Head and Neck Medicine by Alexandros G.Sfakianakis: 01/10/18

Τετάρτη 10 Ιανουαρίου 2018

Endometrial Adenocarcinoma With Pulmonary Recurrence

Description

We present the case of an 83-year-old woman with a history of grade 1 stage IB endometrial cancer (endometrial adenocarcinoma) (figure 1) involving the lower uterine segment. She underwent robotic hysterectomy with right salpingo-oophorectomy followed by brachytherapy. A year and a half later, she presented with difficulty in breathing. A chest X-ray showed 8 mm nodular density in the right lower lobe. The above finding was confirmed with CT. Given the concern for a malignant lesion, positron emission tomography/CT scan was performed, which revealed two metabolically active lung nodules, measuring 1.2 cm in the right middle lobe and other in the right lower lobe measuring 1.2 cm (figure 2). Video-assisted thoracoscopic wedge resection of the right lower lobe lung nodule was performed. The frozen section and histopathology revealed papillary adenocarcinoma (figures 3 and 4); nuclear staining was positive for oestrogen receptors and negative for thyroid...

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Cervical ganglioneuroma: clinical and radiological features of a rare tumour

Description

Ganglioneuromas are rare benign tumours of neurogenic origin that most frequently develop in the cervical sympathetic chain,1 2 with genetic associations demonstrated with Neurofibromatosis type 1 (NF-1). We report the case of a 41-year-old woman with a history of cavum neoplasm at the age of 23. This tumour was classified after assessment of extension as T1N0M0 (tumour, node, metastases). Pathological examination of a biopsy concluded to a keratinising squamous cell carcinoma. The patient was then irradiated (2D Cobalt radiotherapy). The patient presented with gait trouble that appeared a few weeks ago. Clinical examination found a Brown-Séquard syndrome with paresis and loss of proprioception on the left side, and loss of pain and temperature sensation on the right side. Medullar MRI (figures 1 and 2) showed an intradural extramedullary well-circumscribed mass with an hourglass shape from C5 to C6 extending through the...

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Rare cause of pulmonary cavitation in a 75-year-old man

A 75-year-old man of Asian descent presented to the acute medical unit with signs and symptoms suggestive of a community-acquired pneumonia. He had multiple comorbidities and was relatively immunocompromised as a result. Initial investigations supported the diagnosis of community-acquired pneumonia complicated by a cavitating lung lesion, and the patient was treated as per hospital guidelines. He continued to deteriorate despite appropriate therapy and developed a hydropneumothorax, requiring the insertion of a chest drain. A diagnosis of pulmonary mucormycosis (Rhizopus microsporus) was made based on microbiology results from pleural aspirate, and patient was treated with intravenous antifungals. The patient was referred to the thoracic team for consideration of surgical intervention but was not suitable due to his multiple comorbidities. This case highlighted the importance of early consideration of fungal infection in patients with multiple risk factors and the need for aggressive therapy to ensure the best outcome.

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Intradiploic cephalocele: a rare entity at a rare site

Description

A 52-year-old woman presented with complaints of non-specific headache. The patient had a history of head injury 1 year ago. Clinical neurological examination was nil significant. The skin over the occipital region is normal. No prior investigations were done immediately after the injury. MRI of the brain at present showed small intradiploic cerebrospinal fluid (CSF)-filled defect with herniation of foliae of the right cerebellar hemisphere (figure 1). The rest of the brain parenchyma revealed no abnormality and no skull fracture was seen. Features were suggestive of intradiploic cephalocele involving cerebellar foliae.

Figure 1

Axial Fluid attenuated inversion recovery (A), T2 (B), coronal T2 (C) and sagittal T1 (D) images at the level of the cerebellum showing small calvarial defect in the occipital bone on the right side with intradiploic herniation of the right cerebellar foliae (black arrows).

A cephalocele is...

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Sternocleidomastoid tumour in neonate: fibromatosis colli

Description

We report a case of a 4-week-old female neonate who was admitted to the hospital for a anterior right lump of the neck, perceived by his mother the day before. The mother also noticed a preferential tilting of the head towards right. He was an otherwise full-term healthy baby, with a history of instrumented delivery. There was no fever, trauma or respiratory symptoms/signs. Family history was irrelevant. On examination, the neck swelling was a small firm, partially mobile, no warm on touch and apparently painless mass, with approximately 1.5–2 cm soft tissue mass, attached to the right sternocleidomastoid muscle. There was no restriction of neck movements. Ultrasonography (USG) revealed a 13 mm fusiform thickening of the right sternocleidomastoid muscle, with maintained structure of muscle fibres (figures 1 and 2). No cervical lymphadenopathy, signs of infiltration or other anomalies were found (figures 1 and...

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Ninety-year-old man with hypereosinophilia, lymphadenopathies and pruritus

We report a case of a 90-year-old man with hypereosinophilia, lymphadenopathies and skin lesions, namely lichenification and pruritus. An aetiological investigation was performed, and a bone marrow (BM) biopsy and aspirate showed a hypercellular marrow with hypereosinophilia without dysmorphia or abnormal elements, and the BM and inguinal node's immunophenotyping denied any presence of abnormal lymphoid cell population. The inguinal node biopsy revealed a multinodular proliferation of large cells S100 and CD1a⁺, and a diagnosis of Langerhans cell histiocytosis was made. The hypereosinophilia and skin lesions were managed with corticotherapy with substantial improvement of cutaneous lesions and lymphadenopathies and normalisation of eosinophil count. Finally, to define if it is a single or multisystem disease, a skin biopsy will be necessary.

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Head circumference - a useful single parameter for skull volume development in cranial growth analysis?

Response to ‘Serological diagnostics in the detection of IgG autoantibodies against human collagen VII in epidermolysis bullosa acquisita: a multicentre analysis': reply from authors

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Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China

Abstract

Background

The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China, and to study the impact of the intensity and time of pollen exposure on PiAR prevalence.

Methods

A multistage, clustered and proportionately stratified random sampling with a field-interviewer administrated survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.

Results

A total of 6043 subjects completed the study; with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P=0.024) but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P<0.001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types; which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature and precipitation (P<0.05), but negatively with wind speed and pressure P<0.05).

Conclusion

PiAR prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.

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Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B-cell response in seasonal allergic rhinitis patients

Abstract

Background

Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol.

Methods

In a prospective, dose-escalation study, 61 grass pollen–allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4, and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8).

Results

No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became non-reactive to CPT. sIgG4 levels were higher at V6 (8.1-fold, P<0.001) and V8 (12.2-fold, P<0.001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (–54.6%, P<0.001) and V8 (–71.6%, P<0.001) compared to V1. The absolute decrease in IgE-facilitated allergen binding was 18% (P<0.001) at V6 and 25% (P<0.001) at V8.

Conclusion

Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.

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Relationship between α-melanocyte stimulating hormone levels and therapeutic outcome of melanocyte transplantation and phototherapy in non-segmental patients with vitiligo: A prospective study

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„Lernen im geschützten Umfeld“: Implementierung in die Fort- und Weiterbildung

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 35-46
DOI: 10.1055/s-0043-105259

Aktuelle Aus- und Fortbildungskonzepte in der Akut- oder Notfallmedizin beinhalten Simulations- und Skill-Trainings unter Berücksichtigung von Methoden und Mechanismen der Fehler- und Zwischenfallprävention wie Human Factors, Shared mental Models und Closed-Loop-Communication. Immer noch ungeklärt ist die Frage nach der optimalen Kombination der einzelnen Methoden und Inhalte eines Fortbildungsprogramms in Abhängigkeit von individuellen Abteilungen eines Krankenhauses und dem einzelnen Mitarbeiter bzw. seinem individuellen Ausbildungsstand. Ein von uns angebotenes Konzept ist das „Lernen im geschützten Umfeld": Hier werden Teilnehmer und Patient vor den negativen Auswirkungen einer konventionellen klinisch-praktischen Ausbildungssituation beschützt. Gleichzeitig profitieren die Teilnehmer in unserem Fortbildungsprogramm von standardisierten Kursmodellen. Das Ziel der optimalen Vorbereitung auf die klinische Tätigkeit und einer möglichst praktischen bzw. wirklichkeitsnahen Aus- und Fortbildung wird durch eine ständige Re-Evaluation der Inhalte und Methoden komplettiert. Die Implementierung eines solchen multimodalen Teamtrainings ist für jede Institution individuell anzupassen. Die Methoden zur Implementierung sollten standardisiert angewendet werden. Wir empfehlen eine Curriculumsentwicklung auf Grundlage des „Kern-Zyklus". Auf dieser Basis gelingt die Kombination aus „Lernen im geschützten Umfeld" und Zwischenfalltraining zur optimalen Vorbereitung auf eine akutmedizinische, klinische Tätigkeit mit dem Ziel einer höchstmöglichen Patientensicherheit.
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Georg Thieme Verlag KG Stuttgart · New York

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Kompetenzbasierte Ausbildung im „geschützten Umfeld“: vom Schonraum zum Realraum

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 12-19
DOI: 10.1055/s-0043-105257

„Lernen im geschützten Umfeld" ist ein häufig gebrauchter, aber unklarer Begriff im Rahmen der anästhesiologischen postgradualen Weiterbildung. Dieser Artikel beleuchtet seine Bedeutung in der Anästhesiologie – einschließlich Lehr- und Lernstrategien, wie kompetenzorientierte und simulationsbasierte Ausbildung. Ein Versuch der Klassifikation von Simulatoren und Unterrichtsmethoden sowie deren Probleme bei der Umsetzung runden den Beitrag ab.
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Georg Thieme Verlag KG Stuttgart · New York

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Behandlung im Voraus planen – Bedeutung für die Intensiv- und Notfallmedizin

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 62-70
DOI: 10.1055/s-0042-118690

Behandlung im Voraus planen (BVP) – im Englischen Advance Care Planning (ACP) – etabliert sich auch in Deutschland als ein neues Konzept zur Realisierung wirksamer Patientenverfügungen. Das Konzept beinhaltet Prozesse zur Ermittlung, Dokumentation und Umsetzung von Behandlungswünschen für den Fall, dass die Betroffenen nicht (mehr) selbst entscheiden können.
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Georg Thieme Verlag KG Stuttgart · New York

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Begünstigt Kaudalanästhesie postoperative Komplikationen nach Hypospadie-OP?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 6-7
DOI: 10.1055/s-0043-123122

Georg Thieme Verlag KG Stuttgart · New York

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Hyperchlorämie ist mit akutem Nierenversagen nach SAB verbunden

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 7-8
DOI: 10.1055/s-0043-123121

Georg Thieme Verlag KG Stuttgart · New York

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Lernen im geschützten Umfeld

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 10-11
DOI: 10.1055/s-0043-122170

Georg Thieme Verlag KG Stuttgart · New York

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Etomidat-Analogon mit verringerter Nebennierensuppression

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 8-8
DOI: 10.1055/s-0043-117029

Georg Thieme Verlag KG Stuttgart · New York

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Simulation als Fortbildungsmethode zur Professionalisierung von Teams

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 20-33
DOI: 10.1055/s-0043-105261

Simulation ist eine Methode, virtuelle Lernumgebungen zu erzeugen. Mittels Simulation können Technical Skills, aber auch Soft Skills wie die Funktionsfähigkeit von Teams sehr gut vermittelt werden. Dieser Team-Aspekt wird nachfolgend vor dem Hintergrund spezifischer Trainingsmethoden näher beleuchtet. Der Artikel bezieht sich dabei auf „Zwischenfalltrainings", die in den Zentren der Autoren einen großen Anteil des Kursangebotes einnehmen.
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Georg Thieme Verlag KG Stuttgart · New York

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The Same Procedure As Last Year?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 9-9
DOI: 10.1055/s-0043-123165

Georg Thieme Verlag KG Stuttgart · New York

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„Das Kind hat einen Fremdkörper verschluckt“ – was tun?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 48-60
DOI: 10.1055/s-0042-120991

Sowohl Ingestions- als auch Aspirationsunfälle sind häufige Ereignisse bei Kindern. Sie können unmittelbar lebensbedrohlich sein oder bei fehlender direkter Bedrohung dennoch erhebliche langfristige Beeinträchtigungen für die Kinder verursachen. Der Beitrag zeigt die diagnostischen und therapeutischen Möglichkeiten und Notwendigkeiten auf, durch die eine bestmögliche Sicherheit und möglichst geringe Folgeschäden zu gewährleisten sind.
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Georg Thieme Verlag KG Stuttgart · New York

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Neurologischer Schaden nach Wirbelsäulen-OP

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 71-75
DOI: 10.1055/s-0043-122628

Schlichtungsstellen für Arzthaftpflichtfragen bieten Patienten, Ärzten und Versicherern eine Möglichkeit, Arzthaftungsstreitigkeiten außergerichtlich zu klären. In der Rubrik „Fälle der Schlichtungsstelle" stellen wir abgeschlossene Fälle aus der Schlichtungsstelle für Arzthaftpflichtfragen der norddeutschen Ärztekammern vor.
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Georg Thieme Verlag KG Stuttgart · New York

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Entwicklung neuer Antibiotika: Endpunkte klinischer Studien teils ungeeignet

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 5-6
DOI: 10.1055/s-0043-117062

Georg Thieme Verlag KG Stuttgart · New York

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Atemübungen schützen ältere Patienten vor gefährlichen Lungenentzündungen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 753-753
DOI: 10.1055/s-0043-121213

Georg Thieme Verlag KG Stuttgart · New York

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Interventionen zur präoperativen Unterstützung geriatrischer Patienten mit Frailty

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 777-783
DOI: 10.1055/s-0043-104684

Der stetig zu beobachtende demografische Wandel geht mit veränderten Anforderungen an die Patientenbetreuung einher. Ältere Patienten weisen häufig einen erhöhten Behandlungsbedarf und eine höhere Komplexität des klinischen Gesamtbildes auf. Dieser Umstand ist – abgesehen von der Routineversorgung – besonders dann zu beachten, wenn eine angedachte Intervention zu schweren und potenziell lebensbedrohlichen Komplikationen führen kann.
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Georg Thieme Verlag KG Stuttgart · New York

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Therapiebegrenzung: DIVI empfiehlt neuen Dokumentationsbogen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 752-753
DOI: 10.1055/s-0043-119947

Georg Thieme Verlag KG Stuttgart · New York

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Zervikale Plexusblockaden

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 806-813
DOI: 10.1055/s-0043-115204

Eine vollständige Blockade des Plexus cervicalis ist weder erwünscht noch ausreichend für eine chirurgische Anästhesie in der vorderen Halsregion. Supplementierungen durch Opioide oder topische Lokalanästhetika sind daher häufig. Die Blockade beteiligter Hirnnerven und des Truncus sympathicus verbessert möglicherweise die Anästhesiequalität, führt aber auch zu typischen Nebenwirkungen. Dieser Beitrag liefert anatomisches Hintergrundwissen und stellt Indikationen vor – auch außerhalb der Karotischirurgie.
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Georg Thieme Verlag KG Stuttgart · New York

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Warum und wie sollte ich Frailty erfassen? – ein Ansatz für die Anästhesieambulanz

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 765-776
DOI: 10.1055/s-0043-104682

Frailty (Gebrechlichkeit) ist eine Einschränkung der physiologischen Reserve bei älteren Patienten mit schwerwiegenden individuellen und sozioökonomischen Folgen. Multiple Aspekte der Patientenbehandlung sowie das Outcome werden durch Frailty nachhaltig beeinflusst. Obwohl mehr als 60 Messinstrumente existieren, sind die Erfassung und Berücksichtigung funktioneller Assessments in der klinischen Routine unzureichend umgesetzt. Das interdisziplinäre und interprofessionelle Verständnis, warum und wie Frailty beurteilt werden sollte, ist die Grundlage für die dauerhafte Implementierung. Der Artikel zeigt die Auswirkungen von Frailty und Vorteile einer Früherkennung auf und gibt einen Überblick über die wichtigsten Instrumente, die in der Frailty-Erkennung und -Bewertung verwendet werden können. Die frühe präoperative Detektion bietet ein vielfältiges Optimierungspotenzial für die peri- und intraoperative Versorgung. Verschiedene Frailty-Assessment-Tools körperlicher, kognitiver und psychosozialer Domänen werden vorgestellt und diskutiert. Frailty-Assessments variieren immens in Bezug auf die erforderliche Zeit, die Ausrüstung und das Fachwissen zur Durchführung. Wir empfehlen mindestens einen Test für die einzelnen Dimensionen von Frailty, um ein holistisches Bild der geriatrischen Patienten zu erhalten. Die Bewertung von Frailty sollte übergreifend in die interdisziplinären Strukturen der klinischen Routine implementiert werden, um die Patientensicherheit sowie das kurz- und langfristige Outcome zu verbessern.
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Georg Thieme Verlag KG Stuttgart · New York

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Vielen Dank!

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 754-754
DOI: 10.1055/s-0043-121256

Georg Thieme Verlag KG Stuttgart · New York

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Die meisten Todesbescheinigungen weisen Fehler auf

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 752-752
DOI: 10.1055/s-0043-121621

Georg Thieme Verlag KG Stuttgart · New York

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Patienten mit Frailty: Anästhesiologie in der Verantwortung

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 756-757
DOI: 10.1055/s-0043-117836

Georg Thieme Verlag KG Stuttgart · New York

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Laser treatment of primary axillary hyperhidrosis: a review of the literature

Abstract

Hyperhidrosis o`ccurs when the body produces sweat beyond what is essential to maintain thermal homeostasis. The condition tends to occur in areas marked by high-eccrine density such as the axillae, palms, and soles and less commonly in the craniofacial area. The current standard of care is topical aluminum chloride hexahydrate antiperspirant (10–20%), but other treatments such as anticholinergics, clonidine, propranolol, antiadrenergics, injections with attenuated botulinum toxin, microwave technology, and surgery have been therapeutically implicated as well. Yet, many of these treatments have limited efficacy, systemic side effects, and may be linked with significant surgical morbidity, creating need for the development of new and effective therapies for controlling excessive sweating. In this literature review, we examined the use of lasers, particularly the Neodynium:Yttrium-Aluminum-Garnet (Nd:YAG) and diode lasers, in treating hyperhidrosis. Due to its demonstrated effectiveness and limited side effect profile, our review suggests that Nd:YAG laser may be a promising treatment modality for hyperhidrosis. Nevertheless, additional large, randomized controlled trials are necessary to confirm the safety and efficacy of this treatment option.

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Narrow band imaging versus laryngovideostroboscopy in precancerous and malignant vocal fold lesions

Abstract

Background

This is a comparative analysis of the diagnostic accuracy of narrow band imaging (NBI) and laryngovideostroboscopy (LVS) in the assessment of premalignant and malignant vocal fold lesions.

Methods

A prospective analysis was performed on 105 consecutive patients with vocal fold lesions. The NBI and LVS were obtained before the microsurgery.

Results

The NBI and LVS showed no significant differences in identifying premalignant and malignant pathologies. However, in analysis restricted to identification of only malignant lesions, the specificity (88.9% vs 20.6%), accuracy (90.5% vs 51.4%), and positive predictive value (PPV; 84.8% vs 45.1%) were significantly higher for NBI (P value < .001; .015; and .045, respectively). A comparison of LVS scored results relative to each NBI type revealed statistically significant differences (P < .001). A moderate positive correlation between NBI and LVS was demonstrated (P = .54).

Conclusion

The NBI and LVS are useful, complementary tools in evaluating early potential vocal fold malignancies. The NBI was superior to LVS on several statistical analyses.

http://ift.tt/2D36uK7

Unilaterale Halsschwellung – eine überraschende Differentialdiagnose

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-123651

Georg Thieme Verlag KG Stuttgart · New York

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Kartagener’s syndrome: a case report

Kartagener's syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive inherited disorder characterized by the clinical triad of chronic sinusitis, bronchiectasis, and situs inversus. Abnormal...

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Cytotoxic and inflammatory effects of alendronate and zolendronate on human osteoblasts, gingival fibroblasts and osteosarcoma cells

The aim of this paper was to assess the effects of zoledronate (ZOL) andalendronate (FOS) on apoptotic behaviour and gene expression of pro- and inflammatory cytokines of three cell types (human osteoblasts, human gingival fibroblasts and human osteogenic sarcoma cell lines) during a period of 4 weeks.

http://ift.tt/2CZ7r73

Thirty-day readmissions following parathyroidectomy: Evidence from the National Readmissions Database, 2013–2014

Parathyroidectomy is one of the most common procedures performed in the United States, and are increasingly being performed safely in the outpatient setting. However, complications from surgery can be life-threatening, and thus an understanding of who may be at risk is essential. We analyzed and compared the risk factors for patients readmitted within 30 days following inpatient parathyroidectomy for primary or secondary hyperparathyroidism.

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‘Hidden’ occupational allergens such as additives

Purpose of review With the development of innovative technologies, new agents are continually introduced to the workplace. Some of these agents can act as hidden allergens whenever they are not declared in the product labels or whenever their health hazards are unknown. This review article focuses on the identification and description of unusual and/or hidden allergens recently incriminated in occupational diseases. Recent findings Occupational exposure is an important global health issue that can induce respiratory and cutaneous disorders, as well as life-threatening anaphylaxis. Apart from the classic forms of occupational exposure, reports have emerged from nonconventional or newly identified allergens or additives. These compounds are substances added to another in order to alter or improve the general quality or to counteract undesirable properties, and some of them may behave as potent and frequently hidden allergens. These highly uncommon and/or hidden allergens belong to several categories: foods, spices, cosmetics, insects, enzymes, chemicals, drugs, preservatives, and coloring agents, among others. Summary A high level of suspicion and awareness about the potential hidden allergens is necessary to ascertain the allergens implicated. It is of utmost importance to identify the specific eliciting agents of the occupational diseases in order to avoid strictly further exposure to them. Correspondence to Santiago Quirce, MD, PhD, Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ), 28046 Madrid, Spain. E-mail: squirce@gmail.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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High intraoperative inspiratory oxygen fraction and risk of major respiratory complications

British Journal of Anaesthesia, 2017; 119(1): 140–9, DOI 10.1093/bja/aex128

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EAACI Guidelines on Allergen Immunotherapy – Out With the Old and In With the New

Abstract

Occurring in both developed and developing countries and across all ethnic groups and ages allergic diseases represent a global health problem. During the last few decades, there has been an increase in the prevalence of allergic diseases and it has been predicted that by 2025 half of the entire EU population will be affected [1]. The three major management strategies are avoidance, symptom control by pharmacotherapy and allergen immunotherapy (AIT). By contrast with symptom control by pharmacotherapy AIT aims to modify the immune system via tolerance induction [2] and is potentially able to alter the course of allergic diseases [3]. The potential preventive effect of AIT is currently being explored for pollen [4].

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With tree nut sensitization, take the current when it serves, or lose our ventures

Abstract

Tree nut allergy affects approximately 1.4-2.3%, depending on the study methodology, patient age, and region in which the study was conducted.^1,2 Tree nut allergy can be severe, and tends to persist throughout life.^1,3 Tree nut is not a singular allergen like the other allergens—we use the term "tree nut" to refer to these items, but in essence it can refer to one nut, eight nuts, or per the US Food and Drug Agency classification, on the order of 19 items.^1,4 Older, more conservative practice is to treat one nut as "all nuts", and instruct avoidance of all tree nuts where there is a clinical allergy proven to just one. This is often supported by high rates of co-sensitization, which is high among tree nuts because of structural similarity, and fueled concerns of cross-contamination, proper identification, or labeling confusion.^1,5

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Cell therapy for severe hemophilia: study has come full circle

No abstract available

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Clinical and Pathological Features of Plasma Cell-Rich Acute Rejection after Kidney Transplantation

AbstractBackgroundPlasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection characterized by the presence of mature plasma cells. In general the prognosis of PCAR is poor, and its clinical and pathological features remain unclear.MethodsWe performed a retrospective observational study and compared allograft survival between kidney transplant recipients who developed PCAR and those who did not develop PCAR. We further analyzed clinical and pathological risk factors for allograft failure in PCAR patients.ResultsOf 1,956 recipients, 40 developed PCAR. There was a higher prevalence of deceased donor transplants (27.5% vs. 11.7%, P=0.0059), longer median total ischemia time (99 min, interquartile range: 71 – 144, vs. 77 min, interquartile range: 59 – 111, P=0.0309), and lower prevalence of ABO-incompatible transplantation (7.5% vs. 22.5%, P=0.0206) in patients with PCAR than in those without PCAR.Multivariate Cox regression analysis showed that development of PCAR was associated with allograft loss (Hazard Ratio=8.03, 95% Confidence Interval: 3.89 – 14.80, P

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Preserving Treg function: beyond mTOR inhibitors

No abstract available

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Biomarkers and kidney transplant: Time for a new paradigm?

No abstract available

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Effect of Conversion to CTLA4Ig Treatment on Tacrolimus-Induced Diabetic Rats

ABSTRACTBackgroundThe effect of conversion to cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig) treatment on tacrolimus (TAC)-induced renal dysfunction is well known, but its effect on TAC-induced diabetes mellitus (DM) is still undetermined. In the present study, we tested the diabetogenicity of CTLA4Ig and evaluated the effect of conversion to CTLA4Ig treatment on TAC-induced diabetic rats.MethodsWe tested diabetogenicity of CTLA4Ig by escalating doses (0.25, 0.5, 1, 2, and 4 mg/kg weekly) for 4 weeks. In the conversion study, we administered TAC (1.5 mg/kg) for 3 weeks and confirmed TAC-induced DM by intraperitoneal glucose tolerance test (IPGTT). Thereafter, TAC administration was continued, withdrawn, or replaced by CTLA4Ig treatment (1 or 2 mg/kg) for additional 3 weeks. The effect of CTLA4Ig on TAC-induced DM in vivo and in vitro was evaluated by assessing pancreatic islet function, histopathology, oxidative stress, apoptosis, and macrophage infiltration.ResultsIPGTT in the CTLA4Ig groups did not differ from the control group. In addition, plasma insulin level, glucose-induced insulin secretion, and islet viability were not different between the CTLA4Ig and control groups. In the conversion study, TAC withdrawal ameliorated pancreatic islet dysfunction compared to the TAC group, and conversion to CTLA4Ig further improved pancreatic islet function compared to the TAC withdrawal group. TAC-induced oxidative stress, apoptotic cell death, and infiltration of macrophages decreased with TAC withdrawal, and CTLA4Ig conversion further reduced those values. In the in vitro study, CTLA4Ig decreased TAC-induced pancreatic islet cell death and ROS production.ConclusionsCTLA4Ig was not diabetogenic, and conversion to CTLA4Ig reduced TAC-induced pancreatic islet injury. Background The effect of conversion to cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig) treatment on tacrolimus (TAC)-induced renal dysfunction is well known, but its effect on TAC-induced diabetes mellitus (DM) is still undetermined. In the present study, we tested the diabetogenicity of CTLA4Ig and evaluated the effect of conversion to CTLA4Ig treatment on TAC-induced diabetic rats. Methods We tested diabetogenicity of CTLA4Ig by escalating doses (0.25, 0.5, 1, 2, and 4 mg/kg weekly) for 4 weeks. In the conversion study, we administered TAC (1.5 mg/kg) for 3 weeks and confirmed TAC-induced DM by intraperitoneal glucose tolerance test (IPGTT). Thereafter, TAC administration was continued, withdrawn, or replaced by CTLA4Ig treatment (1 or 2 mg/kg) for additional 3 weeks. The effect of CTLA4Ig on TAC-induced DM in vivo and in vitro was evaluated by assessing pancreatic islet function, histopathology, oxidative stress, apoptosis, and macrophage infiltration. Results IPGTT in the CTLA4Ig groups did not differ from the control group. In addition, plasma insulin level, glucose-induced insulin secretion, and islet viability were not different between the CTLA4Ig and control groups. In the conversion study, TAC withdrawal ameliorated pancreatic islet dysfunction compared to the TAC group, and conversion to CTLA4Ig further improved pancreatic islet function compared to the TAC withdrawal group. TAC-induced oxidative stress, apoptotic cell death, and infiltration of macrophages decreased with TAC withdrawal, and CTLA4Ig conversion further reduced those values. In the in vitro study, CTLA4Ig decreased TAC-induced pancreatic islet cell death and ROS production. Conclusions CTLA4Ig was not diabetogenic, and conversion to CTLA4Ig reduced TAC-induced pancreatic islet injury. *Corresponding author: Chul Woo Yang, MD, Department of Internal Medicine, Seoul St. Mary's Hospital, 505 Banpo-Dong, Seocho-Ku, 137-040, Seoul, Republic of Korea. Fax: +82-2-536-0323, Phone: +82-2-2258-6037, E-mail: yangch@catholic.ac.kr Author's contributions: LJ contributed to the experimental surgeries, analyzed the data, and co-drafted the manuscript; JJ and KL performed the experiments and analyzed the data; SWL, EJK, BHC, and HLL retrieved and analyzed the data; SWL and CWY designed the study and co-drafted the manuscript. All authors read and approved the final manuscript. Disclosure: The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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History of marijuana use does not affect outcomes on the liver transplant waitlist

AbstractBackgroundData are limited on marijuana use and its impact on liver transplant (LT) waitlist outcomes. We aimed to assess the risk of waitlist mortality/delisting and likelihood of LT among prior marijuana users, and to determine the prevalence and factors associated with marijuana use.MethodsRetrospective cohort of adults evaluated for LT over 2 years at a large LT center. Marijuana use defined by self-report in psychosocial assessment and/or positive urine toxicology. Ongoing marijuana use was not permitted for LT listing during study period.Results884 adults were evaluated and 585 (66%) were listed for LT (median follow up 1.4 years, IQR 0.5-2.0). Prevalence of marijuana use was 48%, with 7% being recent users and 41% prior users. Marijuana use had statistically significant association with alcoholic cirrhosis (IRR=1.9) and hepatitis C (IRR=2.1) vs. hepatitis B, tobacco use (prior IRR=1.4; recent IRR=1.3 vs. never), alcohol use (never IRR 0.1; heavy use/abuse IRR 1.2 vs. social), and illicit drug use (prior IRR=2.3; recent =1.9 vs. never). In adjusted competing risk regression, marijuana use was not associated with the probability of LT (prior HR 0.9; recent HR=0.9 vs. never) or waitlist mortality/delisting (prior HR 1.0; recent HR 1.0 vs. never). However, recent illicit drug use was associated with higher risk of death or delisting (HR 1.8, p=0.004 vs. never).ConclusionsUnlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist. Prospective studies are needed to assess ongoing marijuana use on the LT waitlist and post-LT outcomes. Background Data are limited on marijuana use and its impact on liver transplant (LT) waitlist outcomes. We aimed to assess the risk of waitlist mortality/delisting and likelihood of LT among prior marijuana users, and to determine the prevalence and factors associated with marijuana use. Methods Retrospective cohort of adults evaluated for LT over 2 years at a large LT center. Marijuana use defined by self-report in psychosocial assessment and/or positive urine toxicology. Ongoing marijuana use was not permitted for LT listing during study period. Results 884 adults were evaluated and 585 (66%) were listed for LT (median follow up 1.4 years, IQR 0.5-2.0). Prevalence of marijuana use was 48%, with 7% being recent users and 41% prior users. Marijuana use had statistically significant association with alcoholic cirrhosis (IRR=1.9) and hepatitis C (IRR=2.1) vs. hepatitis B, tobacco use (prior IRR=1.4; recent IRR=1.3 vs. never), alcohol use (never IRR 0.1; heavy use/abuse IRR 1.2 vs. social), and illicit drug use (prior IRR=2.3; recent =1.9 vs. never). In adjusted competing risk regression, marijuana use was not associated with the probability of LT (prior HR 0.9; recent HR=0.9 vs. never) or waitlist mortality/delisting (prior HR 1.0; recent HR 1.0 vs. never). However, recent illicit drug use was associated with higher risk of death or delisting (HR 1.8, p=0.004 vs. never). Conclusions Unlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist. Prospective studies are needed to assess ongoing marijuana use on the LT waitlist and post-LT outcomes. Corresponding Author: Prashant Kotwani, MD, Email – prashant.kotwani@ucsf.edu; prashant.kotwani@gmail.com, 505 Parnassus Avenue, Room 987, San Francisco, CA 94143, Phone: 415-476-1528, Fax: 415-502-1976 Authorship PK - contributed to research design, data collection, data analysis, manuscript preparation VS – contributed to research design, data analysis, manuscript preparation JLD – contributed to data analysis, manuscript preparation JR – contributed to research design, manuscript preparation FY – contributed to research design, manuscript preparation BH – contributed to research design, data analysis, manuscript preparation Conflict of Interest The authors declare no conflicts of interest Funding This work was supported, in part, by the Biostatistics Core of the UCSF Liver Center (P30 DK026743). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Liver transplantation for NASH-related hepatocellular carcinoma versus non-NASH etiologies of hepatocellular carcinoma

AbstractBackgroundLiver Transplant (LT) for Non-Alcoholic Steatohepatitis (NASH) related Hepatocellular Carcinoma (HCC) is not well characterized in the literature. The aim of the study was to examine characteristics and outcomes of patients who had LT for NASH-HCC (NASH) vs. HCC from other liver diseases (non-NASH).MethodsUsing a two-centre retrospective design all patients from 2004-2014 that received LT for HCC were analyzed. Subgroup analysis stratified patients according to Milan criteria.Results929 patients were transplanted for HCC. 60/929 (6.5%) had HCC in the context of NASH. There were no significant differences between groups for pretransplant or explant tumor characteristics. The actuarial 1-, 3- and 5-year overall survival was 98%, 96% and 80% in NASH vs. 95%, 84% and 78% in non-NASH (p=0.1). No differences in tumor recurrence were observed in patients within and beyond Milan in the NASH group. Multivariate Cox Regression demonstrated NASH status to be a protective factor for recurrence among patients with tumors beyond Milan, HR 0.21 (0.05-0.86), p=0.029.ConclusionAfter LT, outcomes are similar between NASH and non-NASH etiologies for HCC. The hypothesis that patients with more advanced HCC tumors in the context of NASH may have more favourable outcomes after LT has been generated, but requires further study. Background Liver Transplant (LT) for Non-Alcoholic Steatohepatitis (NASH) related Hepatocellular Carcinoma (HCC) is not well characterized in the literature. The aim of the study was to examine characteristics and outcomes of patients who had LT for NASH-HCC (NASH) vs. HCC from other liver diseases (non-NASH). Methods Using a two-centre retrospective design all patients from 2004-2014 that received LT for HCC were analyzed. Subgroup analysis stratified patients according to Milan criteria. Results 929 patients were transplanted for HCC. 60/929 (6.5%) had HCC in the context of NASH. There were no significant differences between groups for pretransplant or explant tumor characteristics. The actuarial 1-, 3- and 5-year overall survival was 98%, 96% and 80% in NASH vs. 95%, 84% and 78% in non-NASH (p=0.1). No differences in tumor recurrence were observed in patients within and beyond Milan in the NASH group. Multivariate Cox Regression demonstrated NASH status to be a protective factor for recurrence among patients with tumors beyond Milan, HR 0.21 (0.05-0.86), p=0.029. Conclusion After LT, outcomes are similar between NASH and non-NASH etiologies for HCC. The hypothesis that patients with more advanced HCC tumors in the context of NASH may have more favourable outcomes after LT has been generated, but requires further study. Corresponding Author: Dr. Gonzalo Sapisochin, Multi-Organ Transplant. Division of General Surgery, Department of Surgery, University of Toronto, 585 University Avenue, 11-PMB-184, Toronto, ON M5G 2N2, Canada. gonzalo.sapisochin@uhn.ca. T: +1 416 340 5230, F: +1 416 340 5242 Authorship E.M. Sadler - involved in study design, data collation, data analysis, manuscript preparation. N. Mehta – involved in study design, data collection, data analysis, and manuscript review. M. Bhat – involved in study design, manuscript preparation and review. A. Ghanekar – involved in data collection and manuscript review. P.D. Greig – involved in data collection and manuscript review. D.R. Grant – involved in data collection and manuscript review. F. Yao – involved in study design, data collection, and manuscript review. G. Sapisochin – involved in study design, data collection, data analysis, manuscript review. Disclosure The authors declare no conflict of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Selective CD28 inhibition modulates alloimmunity and cardiac allograft vasculopathy in anti-CD154-treated monkeys

AbstractBackgroundSelective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade.MethodsCynomolgus monkey heterotopic cardiac allograft recipients received sc28AT (10 mg/kg, d0-20, n=3), hu5C8 (10-30 mg/kg, d0-84, n=4), or combination (n=6). Graft survival was monitored by telemetry. Protocol biopsies and graft explants were graded according to ISHLT AR and CAV scores. Alloantibody, T cell phenotype and Tregs were analyzed by flow cytometry. Immunochemistry and gene expression (Nanostring) characterized intra-graft cellular infiltration.ResultsRelative to modest prolongation of median graft survival time with sc28AT alone (34 days), hu5C8 (133 days) and sc28AT+hu5C8 (141 days) prolonged survival to a similar extent. CD28 blockade at induction, added to hu5C8, significantly attenuated the severity of acute rejection and cardiac allograft vasculopathy (CAV) during the first 3 months after transplantation relative to hu5C8 alone. These findings were associated with decreased proportions of circulating CD8+ and CD3+CD28- T cells, and modulation of inflammatory gene expression within allografts.ConclusionsInduction with sc28AT promotes early cardiac allograft protection in hu5C8-treated NHPs. These results support further investigation of prolonged selective CD28 inhibition with CD40/CD154 blockade in NHP transplants. Background Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade. Methods Cynomolgus monkey heterotopic cardiac allograft recipients received sc28AT (10 mg/kg, d0-20, n=3), hu5C8 (10-30 mg/kg, d0-84, n=4), or combination (n=6). Graft survival was monitored by telemetry. Protocol biopsies and graft explants were graded according to ISHLT AR and CAV scores. Alloantibody, T cell phenotype and Tregs were analyzed by flow cytometry. Immunochemistry and gene expression (Nanostring) characterized intra-graft cellular infiltration. Results Relative to modest prolongation of median graft survival time with sc28AT alone (34 days), hu5C8 (133 days) and sc28AT+hu5C8 (141 days) prolonged survival to a similar extent. CD28 blockade at induction, added to hu5C8, significantly attenuated the severity of acute rejection and cardiac allograft vasculopathy (CAV) during the first 3 months after transplantation relative to hu5C8 alone. These findings were associated with decreased proportions of circulating CD8+ and CD3+CD28- T cells, and modulation of inflammatory gene expression within allografts. Conclusions Induction with sc28AT promotes early cardiac allograft protection in hu5C8-treated NHPs. These results support further investigation of prolonged selective CD28 inhibition with CD40/CD154 blockade in NHP transplants. * T.Z. and A.M.A. contributed equally to the first authorship of this study. #Correspondence: Richard N. Pierson III, MD, Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, 110 South Paca Street 7N-134, Baltimore, MD 21201. E-mail: rpierson@som.umaryland.edu. Phone: 410.328.5842, Fax: 410.328.2750 Authorship Contributions: T.Z., A.M.A., and R.N.P.III designed the experiments, analysed the data, and wrote the article. W.S., N.A.O., E.B., and G.B. performed experiments and analysed data. E.S., L.B., X.C., T.M., S.D., D.H., E.R., E.W., A.K., and C.A. conducted all experiments. Disclosure : The authors declare no conflict of interest. Funding: This work was supported by the NIH (UO1 AI 066719), an ASTS Mid-Career Award, a contract from the DOD ORD (N00014-04-1-0821), and an AHA Grant-in-Aid, all to RNP; by the Other Tobacco Related Diseases research grant from the Maryland Restitution Fund Program, to AA and RNP; and by the NIH Nonhuman Primate Reagent Resource (OD010976 and AI126683). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A high portal venous pressure gradient increases gut-related bacteremia and consequent early mortality after living donor liver transplantation

AbstractBackgroundPortal hypertension (PHT) is defined as a portal venous pressure gradient (PVPG) exceeding 5 mmHg, which results in severe clinical manifestations. However, the validity of intraoperative PVPG monitoring and the association between PHT and bacterial translocation (BT) after liver transplantation remain unclear.MethodsIn this retrospective study, 223 patients who underwent primary adult-to-adult living donor liver transplantation (ALDLT) from 2008 to 2015 were divided into 2 groups based on the PVPG at the end of the operation: high PVPG (>5 mmHg, n=69) and low PVPG (≤5 mmHg, n=154). The clinical factors were compared between the groups, and the association between a high PVPG and posttransplant bacteremia/bacterial infections was investigated.ResultsThe high PVPG group had a significantly higher incidence of bacteremia (46% vs. 24%, p<.001 higher mortality rate vs. p=".002)," and poorer survival the high pvpg group had a particularly incidence of bacteremia caused by bacteria including enterobacteriaceae bacteroides spp. enterococcus multivariate analysis showed that>5 mmHg (odds ratio, 2.55; 95% confidence interval, 1.18–5.55; p=.017) was an independent predictor of bacteremia due to gut bacteria.ConclusionsMonitoring of the PVPG is clinically meaningful for predicting patients' prognosis. In particular, a high PVPG with a threshold of 5 mmHg at the end of ALDLT may increase gut-related bacteremia through the mechanism of BT, resulting in early mortality. Background Portal hypertension (PHT) is defined as a portal venous pressure gradient (PVPG) exceeding 5 mmHg, which results in severe clinical manifestations. However, the validity of intraoperative PVPG monitoring and the association between PHT and bacterial translocation (BT) after liver transplantation remain unclear. Methods In this retrospective study, 223 patients who underwent primary adult-to-adult living donor liver transplantation (ALDLT) from 2008 to 2015 were divided into 2 groups based on the PVPG at the end of the operation: high PVPG (>5 mmHg, n=69) and low PVPG (≤5 mmHg, n=154). The clinical factors were compared between the groups, and the association between a high PVPG and posttransplant bacteremia/bacterial infections was investigated. Results The high PVPG group had a significantly higher incidence of bacteremia (46% vs. 24%, p<.001 higher mortality rate vs. p=".002)," and poorer survival the high pvpg group had a particularly incidence of bacteremia caused by bacteria including enterobacteriaceae bacteroides spp. enterococcus multivariate analysis showed that>5 mmHg (odds ratio, 2.55; 95% confidence interval, 1.18–5.55; p=.017) was an independent predictor of bacteremia due to gut bacteria. Conclusions Monitoring of the PVPG is clinically meaningful for predicting patients' prognosis. In particular, a high PVPG with a threshold of 5 mmHg at the end of ALDLT may increase gut-related bacteremia through the mechanism of BT, resulting in early mortality. Corresponding author: Shintaro Yagi, Ph.D., Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Telephone: +81-75-751-3242; FAX: +81-75-751-4263; E-mail: shintaro@kuhp.kyoto-u.ac.jp Authorship S.Yao and S.Yagi designed the study and wrote the draft. S.Yao, T.Iida, and Y.Okamura acquired the data. M.Nagao analyzed the data as a specialist of infection prevention. R.Uozumi analyzed the data as a specialist of medical statistician. S. Yagi, T. Iida, Y.Okamura, T.Anazawa, H.Okajima, T.Kaido and S.Uemoto performed living-donor liver transplantations, followed up the patients. M.Nagao, T.Anazawa, H.Okajima, T.Kaido, S.Uemoto contributed to editing the manuscript. S.Uemoto supervised the study design and revised the manuscript. Disclosures The authors have no conflicts of interest or financial ties to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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B Cells in Transplantation: of rat, mouse and man

No abstract available

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Long-term outcome of one-step kidney transplantation and bladder augmentation procedure in pediatric patients

ABSTRACTBackgroundGuidelines for bladder augmentation (BA) in kidney transplant (KT) recipients are not well-defined. In our center, simultaneous BA with KT (BA-KT) is performed. We assessed transplantation outcomes of this unique extensive procedure.MethodsA case-control single center retrospective study. Transplantation outcomes were compared with those of KT recipients who did not need BA.ResultsCompared to 22 patients who underwent KT only, for 9 who underwent BA-KT, surgical complications and the need for revision in the early posttransplantation period were similar; early graft function was better: estimated glomerular filtration rate (eGFR): 96.5±17.1 vs. 79.4±16.6 ml/min at 0-6 months (p=0.02); posttransplantation clean intermittent catheterization was more often needed: by 78% (7/9) vs. 13% (3/22); and asymptomatic bacteriuria was more common: 100% vs. 9% during the first 6 months (P

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Early Hospital Readmission: The Canary in the Coal Mine?

No abstract available

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Publication Rates of Oral Abstract Presentations at the 2014 International Congress of the Transplantation Society

No abstract available

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Opioid Prescription, Morbidity, and Mortality in US Transplant Recipients

ABSTRACTBackgroundCDC guidelines recommend caution in prescribing opioids for chronic pain. The characteristics of opioid prescription (OpRx) among kidney transplant (KTx) recipients has not been described in a national population.MethodsWe assessed OpRx prevalence among prevalent KTx recipients, and associated duration (chronic, defined as ≥90 days in a year) and dosing (in morphine milligram equivalents per day, MME, of

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Heart Transplantation in a Left Ventricular Assist Device Recipient Following Donor's Extracorporeal Membrane Oxygenation Support: Is it safe?

No abstract available

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Patterns of Discordance Between Pretransplant Imaging Stage of Hepatocellular Carcinoma and Posttransplant Pathologic Stage: A Contemporary Appraisal of the Milan Criteria

AbstractBackgroundPatients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood.MethodsPatients who underwent orthotopic liver transplantation (OLT) for HCC following preoperative MRI were identified in a prospectively collected institutional database (1/2003-12/2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were utilized to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival.ResultsOf 318 patients with HCC meeting Milan criteria by MRI at the time of OLT, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 vs. 140.0 months, p=0.002) and overall survival (96.0 vs. 143.0 months, p=0.005), and did not vary between patients exceeding criteria due to tumor explant >5 cm, >3 tumor foci, or a tumor >3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum AFP level (OR 2.82, 95% CI 1.37-5.79, p=0.005).ConclusionsUnderestimating HCC burden prior to liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing AFP prior to transplantation may benefit from more frequent testing or novel neoadjuvant therapies. Background Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood. Methods Patients who underwent orthotopic liver transplantation (OLT) for HCC following preoperative MRI were identified in a prospectively collected institutional database (1/2003-12/2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were utilized to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival. Results Of 318 patients with HCC meeting Milan criteria by MRI at the time of OLT, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 vs. 140.0 months, p=0.002) and overall survival (96.0 vs. 143.0 months, p=0.005), and did not vary between patients exceeding criteria due to tumor explant >5 cm, >3 tumor foci, or a tumor >3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum AFP level (OR 2.82, 95% CI 1.37-5.79, p=0.005). Conclusions Underestimating HCC burden prior to liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing AFP prior to transplantation may benefit from more frequent testing or novel neoadjuvant therapies. Corresponding Author: Matthew H. Levine, MD, PhD, 3400 Spruce Street, 1 Founders, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Phone: 215.662.7367. E-mail: matthew.levine@uphs.upenn.edu. Author contributions: 1) conception and design (Ecker, Hoteit, Shaked, Olthoff, Levine), acquisition of data (Ecker), or analysis and interpretation of data (all authors); 2) drafting (Ecker, Levine) or revising (all authors) 3) final approval of the version to be published (all authors) Disclosures: The authors report no conflicts of interest Funding: none Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia

Background and Objectives Dosage of local anesthetics (LAs) used for regional anesthesia in children is not well determined. In order to evaluate and come to a consensus regarding some of these controversial topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Methods Representatives from both ASRA and ESRA composed the joint committee practice advisory. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Results Spinal anesthesia with bupivacaine can be performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5 mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for spinal anesthesia (dose, 0.07–0.13 mL/kg). Ultrasound-guided upper-extremity peripheral nerve blocks (eg, axillary, infraclavicular, interscalene, supraclavicular) in children can be performed successfully and safely using a recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg. Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral nerve blocks in children. Conclusions High-level evidence is not yet available to guide dosage of LA used in regional blocks in children. The ASRA/ESRA recommendations intend to provide guidance in order to reduce the large variability of LA dosage currently observed in clinical practice. Accepted for publication August 20, 2017. Address correspondence to: Santhanam Suresh, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Chicago, IL 60611 (e-mail: ssuresh@luriechildrens.org). Identification of institution(s) where work is attributed: Ann & Robert H. Lurie Children's Hospital of Chicago Northwestern University, Chicago, IL; and Department of Anesthesiology at Rhode Island Hospital, Alpert School of Medicine, Brown University, Providence, RI. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Epidural Hematoma Following Interlaminar Epidural Injection in Patient Taking Aspirin

Objective We present a case report of a patient who developed an epidural hematoma following an interlaminar epidural steroid injection with no risk factors aside from old age and aspirin use for secondary prevention. Case Report A 79-year-old man developed an epidural hematoma requiring surgical treatment following an uncomplicated interlaminar epidural steroid injection performed for neurogenic claudication. In the periprocedural period, he continued aspirin for secondary prophylaxis following a myocardial infarction. Conclusions For patients taking aspirin for primary or secondary prophylaxis, the American Society of Regional Anesthesia and Pain Medicine antiplatelet and anticoagulation guidelines for spine and pain procedures recommend a shared assessment and risk stratification when deciding to hold the medication for intermediate-risk neuraxial procedures. Cases such as this serve to highlight the importance of giving careful consideration to medical optimization of a patient even when a low- or intermediate-risk procedure is planned. Accepted for publication September 2, 2017. Address correspondence to: Rebecca A. Sanders, MD, 200 First Street SW, Rochester, MN 55901 (e-mail: Sanders.rebecca@mayo.edu). The authors declare no conflict of interest. A case abstract was presented at the 2016 Annual Meeting of the American Academy of Pain Medicine; February 18 to 21, 2016; Palm Springs, CA. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

http://ift.tt/2CYY4Ed

A Comparative Evaluation of Changes in Soft Tissues After Single-Jaw Surgery and Bimaxillary Surgery in Skeletal Class III Patients

Abstract

Aims and Objectives

The aim of this study was to compare cephalograms for the hard and soft tissue changes observed in skeletal Class III patients of Indian origin who had undergone either single-jaw mandibular setback (BSSO) or bimaxillary surgery (Le Fort I advancement + BSSO setback) and also to derive a correlation between the changes brought about in the soft tissues by the surgical alteration in hard tissue.

Materials and Methods

The study included records comprising 18 treated skeletal Class III patients, who were divided into two groups based on the surgical procedures advocated: Group I: single-jaw procedure comprised of only mandibular set back, Group II: bimaxillary surgery. Presurgical and post-treatment cephalograms were calibrated and traced using Ilexis FACAD AB-2014 Version 3.8.0.0 software and analyzed with COGS hard tissue analysis and soft tissue analysis. All values for the hard tissue and soft tissue measurements were compared with the norms prescribed for the Indian population.

Results

Upper lip changes were evident in both groups but greater significance was observed in bi-jaw group. Single-jaw patients showed positive correlation for hard to soft tissue mandibular position. Bi-jaw surgical cases exhibited positive correlations between changes Wits variable to soft tissue convexity as well as mandibular position.

Conclusion

The soft tissues changes between Class III patients treated by single-jaw surgery and those treated by bimaxillary surgery when compared revealed that significant differences were observed only in relation to certain measurements such as facial convexity, maxillary prognathism, and upper lip protrusion.

http://ift.tt/2DgDH2o

Prone Position, Cerebral Oximetry, and Delirium

No abstract available

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Management of Morgellons Disease With Low-Dose Trifluoperazine

This medical record review examines the novel use of low-dose trifluoperazine, a high-potency typical antipsychotic, in a cohort of patients with Morgellons disease.

http://ift.tt/2DhpHpb

Diagnosis of Neurofibromatosis Type 2 From Congenital Skin Plaques

This genetic testing study reports a case of an early diagnosis of neurofibromatosis type 2 (NF2) in a child after genetic analysis of congenital skin plaques, with confirmation of these findings by analysis of skin plaques from 6 unrelated patients with NF2.

http://ift.tt/2CMAtT3

Intertriginous Condyloma-like Plaques and Ulcers

A woman in her 50s with a medical history of hypertension and depression was evaluated by the inpatient dermatology consult service for a 1.5-year history of painful intertriginous wounds; she was previously diagnosed with hidradenitis suppurativa. What is your diagnosis?

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Human Herpesvirus 8–Associated Inflammatory Cytokine Syndrome

This case report describes a patient with human herpesvirus 8–associated inflammatory cytokine syndrome.

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Comorbidity Development in Children With Psoriasis

This cohort study examines the risk ocomorbidities in children with and without psoriasis, after accounting for obesity.

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COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation

Thyroid , Vol. 0, No. 0.

http://ift.tt/2qPDznR

Allergen Concerns and Popular Skin Care Products

To the Editor We read with great interest the article by Xu et al published in a recent issue of JAMA Dermatology highlighting the high prevalence of contact allergens in common moisturizers. Their data mirror similar results in our recent study investigating contact allergens in pediatric personal care products marketed as hypoallergenic, dermatologist recommended and/or tested, fragrance free, or paraben free. Similar to the study by Xu et al, which found that 88% of common moisturizers contained at least 1 common contact allergen, we found that 167 of 187 of our selection of pediatric products (89%) contained at least 1 allergen.

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Vegetating Darier Disease Treated With Botulinum Toxin

This case report describes a patient with vegetating Darier disease treated with botulinum toxin.

http://ift.tt/2ANBxpn

Dermatology Practice Consolidation Fueled by Private Equity Investment

This Viewpoint discusses the consolidation of dermatology practices facilitated by private equity investment and the potential consequences for the specialty and patients.

http://ift.tt/2zVEF4m

Dermatology’s Grandest Piano

This is a story about a piano that played a small but special role in dermatology's history. It belonged to Stephen Rothman, MD (1894-1963), one of the most influential dermatologists of the 20th century. He was also an accomplished pianist.

http://ift.tt/2Dk3XsR

The Importance of Population-Based Estimates of Melanocytic Pathology

In this issue of JAMA Dermatology, Lott et al describe a novel and innovative approach to estimating the prevalence of different types of melanocytic lesions in all adults undergoing skin biopsies in a population. Using an automated natural language processing tool, they analyzed 80 368 written pathology reports of skin biopsies from 47 529 adult patients drawn from an underlying health system patient population, which was representative of the general adult population. For analysis of each pathology report, the diagnosis was first dichotomized as either a melanocytic or nonmelanocytic lesion. For melanocytic lesions, the cases were then assigned to 1 of 4 diagnostic categories based on the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx), with differing management implications: class I, benign lesion requiring no further treatment; class II, low-risk lesion requiring complete excision with narrow (<5-mm) margins; class III, higher-risk lesion such as melanoma in situ requiring reexcision with 5-mm to 1-cm margins; and class IV/V, invasive melanoma requiring wide reexcision with 1-cm margins or greater. Approximately one-quarter of all skin biopsies were of melanocytic lesions. Of these, over 90% were benign or low risk (class I or II); 4.5% were melanoma in situ or similar-risk lesion (class III); and 4.1% were invasive melanoma (class IV/V).

http://ift.tt/2z4T1zp

Hair Repigmentation With Anti–PD-1 and Anti–PD-L1 Immunotherapy

To the Editor We read with great interest the article by Rivera and colleagues reporting on hair repigmentation in patients receiving immunotherapy with anti–programmed cell death 1 (PD-1) and anti–programmed cell death 1 ligand 1 (PD-L1) immunotherapy.

http://ift.tt/2jMSX1k

Population-Based Frequencies and Distribution of Melanocytic Lesions

This large-scale analysis of pathology reports in electronic medical records, using the natural language processing technique, evaluates population-based distributions and pathologic characteristics of melanocytic proliferations.

http://ift.tt/2z4G7Pu

Spanish Fly—Cantharidin’s Alter Ego

Cantharidin, derived from the Greek word for beetle, kantharis, is an odorless, colorless terpenoid produced by up to 2000 species of beetles collectively referred to as blister beetles. Male blister beetles synthesize and use cantharidin as a defensive chemical and nuptial gift. Females receive cantharidin during mating and use the compound to coat their eggs to ward off predators. It functions as a potent vesicant on skin contact, but it is also a systemic poison if ingested, with toxic effects comparable with those of strychnine and cyanide. If properly dosed and applied, however, its blistering properties can be used therapeutically.

http://ift.tt/2DfvWJR

Geographic Distribution of Nonphysicians Who Billed Medicare for Dermatologic Services

This study uses Medicare and US Census data to discover which dermatology-related services are independently billed by nonphysician clinicians treating Medicare beneficiaries, and where these clinicians are located.

http://ift.tt/2jRq9ox

Topical Timolol for Paronychia and Pseudopyogenic Granuloma

This study evaluated the efficacy and tolerability of topical timolol, 0.5%, gel as a treatment of paronychia and pseudopyogenic granuloma induced by antineoplastic agents.

http://ift.tt/2yIqD72

Probiotic Strains for Children With Moderate Atopic Dermatitis

This randomized clinical trial investigates whether a mixture of oral probiotics is safe and effective in the treatment of atopic dermatitis symptoms and evaluates its influence on the use of topical steroids in children.

http://ift.tt/2m5oMDc

Treatment of Refractory Mycosis Fungoides With Brentuximab Vedotin

This case report describes the treatment of CD30-negative refractory mycosis fungoides with brentuximab vedotin.

http://ift.tt/2jMkkZj

Factors Associated With Remission of Skin Disease in Dermatomyositis

This cohort study examines factors associated with clinical remission of skin disease in dermatomyositis.

http://ift.tt/2AgVAeH

Hair Repigmentation With Anti–PD-1 and Anti–PD-L1 Immunotherapy—Reply

In Reply We read with interest the letter by Manson et al. They describe another case of hair repigmentation (HR) in a male patient with concomitant advanced colorectal cancer and Hodgkin lymphoma treated with nivolumab and showing a good response. Interestingly, this new case seems to support the association between a good response and HR.

http://ift.tt/2hU43AZ

Preference-Based QOL Measures for Economic Evaluations in Early Melanoma

This study uses randomized clinical trial data to compare utility scores from the AQoL-8D and the FACT-M and evaluate the sensitivity of both instruments in identifying the influence of fear of cancer recurrence on health-related quality of life in patients with early-stage melanoma.

http://ift.tt/2zBoM03

Error in Figure Legend

In the article titled "Factors Associated With Clinical Remission of Skin Disease in Dermatomyositis" by Wolstencroft et al, published online November 7, 2017, there was an error in the key for Figure 1B. This article was corrected online.

http://ift.tt/2DjIznu

Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients

This cohort study addresses whether current skin surveillance intervals and threshold for biopsy of suspicious lesions are adequate for the increased tendency of solid organ transplant recipients to develop potentially aggressive cutaneous squamous cell carcinomas.

http://ift.tt/2hW3C9v

Sporty Spots

During the 2016 summer Olympic Games in Rio de Janeiro, Brazil, many viewers questioned the origins of the purple spots seen on US swimmer Michael Phelps during a relay event. Similarly, in recent years public attention has been drawn to the tell-tale circular markings on various other celebrities' bodies, including Justin Bieber, Jennifer Aniston, and Gwyneth Paltrow. The origin of these markings is an ancient practice called "cupping," which uses suction to attach a cup to skin for purported therapeutic benefit. In recent times, the practice has been popularized in the United States as a form of complementary and alternative medicine (CAM) practice.

http://ift.tt/2DjImkc

Tanning Salon Compliance in States With Legislation to Protect Youth Access

This cross-sectional telephone survey investigates compliance rates in the 42 states and the District of Columbia with legislation restricting tanning bed use in minors.

http://ift.tt/2xnRW1G

January 2018 Issue Highlights

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Chronisch spontane Urtikaria

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Operative Behandlungsoptionen bei Hidradenitis suppurativa/Acne inversa

Zusammenfassung

Hidradenitis suppurativa/Acne inversa (HS/AI) ist eine chronisch inflammatorische Hauterkrankung, für deren Behandlung konservative und operative Therapieoptionen zur Verfügung stehen. Im Hurley-Stadium II und III stellt die operative Sanierung von irreversibel destruiertem Gewebe die Methode der Wahl dar. Resektionstechniken unterschiedlicher Invasivität werden in der Literatur beschrieben. Bisher herrscht kein allgemein akzeptierter Konsens über den Einsatz verschiedener Resektions- und Rekonstruktionstechniken sowie die postoperative Nachbehandlung. Die Beurteilung von Rezidiven nach chirurgischer Intervention wird durch fehlende Rezidivdefinitionen sowie eine heterogene Studienlage erschwert.

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Panorama Dermatologische Praxis

http://ift.tt/2qPuBqS

Evaluation of the Thyroid Volume After Radiofrequency Ablation of Thyroid Nodules and Recurrent Thyroid

Condition: Thyroid Nodule
Intervention: Device: Celon Pro Surge
Sponsor: Olympus Surgical Technologies Europe
Recruiting

http://ift.tt/2AM3H2N

Avenir® Cemented Hip Stem - PMCF

Conditions: Primary Osteoarthritis; Post-Traumatic Osteoarthritis of Hip; Femoral Neck Fractures; Femoral Head Necrosis; Sequelae From Previous Hip Surgery; Osteotomies; Congenital Hip Dysplasia
Intervention:
Sponsor: Zimmer Biomet
Recruiting

http://ift.tt/2D0EYNY

The Association Between Serum Vaspin and Omentin-1 Levels in Obese Children with Metabolic Syndrome

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.

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In Vivo and Ex Vivo Inflammatory Markers of Common Metabolic Phenotypes in Humans

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.

http://ift.tt/2mgRL3T

Interaction of Metabolic Health and Obesity on Subclinical Target Organ Damage

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.

http://ift.tt/2D0p9Gn

Head circumference - a useful single parameter for skull volume development in cranial growth analysis?

Abstract

Background

The measurement of maximal head circumference is a standard procedure in the examination of childrens' cranial growth and brain development. The objective of the study was to evaluate the validity of maximal head circumference to cranial volume in the first year of life using a new method which includes ear-to-ear over the head distance and maximal cranial length measurement.

Methods

3D surface scans for cranial volume assessment were conducted in this method comparison study of 44 healthy Caucasian children (29 male, 15 female) at the ages of 4 and 12 months.

Results

Cranial volume increased from measurements made at 4 months to 12 months of age by an average of 1174 ± 106 to 1579 ± 79 ml. Maximal cranial circumference increased from 43.4 ± 9 cm to 46.9 ± 7 cm and the ear-to ear measurement increased from 26.3 ± 21 cm to 31.6 ± 18 cm at the same time points. There was a monotone association between maximal head circumference (HC) and increase in volume, yet a backwards inference from maximal circumference to the volume had a predictive value of only 78% (adjusted R²). Including the additional measurement of distance from ear to ear strengthened the ability of the model to predict the true value attained to 90%. The addition of the parameter skull length appeared to be negligible.

Conclusion

The results demonstrate that for a distinct improvement in the evaluation of a physiological cranial volume development, the additional measurement of the ear-to ear distance using a measuring tape is expedient, and, especially for cases with pathological skull changes, such as craniosynostosis, ought to be conducted.

http://ift.tt/2CVnRwp

Similar localization of conformational IgE epitopes on the house dust mite allergens Der p 5 and Der p 21 despite limited IgE-cross-reactivity

Abstract

Background

Due to high IgE recognition frequency and high allergenic activity, Der p 5 and Der p 21 are clinically important house dust mite (HDM) allergens. The objective of this study was to characterise the immunodominant IgE epitopes of Der p 5 and Der p 21 responsible for their high allergenic activity.

Methods

A panel of 12 overlapping peptides spanning the Der p 5 and Der p 21 sequence were synthesized to search for sequential IgE epitopes by direct testing for allergic patients ' IgE reactivity. Peptide-specific antibodies raised in rabbits were used in inhibition studies for localizing conformational IgE epitopes which were visualized on the surfaces of the allergen structures by molecular modelling. IgE cross-reactivity between the allergens was studied by IgE inhibition studies.

Results

Immunodominant IgE epitopes defined by allergic patients' IgE on Der p 5 and Der p 21 were primarily of the conformational, discontinuous type including N- and C-terminal portions of the protein. They could be located on each allergen on one area with similar localization but despite similar structure of the allergens no relevant IgE cross-reactivity could be detected.

Conclusion

Our study shows that Der p 5 and Der p 21 contain a major conformational IgE epitope-containing area located on similar portions of their structure but they lack relevant IgE cross-reactivity. These data are important for the development of modern allergy vaccines based on defined molecules for allergen-specific immunotherapy of HDM allergy.

http://ift.tt/2mkShP9

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

Abstract

Background

Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM-allergoids administered sublingually in comparison to native allergens.

Methods

Three immunization protocols (4-8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells.

Results

A quick antibody response and higher IgG2a/IgE ratio was observed with PM-allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL-4 ratio with a quick IL-10 production by submandibular LN cells. An increase of CD4⁺CD25^highFOXP3⁺ Treg cells was detected in LNs and spleen of mice treated with PM-allergoids. These allergoids were better captured than native allergens by antigen presenting (CD45⁺MHC-II⁺) cells obtained from the sublingual mucosa, including DCs (CD11b⁺) and macrophages (CD64⁺). Importantly, all the differential effects induced by PM-allergoids were abolished when using oxidized instead of nonoxidized PM-allergoids.

Conclusion

Our results demonstrate for the first time that PM-allergoids administered through the sublingual route promote the generation of Th1 and FOXP3⁺ Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen presenting cells.

http://ift.tt/2qLmlrC

Skin inflammation exacerbates food allergy symptoms in epicutaneously sensitized mice

Abstract

Background

Cutaneous exposure to food antigen through impaired skin barrier has been shown to induce epicutaneous sensitization, thereby causing IgE-mediated food allergies.

Objective

We examined whether skin barrier impairment following epicutaneous sensitization exacerbates food allergies.

Methods

BALB/c mice were epicutaneously sensitized by repeated application of ovalbumin (OVA) to MC903-pretreated ear skin for 48 hours weekly and then intragastrically challenged with OVA. After the first oral challenge, the skin barrier was disrupted with topical application of MC903 or by tape-stripping. Mice were monitored for changes in body temperature and the occurrence of diarrhea after undergoing the second oral challenge. Serum levels of mouse mast cell protease-1 (mmcp1) and OVA-specific IgE, IgG1, IgG2a antibodies and OVA-specific IgA levels in intestinal lavage fluid were measured by ELISA. Tissue accumulation of eosinophils was determined histologically.

Results

Epicutaneously sensitized mice developed anaphylaxis after intragastric challenge, as evidenced by diarrhea, decreased body temperature and increased serum mmcp1 levels. Skin barrier disruption by MC903 treatment or tape-stripping exacerbated allergic reactions induced by oral challenge. MC903 treatment increased serum baseline and post-challenge mmcp1 levels. Topical pretreatment with dexamethasone alleviated allergic reactions that were exacerbated by MC903-treatement.

Conclusion

Even after eliminating exposure to the antigen, inflammation from skin barrier disruption can exacerbate the severity of food allergy symptoms. Serum baseline mmcp1 levels might be an effective marker for predicting the severity of antigen-induced allergic symptoms.

http://ift.tt/2mkJ8pS

Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells

Abstract

Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy (SLIT) has showed promise, combined therapy may be necessary to achieve a strong and long-term tolerance. In this work, we combined SLIT with systemic administration of IL-2 associated with an anti-IL-2 monoclonal antibody (IL-2/anti-IL-2Ab complex or IL-2C) to reverse the IgE-mediated experimental allergy.

Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions. Then, allergic mice were treated with a sublingual administration of very low amounts of milk proteins combined with intraperitoneal injection of low doses of IL-2C. The animals were next re-exposed to allergens and mucosal as well as systemic immunological parameters were assessed in vivo and in vitro.

The treatment reduced serum specific IgE, IL-5 secretion by spleen cells and increased IL-10 and TGF-β in the lamina propria of buccal and duodenal mucosae. We found an augmented frequency of IL-10-secreting CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg) in the submaxilar lymph nodes and buccal lamina propria. Tregs were sorted, characterized and adoptively transferred to naïve mice, which were subsequently sensitized. No allergy was experienced in these mice and we encouragingly discovered a faster and more efficient tolerance induction with the combined therapy compared with SLIT.

In conclusion, the combination of two therapeutic strategies rendered Treg-mediated tolerance more efficient compared to individual treatments and reversed the established IgE-mediated food allergy. This approach highlights the ability of IL-2C to expand Tregs, and it may represent a promising disease-modifying therapy for managing food allergy.

http://ift.tt/2qQelFT

IL-37 inhibits IL-4/IL-13-induced CCL11 production and lung eosinophilia in murine allergic asthma

Abstract

Background

IL-37 is emerging as an anti-inflammatory cytokine, particularly in innate inflammation. However, the role of IL-37 in Th2-mediated allergic lung inflammation remains uncertain. We sought to determine the role and the underlying mechanisms of IL-37 in the development of house dust mites (HDM)-induced murine asthma model.

Methods

We examined the effect of IL-37 administration during the sensitization or challenge phase on Th2-mediated allergic asthma induced by inhaled HDM. Cellular source of CCL11 and distribution of IL-37 receptors, IL-18Rα and IL-1R8, were determined in HDM-exposed lungs. Finally, we examined the effect of IL-37 on CCL11 production and STAT6 activation in different primary lung structural cell types upon IL-4/IL-13 stimulation.

Results

IL-37 had no effect on HDM sensitization, but when administrated during the challenge phase, significantly attenuated pulmonary eosinophilia, CCL11 production and airway hyper-reactivity (AHR). Interestingly, IL-37 treatment had no significant effects on lung infiltrating T cells and Th2 cytokine production. Intranasal co-administration of CCL11 reversed the inhibiting effect of IL-37 on HDM-induced pulmonary eosinophilia and AHR. Furthermore, we demonstrated that CCL11 was primarily expressed by fibroblasts and airway smooth muscle cells (AMSC), while IL-37 receptors by tracheobronchial epithelial cells (TEC). In vitro study showed that IL-37 inhibited IL-4/IL-13–induced STAT6 activation and CCL11 production by fibroblasts and AMSC, which was dependent on its direct action on TEC. Moreover, cell-contact was required for the inhibitory effect of IL-37-treated TEC.

Conclusions

IL-37 attenuates HDM-induced asthma, possibly by inhibiting IL-4/IL-13-induced CCL11 production by fibroblasts and AMSC via its direct act on TEC.

http://ift.tt/2mmBL18

Usefulness of Asthma Predictive Index in Ascertaining Asthma Status of Children Using Medical Records: An Explorative Study

Abstract

Background

Frequent wheezing in original Asthma Predictive Index (API) was defined by parental report of recurrent wheezing within 1 year during the first 3 years of life. The nature of frequent wheezing in children, particularly aged over 3 years has not been studied. We aimed to assess the frequency and interval of wheezing to define frequent wheezing in ascertaining asthma for children using medical records.

Methods

Among children who participated in a previous study (n=427), all wheezing episodes documented in medical records were collected for children who had ≥2wheezing episodes PLUS met one major criteria or two minor criteria of API. We compared the distribution of known risk factors for asthma between subjects having two consecutive wheezing episodes with shorter interval (≤1year) compared to those with longer interval (1to3 years).

Results

62 children met API at median age of 2.3 years. During follow-up period (median age: 11.3 years), a total of 198 wheezing episodes were observed. 81% of wheezing intervals were within 3 years from the earlier wheezing episode, including 60% within 1 year. Children who met API based on 1 year interval (n=40) vs. 1to3 year interval (n=13) appeared to be similar in regard to the known risk factors for asthma.

Conclusions

Our exploratory study finding suggests that children who had frequent wheezing episodes with longer interval (<3 years) need to be considered to be determined as asthma cases when API is applied to retrospective medical records. Prospective studies with a larger sample size need to replicate this finding.

http://ift.tt/2qQFpEX

Immunoprofile of α-Gal- and B-antigen-specific responses differentiate red meat allergic patients from healthy individuals

Abstract

Background

The Galactose-α-1,3-galactose (α-Gal) epitope is involved in red meat allergy. As α-Gal is structurally similar to the blood group B antigen, we explored the relationship between the immune responses to α-Gal- and the B-antigen in red meat allergic patients compared to healthy A/O or B blood donors.

Methods

Sera from 51 red meat allergic patients IgE positive to α-Gal and 102 healthy blood donors (51 blood group A/O; 51 blood group B), were included. α-Gal and B-antigen specific IgE (ImmunoCAP) and IgG/IgG_1-4 (ELISA) responses were determined. Basophil activation tests were performed.

Results

Fifteen healthy donors were IgE positive to α-Gal, of which 3 had blood group B. The allergic patients had significantly higher α-Gal IgE levels compared to the healthy donors. The majority of the allergic patients, but none of the healthy donors, had IgE against the B-antigen. Inhibition studies revealed cross-reactivity between α-Gal and the B-antigen. The biological activity of the B-antigen was confirmed by basophil activation tests. Anti-α-Gal IgG₁ and IgG₄ levels were significantly higher in the patients compared to the healthy donors. Moreover, the IgG response to the B-antigen was comparable between the allergic patients and healthy A/O donors.

Conclusion

Red meat allergic patients showed significantly higher α-Gal IgE, IgG₁ and IgG₄ levels, reflecting a Th2 response, compared to healthy blood donors. Blood group B donors had significantly reduced antibody responses to α-Gal, due to similarities with the B-antigen, resulting in a lower risk of sensitization to α-Gal and development of red meat allergy.

http://ift.tt/2mqJ487

Epidemiology of atopic dermatitis in adults: results from an international survey

Abstract

Background

There are gaps in our knowledge of the prevalence of adult atopic dermatitis (AD).

Objective

To estimate prevalence of AD in adults and by disease severity.

Methods

This international, cross-sectional, web-based survey was performed in the United States, Canada, France, Germany, Italy, Spain, United Kingdom, and Japan. Adult members of online respondent panels were sent a questionnaire for AD identification and severity assessment; demographic quotas ensured population representativeness for each country. A diagnosis of AD required subjects to be positive on the modified UK Working Party/ISAAC criteria and self-report of ever having an AD diagnosis by a physician. The proportion of subjects with AD who reported being treated for their condition was determined and also used to estimate prevalence. Severity scales were Patient-Oriented SCORAD, Patient Oriented Eczema Measure, and Patient Global Assessment.

Results

Among participants by region, the point prevalence of adult AD in the overall/treated populations was 4.9%/3.9% in the US, 3.5%/2.6% in Canada, 4.4%/3.5% in EU, and 2.1%/1.5% in Japan. The prevalence was generally lower for males vs females, and decreased with age. Regional variability was observed within countries. Severity varied by scale and region; however, regardless of the scale or region, proportion of subjects reporting severe disease was lower than mild or moderate disease.

Conclusions

Prevalence of adult AD ranged from 2.1% to 4.9% across countries. Severe AD represented a small proportion of the overall AD population regardless of measure or region.

http://ift.tt/2qSkfXf

House dust mite impairs antiviral response in asthma exacerbation models through its effects on TLR3

Abstract

Background

Impaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections. Allergy is a known risk factor for viral-induced asthma exacerbation, but little is known whether allergens may affect interferon responses.

Objective

Our hypothesis is that house dust mite (HDM) impairs viral stimulus-induced antiviral signalling.

Methods

Experimental asthma exacerbations were produced in vitro in human bronchial epithelial cells (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C). We examined rhinovirus pattern recognition receptors (PRRs) signalling pathways and potential mechanisms of impaired interferon response.

Results

HBECs and mice exposed to HDM prior to Poly(I:C) exhibited a reduced antiviral response compared to Poly(I:C) alone, including reduced IFN-β, IFN-lambda, TLR3, RIG-I, MDA5, IRF-3 and IRF-7. Heat-inactivation of HDM partially restored the TLR3-induced interferon response in vitro and in vivo. Our HBEC-data further showed that HDM directly affects TLR3 signalling by targeting the receptor glycosylation level.

Conclusions

Direct effects of allergens such as HDM on PRRs can present as potential mechanism for defective antiviral airway responses. Accordingly, therapeutic measures targeting inhibitory effects of allergens on antiviral PRRs may find use as a strategy to boost antiviral response and ameliorate exacerbations in asthmatic patients.

http://ift.tt/2mnhfNK

Diagnostic accuracy, risk assessment, and cost-effectiveness of component-resolved diagnostics for food allergy: a systematic review

Abstract

Background

Component-resolved diagnostics (CRD) are promising tools for diagnosing food allergy, offering the potential to determine specific phenotypes and to develop patient-tailored risk profiles. Nevertheless, the diagnostic accuracy of these tests varies across studies; thus, their clinical utility remains unclear. Therefore, we synthesized the evidence from studies investigating the diagnostic accuracy, risk assessment ability, and cost-effectiveness of CRD for food allergy.

Methods

We systematically searched 10 electronic databases and four clinical trial registries for studies published January 2000-February 2017. The quality of included studies was assessed using QUADAS-2. Due to heterogeneity, we narratively synthesized the evidence.

Results

Eleven studies met inclusion criteria, altogether recruiting 1,098 participants. The food allergies investigated were cow's milk, hen's egg, peanut, hazelnut, and shrimp. The components with the highest diagnostic accuracy for each allergen, along with their sensitivity-specificity pairs, were: Bos d 4 for cow's milk (62.0% and 87.5%), Gal d 1 for hen's egg (84.2% and 89.8% for heated egg, and 60.6% and 97.1% for raw egg), Ara h 2 for peanut (80.3% and 95.1%), Cor a 14 for hazelnut (100% and 93.8%), and Lit v 1 for shrimp (82.8% and 56.3%) allergy.

Conclusion

Selected components of cow's milk, hen's egg, peanut, hazelnut, and shrimp allergen showed high specificity, but lower sensitivity. However, few studies exist for each component, and studies vary widely regarding the cut-off values used, making it challenging to synthesize findings across studies. Further research is needed to determine clinically appropriate cut-off values, risk assessment abilities, and cost-effectiveness of CRD approaches.

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The Safety and Effectiveness of a Novel Annular Keratopigmentation Method: A Case Report

Background: We investigated the safety and effectiveness of a novel aesthetic femtosecond-assisted annular keratopigmentation technique. Case Report: A 21-year-old female patient in good general and ophthalmological health with the wish to change the colour of her eyes was treated with a femtosecond-assisted annular keratopigmentation technique. Pigment was inserted in a channel in the cornea (external diameter 9.3 mm; internal diameter 5.5 mm) created with a femtosecond laser at a depth of 225 μm. Eight months post-operatively, there were no signs of leakage, diffusion, inflammation or any other detrimental effects on the cornea both objectively and subjectively. Conclusion: This procedure is a promising safe and effective option for those who want annular keratopigmentation for aesthetic reasons.
Case Rep Ophthalmol 2018;9:35–42

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Αρχειοθήκη ιστολογίου

Τετάρτη 10 Ιανουαρίου 2018

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