immune Cell Trafficking to the Liver

The human liver is an organ with a diverse array of immunologic functions. Its unique anatomic position that leads to it receiving all the mesenteric venous blood, combined with its unique micro anatomy, allows it to serve as a sentinel for the body's immune system. Hepatocytes, biliary epithelial cells, Kupffer cells, stellate cells, and liver sinusoidal endothelial cells express key molecules that recruit and activate innate and adaptive immunity. Additionally, a diverse array of lymphoid and myeloid immune cells resides within and traffics to the liver in specific circumstances. Derangement of these trafficking mechanisms underlie the pathophysiology of autoimmune liver diseases, NASH, and liver transplantation. Here, we review these pathways and interactions along with potential targets that have been identified to be exploited for therapeutic purposes. Disclosure: AG receives research support from United Therapeutics. SC and JE have no conflicts of interest to report. Funding: SC received support from the NIH 5T32HL007854-19 grant. AG was supported by the Louis J. Gerstner, Jr. Foundation Award and the American Association for the Study of Liver Diseases Career Development Award in the Memory of the University of Michigan Transplant Team, NIH-NIAID R56 AI122332 and by the National Center for Advancing Translational Sciences, National Institutes of Health through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Adam Griesemer, MD, Department of Surgery, Columbia University Medical Center, 622 West 168th Street, Floor 14, New York, NY 10032, Tel: 212-305-9691, Fax: 212-342-5600, Email: adg2101@cumc.columbia.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Clinical significance of alloantibodies in hand transplantation – a multicenter study

Background: Donor-specific antibodies (DSA) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. Methods: We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. Results: Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first three post operative years). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. Conclusions: While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring and the relevance of an HLA class II match in UET recipients. Funding: The study was supported by Emil and Vera Cornell's Foundation, Stig and Gunborg Westman's Foundation, The Foundation Blanceflor Boncompagni Ludovisi née Bildt, the Hirsch Fellowship for Surgeons, Erik and Edith Fernström´s Foundation for Medical Research, and the Swedish Society of Medicine. Disclosure: The authors declare no conflicts of interest. *Corresponding author: Erik Berglund, M.D., Ph.D. , Division of Transplantation Surgery, CLINTEC, Karolinska Institute, and Department of Transplantation Surgery, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. Email: Erik.Berglund@ki.se Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Glass Slippers and Glass Cliffs: Fitting in and Falling Off

Background: A 'glass-ceiling' effect exists for women in male-dominated professions. Recent studies also show a 'glass-cliff' effect where senior women can more easily fall from positions of leadership. Transplantation remains a male-dominated specialty. This study investigated gender and the perception of adverse clinical incidents in transplantation. Methods: Web-based survey involving five clinical scenarios which described errors or mistakes with male or female named protagonists. Questionnaires allocated at random. To address unconscious bias, the study was described as examining 'actions following clinical adverse incidents in transplantation'. Each scenario was followed by two closed questions (i) clinical performance rating (ii) selection of action required. Reasoning was invited (open text comments). Responses were analysed using quantitative and qualitative methods. Results: 191 invitees responded; 134 completed questionnaires. Total responses showed no differences (P>0.05) in performance ratings, although for 'first solo laparoscopic surgery' scenario some indication 'No Action' more likely if surgeon male (P=0.056). Male responses rated female performance as significantly worse (P=0.035) for the laboratory-based scenario. 102 participants provided open text comments. Thematic analysis identified seven themes. 'Acceptable levels of risk' theme demonstrated engendered leadership beliefs i.e. when 'clinical judgement' proved incorrect, males described as 'forceful' but females as 'needing support'. In cases where things went wrong, respondents were more likely to comment females should not have decided to proceed. Conclusion: While gender may no longer be an overt issue in perceived performance of senior staff in transplantation, respondents' use of language and their choice of words display elements of unconscious (covert) engendered views. Financial disclosure: Coventry Kidney Research Fund – Support towards funding statistical work. LINC Medical Systems Ltd, U.K- Support towards funding statistical work. Conflicts of interest: None. Corresponding Author: Nithya Krishnan, FRCP, MD, Renal Unit, University Hospitals Coventry & Warwickshire NHS Trust, Coventry, UK. Email: nithya.krishnan@uhcw.nhs.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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The Promise of Single Kidney Transplants from Small Pediatric Donors

No abstract available

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Patterns and Predictors of Mortality after Waitlist Dropout of Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation

Background: There is a lack of information about survival after dropout from the liver transplant waiting list. Therefore, we aimed to assess the overall survival, and risk factors for death, after waiting list dropout due to hepatocellular carcinoma (HCC) progression. Methods: We assessed patients who dropped out of the liver transplant waiting list between 2000 to 2016 in a single, large academic North-American center. Patients were divided into 3 groups according to the type(s) of HCC progression: locally advanced disease (LAD), extrahepatic disease (EHD), and macrovascular invasion (MVI). The primary outcome was overall survival. Survival was assessed by the Kaplan-Meier method. Predictors of death after dropout were assessed by multivariable Cox regression. Results: During the study period, 172 patients dropped out due to HCC progression. Of those, 37 (21.5%), 74 (43%) and 61 (35.5%) dropped out due to LAD, EHD and MVI, respectively. Median survival according to cause of dropout (LAD, EHD or MVI) was 1.0, 4.4 and 3.3 months, respectively (P = .01). MELD score [HR = 1.04, 95%CI, 1.01-1.08)], alcoholic liver disease [HR = 1.66 (95%CI 1.02-2.71), and alpha fetoprotein >1000 ng/mL [HR = 1.86 (95%CI 1.22-2.84)] were predictors of mortality after dropout. Dropout due to EHD [HR = 0.61 (95%CI 0.38-0.98)] and undergoing treatment after dropout were protective factors [0.32 95%CI 0.21-0.48)] for death. Conclusion: Patient prognosis after dropout is dismal. However, a subgroup of patients may have longer survival. The present study identifies the patterns of waitlist dropout in patients with HCC and provides evidence for the effectiveness of treatment strategies offered to HCC patients after dropout. * Andre Gorgen and Roizar Rosales contributed equally to this work. Conflicts of Interest: None to declare Financial support: None Address for correspondence: Dr. Gonzalo Sapisochin, Assistant Professor of Surgery, University of Toronto, Staff Surgeon, HBP & Multi Organ Transplant Program, Division of General Surgery. University Health Network, 585 University Avenue, 11PMB184, Toronto, M5G 2N2, ON, Canada,. T : +1 416 340 4800 ext. 5169 / F : +1 416 340 3237 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Ex Situ Machine Perfusion of Human Donor Livers via the Surgically Reopened Umbilical Vein: A Proof of Concept

Background: Machine perfusion of donor livers is typically performed via the portal vein main stem. Instead, cannulation of a reopened umbilical vein could allow machine perfusion during organ procurement and subsequent implantation in the recipient without interruption of the portal venous circulation. We aimed to assess the feasibility of portal venous machine perfusion via the umbilical vein. Methods: During back table inspection of five human livers declined for transplantation, the umbilical vein was surgically reopened, dilated and cannulated. Hypothermic and normothermic oxygenated machine perfusion (NMP) were performed using the umbilical vein for portal inflow. Three livers were perfused with hypothermic machine perfusion, one full liver graft underwent NMP for four hours, and one left lateral split procedure was performed under continuous NMP with portal perfusion via the umbilical vein. Results: In all livers access to the portal venous system via the umbilical vein was successfully achieved, with good portal flows and macroscopically homogeneous perfusion. The full liver graft that underwent NMP via the umbilical vein for four hours showed good lactate clearance, normalized pH and achieved good bile production with pH >7.55. During the split procedure under continuous NMP via the umbilical vein, the left lateral segment and extended right lobe remained equally perfused, as demonstrated by Doppler-ultrasound. Conclusion: Machine perfusion with portal perfusion via the umbilical vein is feasible. Portal venous flows were similar to those obtained after cannulation of the portal vein main stem. This technique enables continuous oxygenated perfusion of liver grafts during procurement, splitting and implantation. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Conflicts of interest: The authors have no conflicts of interest to declare. Financial disclosure: No funding was obtained for this study. Corresponding Author: Vincent de Meijer, MD, PhD, Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Tel.: +31503612896 / Fax: +31 50 361 4873 Email: v.e.de.meijer@umcg.nl Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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What is Hot and New in Basic Science in Liver Transplantation in 2018? Report of the Basic Science Committee of the International Liver Transplant Society.

No abstract available

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Risk Indices in Deceased Donor Organ Allocation for Transplantation: Review From an Australian Perspective

Over the last decade, organ donation and transplantation rates have increased in Australia and worldwide. Donor and recipient characteristics for most organ types have generally broadened resulting in the need to consider more complex data in transplant decision-making. As a result of some of these pressures, the Australian software used for donor and recipient data management is currently being updated. Because of the in-built capacity for improved data management, organ allocation processes will have the opportunity to be significantly reviewed, in particular the possible use of risk indices to guide organ allocation and transplantation decisions. We aimed to review risk indices used in organ allocation policies worldwide and to compare their use to current Australian protocols. Significant donor, recipient and transplant variables in the indices were summarized. We conclude that Australia has the opportunity to incorporate greater use of risk indices in its allocation policies and in transplant decision-making processes. However, while risk indices can assist with organ allocation and help guide prognosis, they often have significant limitations which need to be properly appreciated when deciding how to best use them to guide clinical decisions. Disclosure: The authors declare no conflicts of interest. Funding: No funding was received for the paper. Corresponding Author: Jonathan Eng Ho Ling, Nephrology Unit, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168., Email: Jonathan.ling@monash.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Coronary Artery Disease and Coronary Artery Bypass Grafting at the Time of Lung Transplantation Do Not Impact Overall Survival

Background: Coronary artery disease (CAD) is common in lung transplant candidates and may require revascularization before or at the time of their transplant. We reviewed the survival of lung transplant recipients with coronary artery disease requiring surgical intervention (CAD-CABG) and those who did not (CAD-NoCABG) at the time of transplant, compared to a cohort with no CAD (NoCAD). Methods: We conducted a retrospective cohort study of adult patients transplanted in our program between 2004-2013. Our primary outcome was the association between 3-way CAD status (CAD-CABG, CAD-NoCABG, NoCAD) and overall retransplant-free survival via proportional hazards modelling, adjusting for age, gender and transplant indication. Secondary endpoints included 1-year survival, survival by Kaplan-Meier analysis, duration of ventilation, ICU stay and hospitalization. Results: 333 patients underwent transplant during the study timeframe. 24 (7%) had CAD requiring CABG, 82 (25%) had CAD not requiring CABG and the remaining 227 had no CAD. 3-way CAD status was not associated with overall retransplant-free survival after adjustment for age, gender and transplant indication. Duration of mechanical ventilation, ICU stay and hospitalization were longer in both CAD groups compared to the NoCAD group. Conclusions: CAD status does not impact overall retransplant-free survival, despite greater perioperative complexity. Prospective studies comparing treatment strategies in these patient groups are warranted. DISCLOSURE: The authors of this manuscript have no disclosures of note. This study was unfunded. We acknowledge the University of Alberta Hospital and Alberta Health Services for use of resources. Corresponding Author: Kieran Halloran, MD, University of Alberta, 11350 83rd Street, 3-125 Clinical Sciences Building, Edmonton, Alberta, Canada T6G2G3, Telephone: 1-780-492-2691 Fax: 1-780-492-4483, Email: kieran.halloran@ualberta.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Mesenchymal Stem Cell Therapy in Submandibular Salivary Gland Allotransplantation: Experimental Study

Background. Allotransplantation of submandibular salivary glands (SMGs) could be an alternative treatment option for severe keratoconjunctivitis sicca in non-candidates for autologous submandibular salivary gland transplantation. This study was conducted to evaluate the effect of allogeneic mesenchymal stem cell (MSC) therapy on the survival of allotransplanted SMGs. Methods. Thirty-six SMG allotransplantations (n = 6 per group) were performed in New Zealand white (NZW) rabbits and randomly divided into the following groups: Allograft control (Allo-Ctrl), low dose FK506 (FK506-L), high dose FK506 (FK506-H), allogeneic MSCs, MSCs+FK506-L, and MSCs+FK506-H. Rabbits were closely observed for two weeks. Gland viability and rejection were assessed by monitoring interleukin-2 (IL-2) levels by enzyme-linked immunosorbent assay (ELISA), sialoscintigraphy, M3-muscarinic acetylcholine receptor (M3 receptor) expression, histological evaluation, and apoptosis assay. Results. Intraoperatively, all glands showed patency and saliva flow except one gland. Sialoscintigraphy revealed significantly higher saliva production within the MSC-treated glands. Histologically, MSC-treated glands showed higher glandular tissue preservation and less acini atrophy. MSCs+FK506-H group revealed significantly lower apoptosis percentage. The highest survival was observed in the MSCs+FK506-H, followed by the FK506-H and MSCs+FK506-L, and lastly less in the FK506-L and MSCs groups. Conclusions. Concurrent administration of MSCs with FK506-H (0.16 mg/kg) resulted in higher survival rate with greater glandular tissue preservation and salivary secretion. MSCs with FK506-L (0.08 mg/kg) could be an alternative to FK506-H (0.16 mg) in salivary gland allotransplantation. IACUC approval: The study was approved by the Institutional Animal Care and Use Committee (IACUC) (SNU-160720-6-2) Disclosure: The authors declare no conflicts of interest. Funding: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI15C1535). Corresponding author: Jong-Ho Lee, DDS, MSD, PhD, Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, 275-1, Yeongun-Dong, Chongro-Ku, Seoul, 110-768, Korea. leejongh@snu.ac.kr, Phone +82-2-2072-2630, Mobile +82-10-3772-7353, Fax +82-2-766-4948 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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