Background The aim of this study is to report the experience with a program of Intensive Care to facilitate Organ Donation (ICOD) in 2 Spanish centers based on a common protocol. Methods Retrospective review of clinical charts of patients with a devastating brain injury whose families were approached to discuss the possibility of ICOD once further treatment was deemed futile by the treating team. Study period: 1/1/2011-12/31/2015. Results ICOD was discussed with families of 131 patients. Mean age of possible donors was 75 (SD=11) years. The main cause of brain injury was an intracranial hemorrhage (72%). Interviews with families were held after the decision had been made not to intubate/ventilate in 50% of cases, and after the decision not to continue with invasive ventilation in the remaining cases. Most interviews (66%) took place in the emergency department. The majority of families (95%) consented to ICOD. Of the 125 consented cases, 101 (81%) developed brain death (BD), most in ≤72 hours. Ninety-nine patients (98%) transitioned to actual donation after BD, with 1.2 organs transplanted per donor. Of patients who did not evolve to BD, 4 died following an unexpected cardiac arrest and 18 after the withdrawal of life-sustaining measures. ICOD contributed to 33% of actual donors registered at both centers. Conclusions ICOD is well accepted by families. Most patients evolve to BD within a short period of time. The practice substantially contributes to increasing organ donation and offers more patients the chance of donating their organs after death. CORRESPONDENCE INFORMATION: Beatriz Domínguez-Gil, MD, PhD. Director General, Organización Nacional de Trasplantes. C/Sinesio Delgado 6, pabellón 3, 28029 Madrid, Spain, Email: bdominguez@msssi.es AUTHORSHIP PAGE: FMS, JMPV and BDG conceived and designed the study. FMS, LMC and JMPV contributed with the data required for the study. EC and BDG coordinated the data collection and undertook the statistical analysis. JLM, AFC and PM participated in the performance of the research. FMS, JMPV and BDG drafted the first version of the paper, with contributions from the rest of the authors. The authors declare no conflict of interests. The study received no external funding. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2IWnX5J
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 4 Ιουλίου 2018
Donor Derived Viral Infections in Liver Transplantation
Donor-derived infections are defined as any infection present in the donor that is transmitted to 1 or more recipients. Donor-derived infections can be categorized into 2 groups: 'expected' and 'unexpected' infections. Expected transmissions occur when the donor is known to have an infection, such as positive serology for CMV, EBV or hepatitis B core antibody, at the time of donation. Unexpected transmissions occur when a donor has no known infection prior to donation, but 1 or more transplant recipients develop an infection derived from the common donor. Unexpected infections are estimated to occur in far less than 1% of solid organ transplant recipients. We will review the epidemiology, risk factors and approaches to prevention and management of donor-derived viral infectious disease transmission in liver transplantation. *Co-First Authors Corresponding Author: Michael G. Ison, MD MS FIDSA FAST, Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, 645 N Michigan Avenue Suite 900, Chicago, Illinois 60611, 312-695-4186 (Office), 312-695-5088 (Fax). mgison@northwestern.edu Authorship Page Hannah Nam, MD and Kathy M Nilles, MD are co-first authors. Both have made substantial contributions in gathering information necessary in drafting the article, participated in writing the article, and revised it critically for important intellectual content. Josh Levitsky, MD MS and Michael G Ison, MD MS have revised the article critically for important intellectual content and gave final approval of the version to be submitted, as well as any revised versions. Disclosures: HN and KMN have nothing to disclose. JL is a paid speaker for Gilead and Novartis. MGI has received support for research, paid to Northwestern University from Beckman Coulter, Cephied, Chimerix, Emergent BioScience, Gilead, Janssen, and Shire; compensated consultation from Chimerix, Celltrion, Genentech/Roche, MediVector, Seqirus, Shionogi, and VirBio; and paid membership of DSMB from GlaxoSmithKlein, Shionogi. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2KxdXFY
https://ift.tt/2KxdXFY
Incidence, Risk Factors and Outcomes of Early Acute Kidney Injury After Heart Transplantation: An 18-year Experience
Background Little is known about the incidence of acute kidney injury (AKI), as defined using the Kidney Disease Improving Global Outcome (KDIGO) classification, after heart transplantation (HT). Objective. Our objective was to evaluate the impact of AKI in a cohort of HT recipients. (Setting: University Hospital.) Methods We studied 310 consecutive HT recipients from 1999 to 2017, with AKI being defined according to the KDIGO criteria. Risk factors were analyzed by multivariable analyses, and survival by Kaplan-Meier curves and a risk-adjusted Cox proportional hazards regression model. Results 125 patients (40.3%) developed AKI, with 73 (23.5%), 18 (5.8%) and 34 (11%) patients having AKI stage 1, 2 and 3, respectively. Cardiac tamponade (OR: 16.82; 95% CI: 1.06–138), acute right ventricular failure (OR: 3.54; 95% CI: 1.82–6.88), and major bleeding (OR: 2.46; 95% CI: 1.18–5.1) were the principal risk factors for AKI. Patients with AKI had a greater hospital mortality (3.8% vs. 16%, P
https://ift.tt/2IUR8Ge
https://ift.tt/2IUR8Ge
Presence of gastric Helicobacter species in children suffering from gastric disorders in Southern Turkey
Helicobacter, EarlyView.
https://ift.tt/2lVOcQX
Targeting tumor-associated acidity in cancer immunotherapy
Abstract
Checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1) monoclonal antibodies have changed profoundly the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer, Hodgkin lymphoma, and bladder cancer. Currently, they are tested in various tumor entities as monotherapy or in combination with chemotherapies or targeted therapies. However, only a subgroup of patients benefit from checkpoint blockade (combinations). This raises the question, which all mechanisms inhibit T cell function in the tumor environment, restricting the efficacy of these immunotherapeutic approaches. Serum activity of lactate dehydrogenase, likely reflecting the glycolytic activity of the tumor cells and thus acidity within the tumor microenvironment, turned out to be one of the strongest markers predicting response to checkpoint inhibition. In this review, we discuss the impact of tumor-associated acidity on the efficacy of T cell-mediated cancer immunotherapy and possible approaches to break this barrier.
https://ift.tt/2Nt4Vr9
Early nonreactivity in the conjunctival provocation test predicts beneficial outcome of sublingual immunotherapy
Clinical practice needs a common parameter that can provide an early, reliable estimation of the outcome of sublingual immunotherapy (SLIT) in an upcoming pollen season. We investigated whether the conjunctiva...
https://ift.tt/2lUdCOz
A retrospective comparative study of endoscopic and microscopic Tympanoplasty
This study compares endoscopic and microscopic tympanoplasty for the treatment of chronic otitis media (COM) without cholesteatoma.
https://ift.tt/2tSJlV4
Total intravenous versus inhaled anesthesia in transsphenoidal tumor surgery
Visualization of the surgical field is essential for patient safety during endoscopic transsphenoidal tumor surgery. In this retrospective chart review and data analysis of patients undergoing endoscopic transsphenoidal resection of pituitary tumors under general anesthesia we sought to determine if total intravenous anesthesia with propofol and remifentanil leads to decreased bleeding, surgical duration, time to extubation and/or length of stay in the recovery room compared to inhaled anesthesia with sevoflurane or desflurane.
https://ift.tt/2lSGB5p
Very early introduction of semisolid foods in preterm infants does not increase food allergies or atopic dermatitis
The optimal age for the introduction of solid foods for infants has long been a controversial issue.
https://ift.tt/2NqbhaU
Seasonal and Regional Variation of Asthma-related Hospitalizations and Mortality among adults in the United States
Asthma morbidity and mortality is known to exhibit seasonal trends and periodicity. Prior studies done in the US and other countries have suggested seasonal variations in asthma hospitalization but report conflicting results. While most studies note a peak in winter,1–3 various trends have been noted in different age categories and regions.1–5
https://ift.tt/2z6LUro
Trends in the diagnosis and management of anaphylaxis in a tertiary care pediatric emergency department
Underdiagnosis of anaphylaxis is a major concern in the pediatric emergency department (PED), leading to failure to administer and prescribe intramuscular epinephrine treatment.
https://ift.tt/2Nqbefe
The Effects of Caregiver Depression on Childhood Asthma: Pathways and Mechanisms
This paper reviews the literature regarding the effects of caregiver depression on childhood asthma, and integrates the findings into a multilevel model of pathways by which these effects occur. The purpose is to further the understanding of the complex biopsychosocial nature of childhood asthma, and the key role that is played by caregiver depression.
https://ift.tt/2u1nqtK
Mold exposure affects the development of atopic dermatitis in infants with skin barrier dysfunction
Mold exposure is considered a risk factor for allergic diseases such as AD, although with some debate.1 The inconsistency of the results obtained in regard to this association may be due in part to differences in the dosage, time, and duration of the exposure. Skin barrier dysfunction and immune dysregulation have recently been highlighted as key factors in the development of AD. The transepidermal water loss (TEWL) level reflects skin barrier integrity, the loss of which is one of the most important features of AD.
https://ift.tt/2tVNcAB
A critically ill patient after a colchicine overdose below the lethal dose: a case report
Although 0.8 mg/kg is considered a lethal dose of colchicine, fatal cases of patients who followed a critical disease course after an intake below this lethal dose have been reported.
https://ift.tt/2ISVoGg
How can the risk of ovarian retorsion be reduced?
In the current treatment of idiopathic ovarian torsion, the use of oophorectomy has declined in favor of preserving the ovary. This approach brings with it the question of how to reduce the possibility of reto...
https://ift.tt/2KyDHBF
Drug Utilization Patterns and Adherence in Patients on Systemic Medications for the Treatment of Psoriasis: A Retrospective Comparative Cohort Study
There is limited data on adherence to systemic medications for psoriasis in real-world practice. Using a large US health insurance claims database, we found significantly increased odds of adherence to biologics compared to methotrexate. Dermatologists should consider adherence when choosing systemic treatments for psoriasis patients.
https://ift.tt/2tVGTNr
Calcium and zinc tune autoinflammatory toll-like receptor 4 signaling by S100A12
Publication date: Available online 3 July 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Christoph Kessel, Sabrina Fuehner, Jana Zell, Bastian Zimmermann, Stephan Drewianka, Sonja Brockmeyer, Dirk Holzinger, Claas Hinze, Helmut Wittkowski, Dirk Foell
Teaser
S100A12 is highly overexpressed in certain autoinflammatory diseases. Here we describe, that upon cellular release Ca2+ and Zn2+ can operate as molecular switch rendering S100A12 into a toll-like receptor 4-ligand to trigger sterile inflammation.https://ift.tt/2lS0R7b
Impact of bitter taste receptor phenotype upon clinical presentation in chronic rhinosinusitis
International Forum of Allergy &Rhinology, EarlyView.
https://ift.tt/2MMwOJz
A Sickening Tale
In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information by sharing relevant background and reasoning with the reader (regular type). The authors' commentary follows. A 44-year-old man presented to the…
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Oral Cancer Treatment: Still an Indication for Elective Neck Dissection?
ORL 2018;80:96–102
https://ift.tt/2KwQB3e
Solitary fibrous tumor of the liver. Report of three cases of a very rare tumor
Abstract
Introduction
Solitary fibrous tumors (SFT) can originate in any site of the body. Hepatic location is extremely rare. Presentation
We present three cases corresponding to women of 26, 40 and 78 years old, with the diagnose of a liver tumor, compatible with SFT, discovered on abdominal CT, who were submitted to right, left and atypical hepatectomy, respectively. The first patient has undergone multiple interventions for excision of metastatic lesions, and is stable with trabectedin; the second patient is asymptomatic with no evidence of recurrence; the third patient had recurrence of the disease after 16 months and passed away 32 months after diagnosis. Conclusion
Hepatic malignant SFT is very rare, although should be consider in the differential diagnosis of a single large hepatic tumor. Definitive diagnosis is based on histopathological and immunohistochemical findings; surgery remains the mainstay of treatment and careful follow-up is advised.https://ift.tt/2z6VCKA
Bilateral auditory ossicular expansions in a child with beta-thalassemia major: Case report and literature review
Publication date: September 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 112
Author(s): Melisha Sirisena, Catherine S. Birman, Amy J. McKibbin, Katie J. O'Brien
Marrow proliferation of the ossicular chain is a rare phenomenon. To date, only two other cases have described this rarity. We report a third paediatric case from Australia. A seven-year-old with thalassemia major demonstrated conductive impairment during surveillance for Deferasirox ototoxicity. Otitis media was assumed, however, CT scan of the petrous temporal bone revealed extramedullary haematopoiesis causing bilateral ossicular expansions and fixed conductive deficit. Reports of hearing loss in the thalassemia population focus on sensorineural impairment from iron chelation therapies. Clinicians should suspect ossicular deformation where treatment has been delayed, poorly controlled or conductive deficit persists without effusion.
https://ift.tt/2lRykPh
Malignant Transformation of a Desmoplastic Ameloblastoma to Squamous Cell Carcinoma: A Case Report
Abstract
Ameloblastomas are the most common odontogenic tumors, excluding odontomas. Several morphologic variants have been described including follicular, plexiform, acanthomatous, granular cell, basaloid and desmoplastic. Desmoplastic ameloblastoma differs from other conventional ameloblastomas microscopically, clinically, and radiographically. Ameloblastic carcinoma, the malignant counterpart of ameloblastoma is characterized by cytologic features of malignancy combined within the overall histologic features of conventional ameloblastoma. Malignant transformation of ameloblastoma to squamous cell carcinoma is a controversial subject. Here we report a case of a desmoplastic ameloblastoma with malignant transformation to squamous cell carcinoma in a 49 year old African American man. The patient underwent tumor resection and radiation therapy with no evidence of disease recurrence or progression 16 months post operatively. To our knowledge malignant transformation of a desmoplastic ameloblastoma to squamous cell carcinoma has not so far been reported. This observation may lend some support to the argument that desmoplastic ameloblastoma is phenotypically and biologically distinct entity.
https://ift.tt/2KsP2Dc
Primary carcinoma ex-pleomorphic adenoma of anterior commissure of the larynx
Source:Oral Oncology
Author(s): Josef Kovarik, Debra Milne, Max Robinson, Frank Stafford, Muhammad Shahid Iqbal
https://ift.tt/2z9LoJe
Prospective evaluation of patient reported swallow function with the Functional Assessment of Cancer Therapy (FACT), MD Anderson Dysphagia Inventory (MDADI) and the Sydney Swallow Questionnaire (SSQ) in head and neck cancer patients
Publication date: September 2018
Source:Oral Oncology, Volume 84
Author(s): Luke C. Peng, Xuan Hui, Zhi Cheng, Michael R. Bowers, Joseph Moore, Emilie Cecil, Amanda Choflet, Alex Thompson, Mariah Muse, Ana P. Kiess, Brandi R. Page, Christine G. Gourin, Carole Fakhry, Michal Szczesniak, Julia Maclean, Peter Wu, Ian Cook, Todd R. McNutt, Harry Quon
ObjectivesThe Functional Assessment of Cancer Therapy (FACT) instrument is comprised of a group of related and overlapping quality of life (QoL) questionnaires including a core general form, head and neck cancer (HNC)-specific items, and an expert-selected index (FACT-HNSI). Understanding how these relate to more HNC-specific instruments such as the MD Anderson Dysphagia Inventory (MDADI) and Sydney Swallow Questionnaire (SSQ) is vital for guiding their use in clinical trials.Materials and methodsHNC patients concurrently completed MDADI, SSQ, and FACT questionnaires at radiation oncology clinic visits (2015–2016). Spearman correlation coefficients were calculated between each FACT instrument and MDADI or SSQ. Unsupervised k-means cluster analyses were performed to identify clusters of similar QoL responses. Principal component analysis (PCA) identified the degree of variability explained by each instrument.ResultsWe identified 631 instances (363 patients) where the questionnaires were completed concurrently. Correlations between the various FACT measures and SSQ or MDADI were all significant (p < 0.001), but FACT HNC-specific subscale and FACT-HNSI showed the strongest correlation with MDADI and SSQ. Clustering identified 3 distinct groups of responses when combining instruments either pairwise or three-way. PCA revealed that MDADI and FACT HNC-specific subscale provide similar and likely redundant information.ConclusionFACT HNC-subscale and FACT-HNSI may be preferable over other FACT measures for use in clinical trials where patient-reported swallow function is evaluated. MDADI and FACT provide similar insights into HNC patient QoL while SSQ provides additional, complementary information which could serve to better stratify patients into groups with high, medium, and low QoL outcomes.
Graphical abstract
https://ift.tt/2tVsZe9
Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer
Abstract
Polymorphonuclear-MDSC (PMN-MDSC) have emerged as an independent prognostic factor for survival in NSCLC. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone. We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3+, CD3+CD4+ and CD3+CD8+), neutrophils (CD66b+) and polymorphonuclear-MDSC (PMN-MDSC; CD66b+CD11b+CD15+CD14-) as well as the concentration of 14 plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy donors (HD). In contrast to HD, NSCLC patients had a higher percentage of PMN-MDSC and neutrophils (P < 0.0001) but a lower percentage of CD3+, CD3+CD4+ and CD3+CD8+ cells. PMN-MDSC% negatively correlated with the levels of IL1-β, IL-2, IL-27 and IL-29. Two groups of patients were identified according to the percentage of circulating PMN-MDSC. Patients with low PMN-MDSC (≤ 8%) had a better OS (22.1 months [95% CI 4.3–739.7]) than patients with high PMN-MDSC (9.3 months [95% CI 0–18.8]). OS was significantly different among groups of patients stratified by both PMN-MDSC% and cytokine levels. In sum, our findings provide evidence suggesting that PMN-MDSC% in conjunction with the levels IL-1β, IL-27, and IL-29 could be a useful strategy to identify groups of patients with potentially unfavorable prognoses.
https://ift.tt/2KEKoS3
Headaches in Patients with Pituitary Tumors: a Clinical Conundrum
Abstract
Purpose of Review
Pituitary tumors account for approximately 17% of all intracranial neoplasms, with the majority being pituitary adenomas. Often, these are found incidentally during a workup for headache; however, the relationship between symptom and pathology remains unclear. The purpose of this article is to review the most recent literature on the epidemiology, pathophysiology, and management of headaches in patients with pituitary tumors.
Recent Findings
The current literature is limited, with few prospective trials focusing on this question. With the exception of pituitary apoplexy, the relationship between headaches and pituitary masses remains unclear. Intervention does not always improve headache and can lead to development of new headache syndromes.
Summary
Further research is needed to better elucidate the relationship between pituitary tumors and headaches. Headache alone is rarely an indication for surgical management of a pituitary adenoma.
https://ift.tt/2u3p51Z
Pharmacological Evaluation of Selected Medicinal Plants Used in the Management of Oral and Skin Infections in Ebem-Ohafia District, Abia State, Nigeria
Oral and skin infections contribute significantly to the global health challenges responsible for the current trend of increased morbidity and premature death. The purpose of this study was to document medicinal plants used in the management of oral and skin infections in Ebem-Ohafia Local Government Area (LGA), Abia State, and to characterize the in vitro antioxidant and antibacterial activity. The thin layer chromatography (TLC) profiling of ten of the selected folklore medicine was carried out using a various solvent system of different polarity index. The antioxidant capacity of the plant extracts was evaluated using chemical-based methods, and its antibacterial effect was investigated using disc diffusion and microdilution methods. Sixty-one plant species belonging to 26 families were discovered, and the most frequently cited species are Euphorbiaceae (18.03%), Fabaceae (11.47%), and Asteraceae (11.47%). All the plant extracts showed a promising free radical scavenging activity and efficient ferric reducing antioxidant power in a concentration-dependent manner possibly due to their richness in polyphenol with TLC profiling showing maximum three bands of phytochemicals. Also, the plant extracts exhibited a mild to weak antibacterial activity against our panel of bacterial strains having MIC values ranging from 256 to > 512 μg/ mL reflected in their zone of inhibition at 10 μg/disc. The data obtained for Breynia nivosa (BN), Eleusine indica (EI), Cassia alata (CA), Chromolaena odorata (CO), and Acalypha hispida (AH) extracts substantiate the traditional use of these herbal remedies in the region and open the possibility for the development of cheaper and affordable drugs in the treatment of oral and skin infections. Further studies are needed to identify active ingredient with strong antibacterial and antioxidant capacities along with their molecular mechanisms.
https://ift.tt/2lU1BsM
Management of chronic spontaneous urticaria: a worldwide perspective
The approaches to the diagnosis and treatment of chronic spontaneous urticaria (CSU) differ in various parts of the world. We sought to determine the adherence to international and national urticaria guideline...
https://ift.tt/2u5sFJ1
Intraoperative Tracheal Obstruction Management among Patients with Anterior Mediastinal Masses
Background. Patients suffering from undiagnosed obstruction of the central airways: the trachea and main stem bronchi are at increased risk for perioperative and postoperative complications, especially if general anesthesia is performed. Case Description. This report discusses a 30-year-old asymptomatic Caucasian female who faced recurrent distal airway collapse during mediastinoscopy for biopsy of an anterior mediastinal mass, which led to the inability to extubate her. This case examines the necessity of a thorough preoperative assessment especially in patients with undiagnosed tracheal obstruction and a precise coordination between anesthesiologist and surgeon in being able to perform a safe and smooth anesthesia, in order to avoid life-threatening complications and to reduce further morbidity. Methods. The scope of this case report is restricted to publications in all surgical and anesthesiological specialties among adult patient population. Main search key words were as follows: "tracheal obstruction," "general anesthesia," "mediastinum," and "tumors" Results. The literature supports an increased perioperative risk of airway obstruction with the use of general anesthesia in patients with anterior mediastinal masses. This case report suggests a perioperative anesthetic management modality for patients presenting with anterior mediastinal masses and who are at high risk of cardiovascular compression and tracheal obstruction. Thus, it is highly important to note that evidence-based recommendations are not available in the literature. Conclusions. This case report suggests perioperative management modalities performed by anesthesiologists in order to minimize the risk of airway obstruction among patients having anterior mediastinal masses and shed the lights on the importance of proper anesthetic and surgical planning in order to prevent intraoperative complications and improve the quality of healthcare provided to patients presenting critical cases.
https://ift.tt/2MKT3jg
Acute Pain Is Associated With Chronic Opioid Use After Total Knee Arthroplasty
Background and Objectives Pain scores are routinely reported in clinical practice, and we wanted to examine whether this routinely measured, patient-reported variable provides prognostic information, especially with regard to chronic opioid use, after taking preoperative and perioperative variables into account in a preoperative opioid user population. Methods In 32,874 preoperative opioid users undergoing primary total knee arthroplasty at Veterans Affairs hospitals between 2010 and 2015, we compared preoperative and perioperative characteristics in patients reporting lower versus higher acute pain (scores ≤4/10 vs >4/10 averaged over days 1–3). We calculated the propensity for lower acute pain based on all available data. After 1:1 propensity score matching, to identify similar patients differing only in acute pain, we contrasted rates of chronic significant opioid use (mean >30 mg/d in morphine equivalents) beyond postoperative month 3, discharge prescriptions, and changes in postoperative versus preoperative dose categories. Sensitivity analysis examined associations with dose escalation. Results Rates of chronic significant opioid use (21% overall) differed in patients with lower versus higher acute pain (36% vs 64% of the overall cohort). After propensity matching (total n = 20,926 patients) and adjusting for all significant factors, lower acute pain was associated with less chronic significant opioid use (rates 12% vs 16%), smaller discharge prescriptions (ie, supply
https://ift.tt/2Kstvux
https://ift.tt/2Kstvux
Functional maturation and in vitro differentiation of neonatal porcine islet grafts
Background There is a strong rationale to pursue the use of neonatal porcine islets (NPIs) as an unlimited source of islets for clinical xenotransplantation. Since NPIs are composed of immature insulin producing beta (ß) cells and ductal precursor cells, they provide an ideal model to examine culture conditions to enhance ß cell proliferation and/or ß cell neo-formation from ductal cells. In an attempt to optimize the potential of NPIs as a source of ß cell grafts, we utilized an in vitro differentiation protocol and measured its effect on the functional maturation and differentiation of NPIs. Methods Pancreata from 1 to 3-day old neonatal pigs were digested and cultured in standard Ham's-F10 media for 5 days. Each independent preparation was then further cultured in DMEM-F12 differentiation media containing growth factors added in a stepwise fashion, or cultured in control Ham's-F10 media. After 20 days in culture, islets were assessed for insulin secretory capacity, cellular composition, gene expression and metabolic activity after transplantation in immunedeficient diabetic mice. Results Compared to control islets, differentiated islets exhibited a significantly higher proportion of endocrine cells, proliferating cell nuclear antigen double positive ß cells, and an enhanced glucose stimulated insulin secretory activity. Mice transplanted with differentiated islets had significantly lower blood glucose values at weeks 18 and 20 compared to nondifferentiated controls and were shown to be more glucose tolerant. Conclusions Culturing NPIs in a 20-day step-wise differentiation media increases the proportion of endocrine cells and augments both in vitro and in vivo function of the islets. Received 13 February 2018. Revision received 13 June 2018. Accepted 26 June 2018. * Contributed equally Corresponding Author Dr. Gregory S. Korbutt, Alberta Diabetes Institute, 5-002 Li Ka Shing Center, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1. T: (780) 492-4657 F: (780) 492-5501. Email: korbutt@ualberta.ca Authorship TH and LKS performed experiments, presented and analyzed the data and contributed to writing the manuscript. BS conducted all transplants and glucose tolerance tests. GSK designed the study, financial support, data interpretation, manuscript review and final editing of manuscript. Disclosure The authors declare no conflicts of interest associated with this manuscript. Funding This study is supported by the Canadian Institutes of Health Research (Grant #MOP 119500). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2KF84FJ
https://ift.tt/2KF84FJ
How we approach combination antifungal therapy for invasive aspergillosis and mucormycosis in transplant recipients
Invasive aspergillosis and mucormycosis are life-threatening complications in solid organ and hematopoietic cell transplant recipients. Despite medical advancements in the care of these patients and the availability of new mold-active drugs over the past decade, the outcomes remain suboptimal. Therefore, there has been increased interest in the use of combination antifungal therapy, in hopes that leveraging the possible in vitro synergy of these agents will improve the prognosis of invasive mold disease. However, there has been a large disconnect between the results of experimental and clinical investigations, as clinical studies have not unequivocally demonstrated the superiority of combination therapy over monotherapy. This is particularly true for mucormycosis, where the rarity of the condition has made it nearly impossible to prospectively study novel therapeutic strategies. We review the current standard of antifungal therapy and the preclinical and clinical data addressing the merit of combination therapy, and we provide guidance to optimize the management of these mycoses. Received 4 June 2018. Revision received 22 June 2018. Accepted 26 June 2018. *Address correspondence to: Nina Singh M.D., Infectious Diseases Section, Veterans Affairs Medical Center, University Drive C, Pittsburgh, PA 15240. Tel: +412-360-1688; E-mail: nis5@pitt.edu. AUTHORSHIP GH wrote the first draft of the article. NS made revisions to the article and approved the final draft. The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2KLLmsq
https://ift.tt/2KLLmsq
YB-1 increases glomerular, but decreases interstitial fibrosis in CNI-induced nephropathy
Publication date: Available online 3 July 2018
Source:Clinical Immunology
Author(s): Lydia Gibbert, Daniela Hermert, Jialin Wang, Daniel Breitkopf, Christina Alidousty, Matthias Neusser, Clemens D. Cohen, Elisabeth Gröne, Iris Macheleidt, Thomas Rauen, Gerald S. Braun, Jürgen Floege, Tammo Ostendorf, Ute Raffetseder
Calcineurin inhibitors (CNIs) are a cornerstone of the current treatment in solid organ transplantation and autoimmune disease. However, CNIs also bear deleterious effects as they cause glomerular and tubulointerstitial fibrosis in the kidney. We recently identified Y-box protein-1 (YB-1) as a novel downstream effector of CNI-signaling in the cytoplasm of glomerular cells. In the present study, we corroborate the pro-fibrotic role of YB-1 in glomeruli of patients under CNI-treatment. Such effects in glomeruli are significantly mitigated in CNI-treated mice with half-normal YB-1 expression (Yb1+/−). Surprisingly, in the tubulointerstitium we observe an opposite role of the CNI-YB-1 axis. Here, YB-1 is predominantly located to the nuclei and represses transcription of several extracellular matrix genes. Consistently, CNI-treatment in Yb1+/ mice markedly increases pro-fibrotic changes in the tubulointerstitium. In summary, our data provide evidence that fibrotic CNI-induced YB-1 effects in glomerular cells need to be contrasted with beneficial anti-fibrotic effects in the tubulointerstitium.
Graphical abstract
https://ift.tt/2zaIYdf
APECED in Turkey: A case report and insights on genetic and phenotypic variability
Source:Clinical Immunology
Author(s): Alessandra Fierabracci, Marsha Pellegrino, Federica Frasca, Sara Sebnem Kilic, Corrado Betterle
APECED is a rare monogenic recessive disorder caused by mutations in the AIRE gene. In this manuscript, we report a male Turkish patient with APECED syndrome who presented with chronic mucocutaneous candidiasis associated with other autoimmune manifestations developed over the years. The presence of the homozygous R257X mutation of the AIRE gene confirmed the diagnosis of APECED syndrome. We further performed literature review in 23 published Turkish APECED patients and noted that Finnish major mutation R257X is common in Turks. In particular, we assessed retrospectively how often the Ferre/Lionakis criteria would have resulted in earlier diagnosis in Finns, Sardinians and Turks in respect to the classic criteria. Since an earlier diagnosis could have been possible in 18.8% of Turkish, in 23.8% of Sardinian and 38.55% of Finnish patients we reviewed from literature, Ferre/Lionakis criteria could indeed allow in future earlier initiation of immunomodulatory treatments, if found effective in future studies.
https://ift.tt/2lPY7ax
Avocado-Induced Food Protein-Induced Enterocolitis Syndrome (FPIES): Case Series of an Emerging Trigger,
Publication date: Available online 4 July 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Sheeba Cherian, Kathryn Neupert, Pooja Varshney
https://ift.tt/2u7YH7s
Macrophagic myofasciitis: a challenging diagnosis
A 25-year-old man admitted for generalised muscle pain with an insidious onset 3 years ago. He had exercise intolerance and decrease in muscle strength, requiring gait support. He was previously healthy, with no chronic medication or recent history of drugs or toxics. National vaccination plan actualised with hepatitis B and tetanus vaccines administered 10 and 2 years, respectively, before symptom onset. No analytical, imaging or electromyography changes were found. Muscle biopsy revealed an inflammatory infiltrate predominantly macrophagic with aluminium deposits suggestive of macrophagic myofasciitis (MMF). It is probably associated with vaccines previously administered. MMF lesion can be regarded as pathological only if detected at least 18 months after last aluminic immunisation, as our case illustrates.
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Rare glomangiosarcoma of the tongue
The glomus tumour is a rare neoplasm derived from the glomus apparatus. Subungual sites are most common with only three published cases involving the dorsal tongue. To our knowledge, this is the first case of an intraoral malignant glomus tumour (glomangiosarcoma) to be published in English literature. We report a case of a single glomus tumour located on the posterior dorsal tongue of a middle-aged man, which was surgically excised. Immunohistological features were indicative of a glomus tumour; however, in this case, malignant features were also discovered, warranting re-excision.
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Apert syndrome: Be aware of the 'dodgy hip!
Apert syndrome is a rare congenital disorder characterised by craniosynostosis, midface hypoplasia and syndactyly of hands and feet. Here we present a case of a 44-year-old woman, with a genetic diagnosis of Apert syndrome from birth, who presented with symptomatic left-sided hip osteoarthritis secondary to femoral abnormalities. She proceeded to have a total hip replacement. This case report describes the rare occurrence to identify a possible association between Apert syndrome and hip abnormalities.
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Clinical spectrum of Dyke-Davidoff-Masson syndrome in the adult: an atypical presentation and review of literature
Dyke-Davidoff-Masson Syndrome (DDMS) is a rare condition usually diagnosed in paediatric patients with clinical features of hemiparesis, seizures, mental retardation and contralateral cerebral hemiatrophy on neuroimaging. This report follows the case of a 22-year-old man presenting with seizures and hemiatrophy and hemiparesis. On review of cases the most common neuroimaging findings were cerebral hemiatrophy (100%) followed by hemicalvarial thickening (71.4%) and hyperpneumatisation of sinuses (71.4%). Apart from our patient, all nine cases with data on epilepsy control had drug-resistant epilepsy. The onset of seizures in adulthood, block vertebra, short stature, absence of mental retardation and well-controlled epilepsy on monotherapy makes our case exceptional—even bringing to mind the possibility of a DDMS variant. This report exhaustively reviews the wide range of clinical and radiological manifestations of DDMS in the adult, thereby adding to the literature on an unusual syndrome that causes significant neurological morbidity.
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Oropharyngeal paraganglioma presenting with stridor: an unusual presentation
Head and neck paraganglioma is a rare disease to encounter in clinical practice and involvement of the base of the tongue in the oropharynx is yet to be described in the current literature. Although various surgical approaches have been described in the literature, transcervical mandibular swing is an effective technique for adequate exposure and complete excision of the oropharyngeal paraganglioma with adequate control on bleeding especially when it is assisted by coblation.
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A garlic burn
Description
A 45-year-old woman presented with a 12 hour history of painful blisters and erythema over the dorsum of her left great toe. The patient reported applying freshly sliced raw garlic to the dorsum of her left great toe during the past 4 weeks for up to 4 hours a day to treat a fungal nail infection.
On examination, the left great toe was swollen, erythematous and blistering. Her great toenail was yellow and slightly lifted from the nail bed. Clinically, she had a partial thickness burn and onychomycosis (figure 1). The skin on the toe was pH 9. The toe was irrigated with water until a normal pH was reached, and the blisters de-roofed.
Figure 1
Clinical appearance of garlic burn in this patient. The image shows blistering and erythema consistent with a partial thickness burn. The toenail is discoloured due to the underlying fungal...
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