Analyses of dermal innate lymphoid cells in mice lacking T-bet and STAT6

Publication date: Available online 11 June 2018
Source:Allergology International
Author(s): Sohei Makita, Hiroaki Takatori, Tomohiro Tamachi, Akira Suto, Kotaro Suzuki, Hiroshi Nakajima




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Fellatio-associated erythema of the soft palate: an incidental finding during a routine dental evaluation

Oral lesions can have widely variable aetiology, hence, the importance of a comprehensive history and oral examination. We describe the case of a 47-year-old man who presented with an incidental erythematous lesion of the soft palate. The diagnosis was established during a routine dental examination. We found the lesion to be associated with the practice of fellatio. Oral sex is a very common sexual practice, and as clinicians we should consider it as a potential cause of palatal lesions in our differential diagnosis. This should also raise our suspicion for sexually transmitted diseases in high-risk patients.

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Recurrent meningitis caused by idiopathic cerebrospinal fluid rhinorrhoea from the sphenoid sinus

Description

A 41-year-old woman with 7 days of fever and headache had loss of consciousness 1 day prior to presentation. Despite the absence of trauma or other significant medical history, she had two episodes of meningitis in the previous 6 months. Physical examination showed no nuchal rigidity or abnormal findings on nasal endoscopy. Lumbar puncture showed a cerebrospinal fluid cell count of 750/μl. CT showed a bony defect of the posterior wall of the sphenoid sinus, which was filled with a soft tissue density. MRI showed fluid intensity in the same area (figure 1A, B). The diagnosis was recurrent meningitis due to possible idiopathic cerebrospinal fluid rhinorrhoea. Although a cisternogram is normally recommended, emergency drainage of the sphenoid sinus with antibiotic treatment was prioritised because of her deteriorating condition. With various possible diagnoses, an experienced surgeon operated on the patient. 

Figure 1

A bony defect of...

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Management of placenta percreta in a Jehovahs Witness patient

Placenta percreta is increasing in incidence and is associated with the risk of life-threatening haemorrhage. Patients who do not accept blood products present a unique challenge to obstetrician-gynaecologists. In this case report, we present the case of a 42-year-old pregnant Jehovah's Witness with a complete placenta previa and confirmed percreta at 26 weeks' gestation. Due to her religious beliefs against the use of blood products, she was managed with a stepwise surgical approach which involved caesarean delivery with internal iliac (hypogastric) artery ligation, weekly methotrexate and delayed hysterectomy 6 weeks later. Non-traditional, alternative approaches to the management of abnormal placentation in patients declining blood products warrant exploration.

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Persistent elevation of carcinoembryonic antigen as first presentation of a medullary thyroid carcinoma

Carcinoembryonic antigen (CEA) is still the most widely used tumour marker for gastrointestinal cancer. CEA was originally thought to be a specific marker for colorectal cancer, but it turned out to be a non-specific marker for further studies. CEA levels can be elevated in breast, lung and liver cancers, among others, including medullary thyroid cancer. The authors report a case of a 73-year-old woman who had a right hemicolectomy for an ascending colon adenocarcinoma and showed a persistent elevation in the CEA marker during follow-up. After several imaging tests, recurrence of the colon cancer was not found, but the presence of thyroid nodules had been detected. The diagnosis of a medullary thyroid carcinoma was made after the finding of a high value of calcitonin. The patient had a total thyroidectomy with resection of the central and lateral lymph nodes.

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Bronchogenic cyst infection presenting as pleuropericarditis

Description 

A 17-year-old woman was admitted to the emergency department with a 3-day history of dyspnoea (New York Heart Association Class II) and typical pleuritic pain following a 1-week history of cough and fever. Pneumonia was diagnosed based on a chest X-ray (figure 1A), and amoxicillin–clavulanate treatment was initiated. After 48 hours, the patient developed hypotension and tachycardia. Given hypotension, ongoing fever and rising C reactive protein despite antibiotic treatment, she was referred to the intensive care unit. On admission, an echocardiography was performed. A circumferential pericardial effusion with 14 mm maximum diameter adjacent to the right ventricle was detected, without haemodynamic compromise at the time. Besides, left pleural effusion was evidenced. An ultrasound-guided thoracentesis was conducted. Pleural fluid testing revealed the following findings: white blood cells (WBC) count 11.10⁹/Literwith 90% neutrophils, proteins 38 g/L, pH 7.36, glucose 6.3 mmol/L and lactate dehydrogenase (LDH) 492 IU/L. The culture exhibited no organism,...

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Septic arthritis of the temporomandibular joint leading to an epidural abscess

Septic arthritis of the temporomandibular joint (TMJ) is rare, but patients with this diagnosis are at high risk for significant morbidity. We present a case of a 15-year-old man who presented with increasing trismus for 3 days. He had only minimal discomfort and swelling of the right cheek and temporal region, and pericoronitis of an impacted wisdom tooth was suspected. Under intravenous antibiotics, pain subsided, but trismus and a slight swelling remained. CT scan showed septic arthritis of the TMJ with an abscess formation penetrating into the epidural space. Immediate drainage and craniotomy were performed. Under intravenous antibiotics, the patient made a full recovery. The source of infection remained undetermined. To our knowledge, this is the first reported case of septic arthritis of the TMJ spreading into the epidural space.

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Dentin dysplasia: diagnostic challenges

Dentin dysplasia(DD) is a rare autosomal dominant disorder associated with disturbance of the dentin. While the crowns appear clinically normal, on radiography, the pulp spaces appear partially or completely obliterated, with short blunted roots, and multiple periapical radiolucencies affecting the apparently sound teeth. Clinical signs include spontaneous abscess formation or increased tooth mobility which can lead to exfoliation. DD can therefore have a significant impact on the patient's dentition, and treatment is often challenging. Shields' classification of dentin disorders has been recently criticised for failing to consider differential variations and expressions of these disorders. This paper describes a case of a 23-year-old woman with previously undiagnosed DD, who presented with clinical and histological features belonging to several of these diseases, thus highlighting the potential diagnostic challenges faced with Shields' classification.

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Osteoporosis and malignancy: a dicey combination

Osteoporosis is the most common metabolic bone disorder worldwide, especially in women. Postmenopausal status is the most common risk factor for osteoporosis in elderly women. The operational diagnosis of osteoporosis is usually made with the help of central dual energy X-ray absorptiometry scan. Clinically, osteoporosis is suspected in the background of one or more fractures of the hip, vertebra, proximal humerus or pelvis in the absence of local disease or high-energy trauma. Serious underlying illness can present with vertebral fractures and can be missed if other clues from clinical examination and investigations are overlooked. We report a case emphasising this aspect.

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Primary carnitine deficiency in a 57-year-old patient with recurrent exertional rhabdomyolysis

Rhabdomyolysis is an emergency requiring rapid diagnosis and suitable aetiological treatment. We describe the case of a 57-year-old man with recurrent exertional rhabdomyolysis who was diagnosed with systemic primary carnitine deficiency (SPCD). Clinical examination was normal, creatine kinase levels were elevated, plasma free carnitine concentration was mildly decreased, muscle biopsy demonstrated lipid accumulation, carnitine uptake in cultured fibroblasts was decreased and genetic analysis identified a homozygous pathologic c.1181_1183del in the SLC22A5 gene. Rhabdomyolysis did not recur after treatment with oral L-carnitine was introduced. SPCD is a rare autosomal recessive disorder of carnitine transportation usually manifesting as an infantile (hepatic) or a childhood myopathic (cardiac) condition and rarely affecting adults. Our case indicates that SPCD should be considered in the aetiological evaluation of adult patients with recurrent exertional rhabdomyolysis, even in the absence of myopathy and cardiomyopathy.

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Horseshoe kidney with unilateral single ectopic ureter

The horseshoe kidney (HSK) is not an uncommon entity with an incidence of about 1 in 400 or 0.25% of the general population. It is also more commonly found in men as compared with women in a ratio of 2:1.An increased association of genitourinary anomalies have been found with HSK.Duplication of ureters occurs in 10% of HSKs. However, the association of HSK with single-system ectopic ureter is extremely rare. To our knowledge, no case with similar presentation has been reported in literature. Most cases of HSK with bilateral single ectopic ureters have been described. The aim of this report is to highlight the radiological and surgical findings in a case of HSK with unilateral single ectopic ureter.

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Traumatic corneal perforation with exteriorisation of Ahmed glaucoma valve tube

We report a rare case of traumatic corneal perforation with Ahmed glaucoma valve (AGV) tube. A 5-year-old female child, diagnosed with refractory glaucoma, had undergone AGV implantation, presented with the posterior migration of AGV tube after trauma to the eye. The detailed ocular history, ophthalmic findings, clinical course and surgical management are discussed.

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Metachronous renal Ewing sarcoma/primitive neuroectodermal tumour in a survivor of Burkitt lymphoma

We present a case of a 14-year-old girl who was diagnosed with Burkitt lymphoma in 2014. She was managed with chemotherapy and remained in remission for 3 years. On her surveillance imaging in 2017, a left-sided renal neoplastic mass was incidentally discovered. She underwent nephrectomy and pathology of the resected specimen revealed small cell tumour of the kidney with features favouring renal Ewing sarcoma/primitive neuroectodermal tumour. Molecular genetic analysis by fluorescence in situ hybridisation was performed which showed translocation of 22q12, thereby confirming the diagnosis. This is a rare secondary malignancy and an unusual association. This case highlights the importance and diagnostic dilemmas of rare secondary tumours in patients with such haematological malignancies and discusses its possible pathogenetic aspects.

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Thyroid Hormone Receptors Regulate the Expression of microRNAs with Key Roles in Skin Homeostasis

Thyroid, Ahead of Print.


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Leserbrief zu Ellies M. Aus der Gutachtenpraxis: Was ist eine Biopsie mit Inzision? Begutachtung der Kodierung im G-DRG-System in der HNO-Heilkunde. Laryngo-Rhino-Otol 2018; 97: 203–205

Laryngo-Rhino-Otol 2018; 97: 373-373
DOI: 10.1055/a-0612-9553

© Georg Thieme Verlag KG Stuttgart · New York

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Stapedotomie erfolgreich bei fortgeschrittener Otosklerose?

Laryngo-Rhino-Otol 2018; 97: 369-370
DOI: 10.1055/s-0044-100282

Heining et al. Audiological outcome of stapes surgery for far advanced cochlear otosklerosis. J Laryngol Otol 2017; 131: 961–964 Die cochleäre Otosklerose ist eine seltene Erkrankung des Innenohres, die zu einer Verknöcherung der Haarzellen führt und die Homöostase der Lymphströme negativ beeinflussen kann. Betroffene leiden unter Innenohrschwerhörigkeit, eine Therapie gilt als schwierig. Heining und Kolleginnen/Kollegen haben nun in einer retrospektiven Studie untersucht, ob Patienten mit fortgeschrittener Otosklerose von einer Stapedotomie profitieren können.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Fachsprache Medizin im Schnellkurs – Für Studium und Berufspraxis

Laryngo-Rhino-Otol 2018; 97: 376-376
DOI: 10.1055/a-0593-7276

© Georg Thieme Verlag KG Stuttgart · New York

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Spasmodische Dysphonie: Langzeitergebnisse mit Thyroplastik Typ 2

Laryngo-Rhino-Otol 2018; 97: 370-372
DOI: 10.1055/s-0043-121841

Sanuki T et al. Long-term Evaluation of Type 2 Thyroplasty with Titanium Bridges for Adductor Spasmodic Dysphonia. Otolaryngol Head Neck Surg 2017; 157: 80–84 Japanische Ärzte für Hals-, Nasen- und Ohrenheilkunde sowie Kopf- und Halschirurgie berichteten über stimmliche Langzeitergebnisse nach Durchführung einer Thyroplastik Typ 2 zur Behandlung der spasmodischen Dysphonie vom Adduktor Typ.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Antwort von Prof. Dr. med. Maik Ellies auf den Leserbrief von Jäckel M zu Ellies M. Aus der Gutachtenpraxis: Was ist eine Biopsie mit Inzision? Begutachtung der Kodierung im G-DRG-System in der HNO-Heilkunde. Laryngo-Rhino-Otol 2018; 97: 203–205

Laryngo-Rhino-Otol 2018; 97: 374-375
DOI: 10.1055/a-0612-9574

© Georg Thieme Verlag KG Stuttgart · New York

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Carcinoma in situ der Stimmlippe

Laryngo-Rhino-Otol 2018; 97: 377-378
DOI: 10.1055/a-0588-6611

© Georg Thieme Verlag KG Stuttgart · New York

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Wie würden Sie entscheiden?

Laryngo-Rhino-Otol 2018; 97: 415-418
DOI: 10.1055/a-0588-6633

© Georg Thieme Verlag KG Stuttgart · New York

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Das Plattenepithelkarzinom des Naseneingangs – Eine Literaturübersicht

Laryngo-Rhino-Otol 2018; 97: 379-391
DOI: 10.1055/a-0592-7965

Hintergrund Das Plattenepithelkarzinom des Naseneingangs (Vestibulum nasi) ist eine sehr seltene Tumorentität. In der Konsequenz herrscht bezüglich der Ätiologie, des Stagings und der notwendigen Therapie dieser Tumoren nach wie vor Uneinigkeit. Insbesondere die Mitbehandlung regionaler Lymphknotenstationen ist Gegenstand wissenschaftlicher Diskussionen. Methode Alle via Pubmed gefundenen Artikel zum Thema wurden hinsichtlich folgender Themenschwerpunkte untersucht: Lymphatische Versorgung, Metastasierung, Inzidenz, Prognose, Risikofaktoren (Leder, Nickel, Nikotin, Humane Papillomaviren), Tumorklassifikationssystem (UICC-, AJCC-, Wang-Klassifikation), Therapie des Primärtumors, Therapie regionaler Lymphknoten und Immunhistochemie. Ergebnisse Im vorliegenden Übersichtsartikel wurden 55 Veröffentlichungen ausgewertet. Die Ergebnisse hinsichtlich der untersuchten Aspekte sind in sich inhomogen. Schlussfolgerungen Als Klassifikationssystem wird die Wang-Klassifikation empfohlen. Für die Behandlung kleinerer Tumoren (T1-T2-Wang) kommen operative Resektionen oder Bestrahlungen in Betracht. Größere Tumoren (T3-Wang) sollten reseziert und einer adjuvanten Bestrahlung zugeführt werden. Im Falle einer cT1-cT2cN0-Situation kann – eine dezidierte bildgebende Diagnostik vorausgesetzt – auf eine elektive Therapie der regionalen Lymphknoten verzichtet werden.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Chirurgie bei Läsionen des Nervus facialis

Laryngo-Rhino-Otol 2018; 97: 419-434
DOI: 10.1055/a-0588-6622

Ursachen für eine Läsion mit nachfolgender Lähmung des N. facialis sind vielfältig, von der idiopathischen Fazialisparese bis hin zur Destruktion des Nervs durch einen malignen Tumor. Eine Indikation zur chirurgischen Intervention besteht immer dann, wenn die Wahrscheinlichkeit einer spontanen Heilung mit gutem funktionellen Ergebnis gering oder gar nicht vorhanden ist, und eine medikamentöse Behandlung nicht möglich oder auch der chirurgischen Therapie unterlegen ist.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Fragen für die Facharztprüfung

Laryngo-Rhino-Otol 2018; 97: 435-436
DOI: 10.1055/a-0588-6664

© Georg Thieme Verlag KG Stuttgart · New York

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Rhinoplastik

Laryngo-Rhino-Otol 2018; 97: 437-440
DOI: 10.1055/a-0588-6708

© Georg Thieme Verlag KG Stuttgart · New York

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Kommentar der Schriftleitung

Laryngo-Rhino-Otol 2018; 97: 367-368
DOI: 10.1055/a-0588-6578

© Georg Thieme Verlag KG Stuttgart · New York

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Population Pharmacokinetics and Safety of Solithromycin Following Intravenous and Oral Administration in Infants, Children, and Adolescents [PublishAheadOfPrint]

Solithromycin is a novel fluoroketolide antibiotic, which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age 6 years [range 4 days - 17 years]) were administered intravenous (IV) or oral (capsules or suspension) solithromycin (IV 6-8 mg/kg; capsules/suspension 14-16 mg/kg on Day 1 and 7-15 mg/kg on Days 2-5). PK samples were collected after first and multi-dose administration. Data from 83 subjects (662 samples) were combined with previously collected adolescent PK data (N=13, median [range] age 16 years (12-17)) following capsule administration to perform a population PK analysis. A 2-compartment PK model characterized the data well, and post-menstrual age was the only significant covariate after accounting for body size differences. Dosing simulations suggested that 8 mg/kg IV daily and oral dosing of 20 mg/kg on Day 1 (800 mg adult maximum) followed by 10 mg/kg on Days 2-5 (400 mg adult maximum) would achieve pediatric solithromycin exposure consistent with exposures observed in adults. Seventy-six treatment-emergent adverse events (TEAEs) were reported in 40 subjects. Diarrhea (6 subjects) and infusion site pain or phlebitis (3 subjects) were the most frequently reported adverse events related to treatment. Two subjects experienced TEAEs of increased hepatic enzymes that were deemed not to be related to study treatment.

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"Emergence of azole resistant Aspergillus fumigatus from immunocompromised hosts in India" [PublishAheadOfPrint]

This prospective study shows that the rate of azole resistant Aspergillus fumigatus (ARAF) in Indian immunocompromised patient population with invasive aspergillosis (IA) is low, 6/706 (0.8%). This lower rate supports the continued use of voriconazole as the first line of treatment. However, the ARAF in this study exhibited three kinds of unreported cyp51A mutations from India, of which two were at hot spots, G54R and P216L while one was at codon Y431C.

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In vitro and in vivo Evaluation of APX001A/APX001 and other Gwt1 inhibitors against Cryptococcus [PublishAheadOfPrint]

Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. Here we evaluated the in vitro and in vivo activity of several compounds including APX001A and its prodrug APX001, currently in clinical development for invasive fungal infections. These compounds target the conserved Gwt1 enzyme that is required for the localization of glycosylphosphatidyl inositol (GPI)-anchored cell wall mannoproteins in fungi.

The Gwt1 inhibitors had low MIC values, ranging from 0.004 μg/mL to 0.5 μg/mL against both C. neoformans and C. gattii. APX001A and APX2020 demonstrated in vitro synergy with fluconazole (FICI 0.37). In a CM model, APX001 and fluconazole each, alone, reduced log₁₀ colony forming units (CFU)/g brain (0.78 and 1.04, respectively), whereas the combination resulted in a reduction of 3.52 log₁₀ CFU/g brain.

Efficacy as measured by a reduction in brain and lung fungal burden was also observed for another Gwt1 inhibitor prodrug, APX2096, where dose dependent reductions in fungal burden ranged between 5.91 and 1.79 log₁₀ CFU/g lung and between 7.00 and 0.92 log₁₀ CFU/g brain, representing near or complete sterilization of lung and brain tissue at the higher doses. These data support further clinical evaluation of this new class of antifungal agents for CM.

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In Vitro activity of ceftazidime-avibactam against carbapenem-resistant and hypervirulent Klebsiella pneumoniae isolates [PublishAheadOfPrint]

Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains have emerged while antimicrobial treatment options remain limited. Herein, we tested the in vitro activity of ceftazidime-avibactam and other comparator antibiotics against 65 CR-hvKp isolates. Ceftazidime-avibactam, colistin and tigecycline are highly active in vitro against CR-hvKp isolates (MIC90 ≤ 1μg/ml), including KPC-2-producing ST11 CR-hvKp. Based upon previous clinical experience and the in vitro data presented herein, we posit that ceftazidime-avibactam is a considered therapeutic option against CR-hvKp infections.

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Potency of solithromycin against fast and slow growing chlamydial organisms [PublishAheadOfPrint]

Evidence is provided that solithromycin is a bactericidal against not only fast growing chlamydial organisms but also those slowed by IFN in vitro. At sub-lethal concentrations, Sol impedes homotypic fusion of Chlamydia-containing vacuoles and reduces secretion of the type III secretion (T3S) effector, IncA. Sol may therefore represent a potential new clinical treatment for Chlamydia infections. Selective perturbation of the T3S system suggests a novel mode of antibacterial action for Sol that warrants further investigation.

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Colistin does not potentiate ceftazidime-avibactam killing of carbapenem-resistant Enterobacteriaceae in vitro or suppress emergence of ceftazidime-avibactam resistance [PublishAheadOfPrint]

We tested ceftazidime-avibactam and colistin against 24 carbapenem-resistant Enterobacteriaceae (CRE) by time-kills. Ceftazidime-avibactam (0.25x, 1x, 4x MIC) was bactericidal against 8%, 21%, and 88% of isolates, respectively. Colistin (2μg/mL) was bactericidal against 83% (12 hours) and 42% (24 hours) of isolates. In combination, synergy and antagonism was identified against 13% and 46% of isolates, respectively. The combination did not suppress ceftazidime-avibactam resistance. Colistin plus ceftazidime-avibactam did not provide benefit over ceftazidime-avibactam against most CRE isolates.

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Phase I Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants (PROOF) [PublishAheadOfPrint]

The pharmacokinetics (PK), safety, and tolerability of two repeated dosing regimens of oral fosfomycin tromethamine were evaluated in 18 healthy adult subjects. Subjects received 3 g every other day (QOD) for 3 doses then every day (QD) for 7 doses, or vice versa, in a phase I, randomized, open-label, two-period crossover study. Serial blood (n=11) and urine samples (n=4 collection intervals) were collected before and up to 24 hours after dosing on Days 1 and 5 along with pre-dose concentrations on Days 3 and 7. PK parameters were similar between Days 1 and 5 within and between dosing regimens. The mean (±SD) PK parameters of fosfomycin in plasma on Day 5 during the QOD and QD dosing regimens, respectively, were: C_max= 24.4±6.2 vs 23.8±5.6 μg/mL, T_max= 2.2±0.7 vs. 2.0±0.4 h, V_d/F= 141±67.9 vs. 147±67.6 liters, CL/F= 21.4±8.0 vs. 20.4±5.3 liters/h, CL_R= 7.5±4.1 vs. 7.3±3.5 liters/h, AUC_0-24= 151.6±35.6 vs. 156.6±42.5 μg⋅h/mL, and t_1/2= 4.5±1.1 vs. 5.0±1.7 h. Urine concentrations peaked at approximately 600 μg/mL through the 0-8 hours urine collection intervals but displayed significant interindividual variability. Roughly 35-40% of the 3 g dose was excreted in the urine by 24 hours post-dose. No new safety concerns were identified during this study. The proportion of diarrhea-free days during the study was significantly lower in the QD regimen compared to the QOD regimen (61% vs. 77%, P<0.0001). Further studies establishing the clinical benefit:risk ratio of repeated dosing regimens of oral fosfomycin tromethamine are warranted.

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Tet38 Efflux Pump Contributes to Fosfomycin Resistance in Staphylococcus aureus [PublishAheadOfPrint]

Fosfomycin inhibits MurA following uptake by the GlpT transporter of glycerol-3-phosphate in Escherichia coli. In Staphylococcus aureus, plasmid overexpression of the Tet38 efflux pump and a glpT mutant resulted in increased MICs and decreased accumulation of fosfomycin, with MICs affected by glycerol-3-phosphate. In contrast, a tet38 mutant had a lower MIC and increased accumulation of fosfomycin, suggesting that Tet38 acts as an efflux transporter of fosfomycin.

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Biochemical and Structural Basis of Triclosan Resistance in a Novel Enoyl-Acyl Carrier Protein Reductase [PublishAheadOfPrint]

Enoyl-acyl carrier protein reductase (ENR), such as FabI, FabL, FabK and FabV, catalyzes the last reduction step in bacterial type II fatty acid biosynthesis. Previously, we reported metagenome-derived ENR homologs resistant to triclosan (TCL) and highly similar to 7-α hydroxysteroid dehydrogenase (7-AHSDH). These homologs are commonly found in Epsilonproteobacteria, a class that contains several human pathogenic bacteria, including the genera Helicobacter and Campylobacter. Herein, we report the biochemical and predicted structural basis of TCL resistance in a novel 7-AHSDH-like ENR. The purified protein exhibited NADPH-dependent ENR activity but no 7-AHSDH activity, despite its high homology with 7-AHSDH (69%-96%). Because this ENR was similar to FabL (41%), we propose that this metagenome-derived ENR is referred to as FabL2. Homology modeling, molecular docking, and molecular dynamic simulation analyses revealed the presence of an extrapolated six-amino acid loop specific to FabL2 ENR, which prevented the entry of TCL into the active site of FabL2 and was likely responsible for TCL resistance. Elimination of this extrapolated loop via site-directed mutagenesis resulted in the complete loss of TCL resistance but not enzyme activity. Phylogenetic analysis suggested that FabL, FabL2, and 7-AHSDH diverged from a common short-chain dehydrogenase reductase family. This study is the first to report the role of the extrapolated loop of FabL2-type ENRs in conferring TCL resistance. Thus, the FabL2 ENR represents a new drug target specific for pathogenic bacteria of Epsilonproteobacteria.

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Cis- and trans-acting factors influence expression of the norM-encoded efflux pump of Neisseria gonorrhoeae and levels of gonococcal susceptibility to substrate antimicrobials [PublishAheadOfPrint]

The gonococcal NorM efflux pump exports substrates with a cationic moiety including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. The norM gene is part of a four gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (Ts) between the -10 and -35 hexamers; the majority of gonococcal strains analyzed herein contained a T-6 sequence. Primer extension analysis showed that regardless of the length of the poly-T tract, the same transcriptional start site (TSS) was used for expression of norM. Interestingly, the T-6 tract correlated with a higher level of both norM expression and gonococcal resistance to NorM substrates BE and EB. Analysis of expression of genes downstream of norM showed that the product of the tetR-like gene has the capacity to activate expression of norM as well as murB, which encodes an acetylenolpyroylglucosamine reductase predicted to be involved in the early steps of peptidoglycan synthesis. Moreover, loss of the TetR-like transcriptional regulator modestly increased gonococcal susceptibility to NorM substrates EB and BE. We conclude that both cis- and trans-acting regulatory systems can regulate expression of the norM operon and influence levels of gonococcal susceptibility to antimicrobials exported by NorM.

https://ift.tt/2HHaKNE

Clonal background, resistance gene profile, and porin gene mutations modulate in vitro susceptibility to imipenem/relebactam in diverse Enterobacteriaceae [PublishAheadOfPrint]

Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While Klebsiella pneumoniae harboring bla_KPC account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether CRE species and antibiotic resistance genotype influence response to relebactam (REL), a novel beta-lactamase inhibitor with class A/C activity, combined with imipenem(IMI)/cilastatin. We carried out broth microdilution testing to IMI alone or in the presence of 4 μg/mL REL in 154 clinical isolates collected at a New York City hospital with high prevalence of bla_KPC including Enterobacter spp. (n=96), K. pneumoniae (n=44), Escherichia coli (n=1), Serratia marcescens (n=9) and Citrobacter spp. (n=4). Resistance gene profiles and presence of major porin gene disruptions were ascertained by whole genome sequencing. Addition of REL decreased the IMI MIC to the susceptible range (≤1 μg/mL) in 88% of isolates. However, S. marcescens IMI/REL MICs were 4 to 8-fold higher than those of other organisms. Most bla_KPC-positive isolates had IMI/REL MICs ≤1 μg/mL (88%), including E. cloacae ST171 (93%) and K. pneumoniae ST258 (82%). Nineteen isolates had IMI/REL MICs ≥2 μg/mL, of which 84% harbored bla_KPC and one was bla_NDM-1-positive. Isolates with IMI/REL MICs ≥2 μg/mL versus ≤1 μg/mL were significantly more likely to demonstrate disruption of at least one porin gene (42% versus 19%, p=0.04), although most S. marcescens isolates (67%) had intact porin genes. In conclusion, while REL reduced IMI MICs in a majority of diverse CRE isolates including high-risk clones, chromosomal factors impacted IMI/REL susceptibilities and may contribute to elevated MICs in S. marcescens.

https://ift.tt/2sNxmri

Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses [PublishAheadOfPrint]

Morbidity and mortality resulting from influenza-like disease are a threat especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics are urgently needed that are efficacious against major drivers of influenza-like disease including influenza viruses and respiratory syncytial virus (RSV). Using a dual-pathogen high throughput screening protocol for influenza A virus (IAV) and RSV inhibitors, we have identified N⁴-hydroxycytidine (NHC) as a potent inhibitor of RSV, influenza B viruses and IAVs of human, avian, and swine origin. Biochemical in vitro polymerase assays and viral RNA sequencing revealed that the ribonucleotide analog is incorporated into nascent viral RNAs in place of cytidine, increasing the frequency of viral mutagenesis. Viral passaging in cell culture in the presence of inhibitor did not induce robust resistance. Pharmacokinetic profiling demonstrated dose-dependent oral bioavailability of 36-56%, sustained levels of the active 5'-triphosphate anabolite in primary human airway cells and mouse lung tissue, and good tolerability after extended dosing at 800 mg/kg/day. The compound was orally efficacious against RSV and both seasonal and highly pathogenic avian IAV in mouse models, reducing lung virus loads and alleviating disease biomarkers. Oral dosing reduced IAV burden in a guinea pig transmission model and suppressed virus spread to uninfected contact animals through direct transmission. Based on its broad-spectrum efficacy and pharmacokinetic properties, NHC a promising candidate for future clinical development as a treatment option for influenza-like diseases.

https://ift.tt/2HGwLft

Multiple drug resistant Acinetobacter baumannii chloramphenicol resistance requires an inner membrane permease [PublishAheadOfPrint]

Acinetobacter baumannii is a Gram negative organism that is a cause of hospital acquired multidrug resistant (MDR) infections. A. baumannii has a unique cell surface compared to many other Gram-negative pathogens in that it can live without LPS and it has a high content of cardiolipin in the outer membrane. Therefore, to better understand the cell envelope and mechanisms of A. baumannii MDR, we screened a transposon library for mutants with defective permeability barrier function, as defined as a deficiency in the ability to exclude the phosphatase chromogenic substrate, 5-Bromo-4-chloro-3-indolyl phosphate (XP). We identified multiple mutants in the gene ABUW_0982, predicted to encode a permease broadly present in A. baumannii isolates, with increased susceptibility to the ribosome targeting antibiotic chloramphenicol (CHL). Moreover, when compared to other known CHL resistance genes such as chloramphenicol acyl-transferases, we find ABUW_0982 is the primary determinant of intrinsic CHL resistance in A. baumannii strain 5075, an important isolate responsible for severe MDR infections in humans. Finally, studies measuring the efflux of chloramphenicol and expression of ABUW_0982 in CHL-susceptible E. coli support the conclusion that ABUW_0982 encodes a single-component efflux protein with specificity for small, hydrophobic molecules, including CHL.

https://ift.tt/2JwMFyU

The Prevalence of a Cefazolin Inoculum Effect Associated with blaZ Gene Types Among Methicillin-Susceptible Staphylococcus aureus Isolates from Four Major Medical Centers in Chicago [PublishAheadOfPrint]

Cefazolin efficacy with high inoculum methicillin-susceptible Staphylococcus aureus (MSSA) infections remains in question due to therapeutic failure inferred from an inoculum effect. This study investigated the local prevalence of a cefazolin inoculum effect (CInE) and its association with staphylococcal blaZ gene types among MSSA isolates in the Chicago area. Four medical centers in Chicago, Illinois contributed MSSA isolates. Cefazolin MICs (C-MIC) were determined at 24 hours by broth microdilution method using standard inocula (SI, 5 x 10⁵ CFU/mL) and high inocula (HI, 5 x 10⁷ CFU/mL). The CInE was defined as 1) a ≥ 4-fold increase in C-MIC between SI and HI and/or 2) a pronounced CInE: a nonsusceptible C-MIC of ≥ 16 μg/mL at HI. PCR was used to amplify the blaZ gene, followed by agarose gel electrophoresis and sequencing to determine the gene type. Approximately 269 MSSA isolates were included. All but one isolate was susceptible to cefazolin at SI and 97% remained susceptible at HI. A total of 196 isolates (73%) were blaZ-positive, led by gene type C (40%). The CInE was seen in 45 blaZ-positive isolates (23%) with 44 (22%) presenting a ≥ 4-fold increase in C-MIC (SI to HI) and five (3%) with a pronounced CInE. Four out of the five, met both definitions of CInE with two expressing the type A gene. The prevalence of a pronounced CInE associated with the type A blaZ gene from MSSA isolates in Chicago is low. Our predilection for cefazolin use, even early in the management of hospitalized MSSA infections, is tenable.

https://ift.tt/2HDoAAF

Identification of 14 alpha-lanosterol demethylase (CYP51) in Scedosporium species [PublishAheadOfPrint]

Scedosporium spp. cause infections (scedosporiosis) in both immunocompetent and immunocompromised individuals and may persistently colonise the respiratory tract in patients with cystic fibrosis (CF). They are less susceptible against azoles when compared with other moulds such as Aspergillus, suggesting the presence of resistance mechanisms. It can be hypothesised that the decreased susceptibility of Scedosporium spp. to azoles is also CYP51 dependant. Analysis of the S. apiospermum and S. aurantiacum genome revealed one CYP51 gene encoding the 14 alpha-lanosterol demethylase. This gene of 159 clinical or environmental Scedosporium and three Lomentospora prolificans isolates has been sequenced and analysed. The Scedosporium CYP51 protein clustered with the group of known CYP51B orthologues and showed species-specific polymorphisms. A tandem repeat in the 5' upstream region of Scedosporium CYP51 like that in A. fumigatus could not be detected. Species-specific amino acid (aa) alterations in CYP51 of S. boydii, S. ellipsoideum, S. dehoogii and S. minutisporum isolates were located on positions that have not been described as having an impact on azole susceptibility. In contrast, two of the three S. apiospermum-specific aa changes (Y136F and G464S) corresponded to respective mutations in A. fumigatus CYP51A at aa position 121 and 448 (Y121F and G448S) that had been linked to azole resistance.

https://ift.tt/2Jvv4HE

Molecular confirmation of the linkage between Rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance. [PublishAheadOfPrint]

Rhizopus oryzae is the most prevalent causative agent of Mucormycosis, an increasingly reported opportunistic fungal infection. These mucormycetes are intrinsically resistant to Candida- and Aspergillus-active antifungal azole drugs such as fluconazole and voriconazole, respectively. Despite of its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work is to establish if the Rhizopus oryzae CYP51 genes are the unique responsible for voriconazole and fluconazole intrinsic resistance in these fungal pathogens. Two CYP51 genes were identified in R. oryzae genome. We classify them as CYP51A and CYP51B based on their sequence similarity with other known fungal CYP51 genes. Later, we obtained a chimerical Aspegillus fumigatus strain harboring a functional R. oryzae CYP51A gene expressed under the regulation of wild type A. fumigatus CYP51A promoter and terminator. The mutant was selected after transformation by using a novel procedure taking advantage of the FLC-hypersusceptibility of the used A. fumigatus CYP51A deletant mutant as recipient strain. The A. fumigatus transformants harboring the R. oryzae CYP51A mimicked exactly the azole susceptibility patterns of this Mucormycete. The data presented in this work demonstrate that R. oryzae CYP51A coding sequence is the unique responsible of the R. oryzae azole susceptibility patterns.

https://ift.tt/2LKxizB

Risk factors for gastrointestinal colonization and acquisition of carbapenem-resistant Gram-negative bacteria among patients in intensive care units in Thailand [PublishAheadOfPrint]

This study was conducted to investigate the prevalence and risk factors for carbapenem-resistant Gram-negative Bacteria (CR-GNB) colonization and acquisition among patients admitted to Intensive Care Units (ICUs) in two tertiary care hospitals in Northern Thailand. Rectal swab screening for CR-GNB was performed on patients at ICU admission and discharge. Phenotypes and genotypes of all isolates were determined. Risk factors were analyzed by logistic regression analysis. Overall, carriage rates of CR-GNB at admission was 11.6% (32/275), mostly with Acinetobacter baumannii (n = 15) followed by Klebsiella pneumoniae (n = 9). The risk factor for CR-GNB colonization was hospitalization within the previous 6 months (P = 0.002). During ICU stay, the rate of CR-GNB acquisition was 25.2% (52/206), predominantly A. baumannii (n = 28) and K. pneumoniae (n = 13). Risk factors associated with CR-GNB acquisition were the use of enteral feeding tube (P = 0.008) and administration of third generation cephalosporins (P = 0.032) and carbapenems (P = 0.045). The most common carbapenemase genes in A. baumannii and K. pneumoniae were bla_OXA-23/51 and bla_NDM, respectively. Patient-to-patient transmission was demonstrated in three cases resulting in the acquisition of CR-A. baumannii spp. (2 cases) and K. pneumoniae (1 case) isolates from other patients who were admitted during the same period of time. This is the first Indochinese study screening patients and examining carriage of CR-GNB, and further demonstrating transfer of CR-GNB isolates in ICUs. Our study suggested that effective infection control measures are required to limit the spread of CR-GNB within the hospitals.

https://ift.tt/2sNQJQG

The effect of the novel antifungal drug F901318 (Olorofim) on the growth and viability of Aspergillus fumigatus [PublishAheadOfPrint]

F901318 (olorofim) is a novel antifungal drug that is highly active against Aspergillus species. Belonging to a new class of antifungals called the orotomides, F901318 targets dihydroorotate dehydrogenase (DHODH) in the de novo pyrimidine biosynthesis pathway. In this study, the antifungal effects of F901318 against Aspergillus fumigatus were investigated. Live-cell imaging revealed that, at a concentration of 0.1 μg/ml, F901318 completely inhibited germination, but conidia continued to expand by isotropic growth for >120 h. When this low F901318 concentration was applied to germlings or vegetative hyphae their elongation was completely inhibited within 10 h. Staining with the fluorescent viability dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC) showed that prolonged exposure to F901318 (>24 h) led to vegetative hyphal swelling and a decrease in hyphal viability through cell lysis. The time-dependent killing of F901318 was further confirmed by measuring fungal biomass and growth rate in liquid culture. Compared to the untreated control, the ability of hyphal growth to recover in drug-free medium after 24h exposure to F901318 was strongly impaired. A longer treatment of 48h further improved the antifungal effect of F901318. Together, the results of this study indicate that F901318 initially has a fungistatic effect on Aspergillus spp. isolates by inhibiting germination and growth, but prolonged exposure is fungicidal through hyphal swelling followed by cell lysis.

https://ift.tt/2LKx6An

Severe Renal Impairment Has Minimal Impact on Doravirine Pharmacokinetics [PublishAheadOfPrint]

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor in development for use with other antiretroviral therapies to treat human immunodeficiency virus 1 (HIV-1) infection. Doravirine metabolism predominantly occurs via cytochrome P450 3A with <10% of elimination occurring via the renal pathway. As severe renal impairment can alter the pharmacokinetics (PK) of metabolically eliminated drugs, the effect of severe renal impairment on doravirine PK was assessed.

A single dose of doravirine 100 mg was administered to subjects aged 18–75 years with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m² (severe renal impairment group) and healthy controls with an eGFR of ≥80 mL/min/1.73 m², matched to the mean of the renal impairment group by age (±10 years) and weight (±10 kg). Doravirine plasma concentrations were determined at regular intervals and safety was monitored throughout.

The geometric mean ratios (90% confidence interval) for severe renal impairment/healthy subjects were 1.43 (1.00, 2.04), 1.38 (0.99, 1.92), and 0.83 (0.61, 1.15) for plasma doravirine area under the curve from zero to infinity (AUC_0–), plasma concentration at 24 hours post-dose (C₂₄), and maximum plasma concentration (C_max), respectively. Doravirine was generally well tolerated in both groups.

Based on the overall efficacy, safety, and PK profile of doravirine, the minor effect of severe renal impairment on doravirine PK observed in this study is not considered clinically meaningful.

https://ift.tt/2JyuCIN

Erratum: Periphere Regionalanästhesie ohne Komplikationen – Ein Traum wird wahr?!

Anästhesiol Intensivmed Notfallmed Schmerzther
DOI: 10.1055/a-0629-0254

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2MiqeLC

Low drug survival of apremilast for psoriasis in a real-word-setting

https://ift.tt/2HJIzhe

Systematic Review of the Therapeutic Roles of Adipose Tissue in Dermatology

Adipose tissue is rich in stem cells that secrete trophic factors; Several studies have demonstrated improved outcomes in scarring, wound healing, and hair growth with adipose tissue treatments; The evidence on using adipose tissue to treat complex dermatologic conditions is not strong enough to justify changes to current clinical practice.

https://ift.tt/2sQ4Nt5

Epidemiology of Staphylococcal Scalded Skin Syndrome in United States Adults

https://ift.tt/2HExBJR

Review: Surgical Smoke: Risks Assessment and Mitigation Strategies

Dermatologists are repeatedly exposed to surgical smoke from lasers and electrosurgery.; There are relevant infectious, direct physical, chemical, and mutagenic risks of surgical smoke.; These risks can be minimized by use of respirator masks and smoke evacuation systems.

https://ift.tt/2JsVutv

12-hydroxyeicosatetraenoic acid (12-HETE) levels are increased in Actinic Keratoses (AK) and Squamous Cell Carcinoma (SCC)

https://ift.tt/2HFEf2x

Hypoglossal nerve stimulator generator migration: INSPIRE device reimplantation with parallels to cardiac implantable electronic devices

Implantation rates of hypoglossal nerve stimulators, such as INSPIRE, are increasing. The device is still in its early stages of complication reporting, which to date includes implant related infection requiring device removal, and stimulation lead cuff dislodgement requiring replacement. Here we present a 48-year-old female who experienced generator migration and stimulator lead tension requiring an additional operation in order to resecure the generator device. This proved unsuccessful and a second surgery was performed with complete relocation of the device generator to inhibit device migration.

https://ift.tt/2JsVGZC

Effect of artemisinin and neurectomy of pterygoid canal in ovalbumin-induced allergic rhinitis mouse model

Allergic rhinitis (AR), characterized by sneezing, nasal itching and rhinorrhea, affects a large number of population. This study aimed to explore the effects of artemisinin alone or combined with neurectomy o...

https://ift.tt/2y3kYrZ

Cytomegalovirus reactivation in a critically ill patient: a case report

The aim of this case report is to discuss diagnostic workup and clinical management of cytomegalovirus reactivation in a critically ill immunocompetent pediatric patient.

https://ift.tt/2sNUqWK

Is fine needle aspiration biopsy reliable in the diagnosis of parotid tumors? Comparison of preoperative and postoperative results and the factors affecting accuracy

Publication date: Available online 11 June 2018
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Fazilet Altin, Yalcin Alimoglu, Resit Murat Acikalin, Husamettin Yasar
IntroductionFine needle aspiration biopsy is a valuable tool in preoperative evaluation of head and neck tumors. However, its accuracy in management of salivary gland tumors is debatable.ObjectiveWe aimed to investigate the efficacy and the accuracy of fine needle aspiration biopsy in parotid gland tumors.MethodsPatients who underwent parotidectomy between January 2008 and June 2017 due to parotid gland tumor were examined retrospectively. Patients with both preoperative fine needle aspiration biopsy and postoperative surgical pathologies were included. Preoperative fine needle aspiration biopsy was categorized as benign, malignant or suspicious for malignancy. Surgical pathology was grouped as benign or malignant. Surgical pathology was compared with fine needle aspiration biopsy, and sensitivity, specificity, accuracy and agreement between both tests were investigated.Results217 cases were evaluated and 23 cases were excluded because the fine needle aspiration biopsy diagnosis was non-diagnostic or unavailable. 194 cases were included. The mean age of the patients was 47.5±15.88 (7–82). There were 157 benign, 37 malignant cases in fine needle aspiration biopsy, 165 benign and 29 malignant cases in surgical pathology. The most common benign tumor was pleomorphic adenoma (43.3%), and malignant tumor was mucoepidermoid carcinoma (4.13%). The diagnostic accuracy for fine needle aspiration biopsy when detecting malignancy was 86.52%. Sensitivity and specificity were 68.96% and 89.63% respectively. Positive predictive value was 54.05% and negative predictive value was 94.23%. There was moderate agreement between fine needle aspiration biopsy and surgical pathology (κ=0.52). The sensitivity was 54.54% in tumors less than 2cm while 77.77% in larger tumors. In tumors extending to the deep lobe, sensitivity was 80%.ConclusionFine needle aspiration biopsy is an important diagnostic tool in evaluation of parotid gland tumors. It is more accurate in detecting benign tumors. In tumors greater than 2cm and extending to the deep lobe, the sensitivity of fine needle aspiration biopsy is high. The use of fine needle aspiration biopsy in conjunction with clinical and radiological evaluation may help to reduce false positive and false negative results.



https://ift.tt/2xYT1Sh

A morphological classification for vocal fold leukoplakia

Publication date: Available online 11 June 2018
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Min Chen, Changjiang Li, Yue Yang, Lei Cheng, Haitao Wu
IntroductionThere is still no general method for discriminating between benign and malignant leukoplakia and identifying vocal fold leukoplakia.ObjectiveTo evaluate the reliability of a morphological classification and the correlation between morphological types and pathological grades of vocal fold leukoplakia.MethodsA total of 375 patients with vocal fold leukoplakia between 2009 and 2015 were retrospectively reviewed. Two observers divided the vocal fold leukoplakia into flat and smooth, elevated and smooth, and rough type on the basis of morphological appearance. The inter-observer reliability was evaluated and the results of classification from both observers were compared with final pathological grades. Clinical characteristics between low risk and high risk group were also analyzed.ResultsThe percentage inter-observer agreement of the morphological classification was 78.7% (κ=0.615, p<0.001). In the results from both observers, the morphological types were significantly correlated with the pathological grades (p1<0.001, p2<0.001, Kruskal–Wallis test; r1=0.646, p1<0.001, r2=0.539, p2<0.001, Spearman Correlation Analysis). Multivariate analysis showed patient's age (p=0.018), the size of lesion (p<0.001), and morphological type (p<0.001) were significantly different between low risk group and high risk group. Combined receiver operating characteristic curve analysis of significant parameters revealed an area under the receiver operating characteristic curve of 0.863 (95% CI 0.823–0.903, p<0.001).ConclusionsThe proposed morphological classification of vocal fold leukoplakia was consistent between observers and morphological types correlated with pathological grades. Patient's age, the size of lesion, and morphological type might enable risk stratification and provide treatment guidelines for vocal fold leukoplakia.



https://ift.tt/2MjxpD5

Cervical paragangliomas: experience of 114 cases in 14 years

Publication date: Available online 11 June 2018
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Halil Basel, Nazim Bozan
Introduction and objectiveTo report a single center experience with carotid body paraganglioma cases that were treated by the same surgeon in a city with high prevalence of paragangliomas due to high altitude.MethodsWe retrospectively investigated the demographic, clinicopathological and radiological data of 104 patients diagnosed with cervical paragangliomas between 2003 and 2017. The patients were classified according to the Shamblin classification.ResultsIn this study a total of 104 patients (33 male and 71 female, with a mean age of 54.6±13 years) diagnosed with cervical paragangliomas located on carotid bifurcation between 2003 and 2017 were included. Among those patients, 10 presented with bilateral tumors and in total, 114 paragangliomas were managed in this period. The mean diameter of the tumors was 5.12±1.45cm. Malignant tumor was determined in only one (0.9%) patient. All patients were operated. In 12 patients with the tumor diameter larger than 5cm, preoperative coil embolization was achieved. In 14 patients, preoperative angiographic embolization was employed and in 4 patients intraoperative sclerosing agent injections were performed. Facial paralysis was observed in 2 patients and dysphagia was present in 1 patient, Horner syndrome was seen in 1 patient and hoarseness was reported in 7 patients after operation. All those complications improved during follow-up. Mortality was not reported in any cases.ConclusionSurgery is the definitive treatment for patients with cervical paragangliomas. Although, it may be difficult in patients with the advanced Shamblin types, in experienced hands, complication rates are very low.



https://ift.tt/2Mfn5fk

Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey

Publication date: Available online 11 June 2018
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Eduardo Madruga Lombardo, Fábio Luiz Dal Moro Maito, Cláiton Heitz
IntroductionSolitary plasmacytoma is a rare malignant tumor of plasma cells with no evidence of systemic proliferation. There are two known subtypes: extramedullary solitary plasmacytoma and solitary bone plasmacytoma. The etiology is still unknown. Both lesions present a risk of progression to multiple myeloma. A number of approaches have been used for treatment of solitary plasmacytoma.ObjectiveTo carry out a systematic review of the case reports described in the literature, focusing on therapeutic and prognostic aspects.MethodsA search of clinical case reports was performed in the PubMed database using Mesh Terms related to "plasmacytoma" under the following criteria: type of study (case report), articles in English language, conducted in humans, with no publication date limits.ResultsOf the 216 articles found, only 21 articles met the pre-established inclusion criteria.ConclusionThe occurrence of solitary bone plasmacytoma in the bones of the face is a rare condition prevalent between the 4th and 6th decades of life, located in the posterior region of the mandible in most cases. Histopathological examination and systemic investigation are mandatory for confirmation of diagnosis.



https://ift.tt/2JDKuW6

Grant Funds Collaborative Project to Find New Treatments for Liver Cancer

Researchers with the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins University School of Medicine received a $3 million grant to use computational modeling and software to understand biological data, in combination with unique in vitro and animal studies, to better treat liver cancer.

https://ift.tt/2l45H0U

Study of ISU104, Targeting ERBB3 in Patients With Advanced Solid Tumors

Condition:   Solid Tumor
Intervention:   Biological: ISU104
Sponsor:   ISU Abxis Co., Ltd.
Recruiting

https://ift.tt/2JJwHRa

Effects of Probiotics in Preventing Oral Mucositis

Condition:   Head-and-neck Cancer
Interventions:   Drug: Lactobacillus Reuteri Oral Solution [BioGaia];   Drug: Placebos
Sponsor:   National University Hospital, Singapore
Not yet recruiting

https://ift.tt/2y7Eq6S

Study to Evaluate the Safety, Tolerate, Pharmacokinetics and Preliminary Efficacy of CYH33

Conditions:   Advanced Solid Tumors;   Advanced Esophagus Cancer and Squamous Cell Carcinoma of the Esophageal Junction
Intervention:   Drug: CYH33 for tablet
Sponsor:   ShangHai HaiHe Pharmaceutical
Recruiting

https://ift.tt/2MgsO4F

Gastrointestinal CMV Disease and Tuberculosis in an AIDS Patient: Synergistic Interaction between Opportunistic Coinfections

The AIDS pandemic has made diseases such as tuberculosis, CMV disease, and other opportunistic infections more prevalent; these diseases may even be found to be associated among themselves, and the natural history of each disease may present in an unusual manner. We report the case of a 41-year-old man with HIV (CD4 of 144 cells/dL) and HCV with hematochezia due to tuberculosis in the ileocecal valve and descending colon and CMV tissue invasive disease in the esophagus and descending colon. Coinfection among tuberculosis and cytomegalovirus in the gastrointestinal tract was described only once in a patient with a recent diagnosis of HIV that affected the distal ileum and ascending colon. We will discuss the peculiarities of the case and the behavior of the immune system in the face of simultaneous opportunistic infections. This is a challenging scenario that has scarce publications and is of great clinical importance.

https://ift.tt/2JEePEg

Burkitt’s lymphoma presenting as acute appendicitis: a case report

Abstract

Appendiceal lymphomas are exceedingly rare, constituting around 0.015% of all gastrointestinal lymphoma cases. Burkitt's lymphoma is the second most prevalent pathology, diagnosed in 25.9% of patients. We report a case of a 36-year-old male admitted with acute abdominal pain with 2 days of evolution, localized in the right lower quadrant associated with hyporexia, but no fever. On examination he presented abdominal tenderness on the right iliac fossa. A diagnosis of acute appendicitis was made clinically. At the post-operative follow up, 2 weeks later, he presented a low back pain of high intensity, associated with swelling of the abdomen, night sweats, daily fevers and weight loss. The histopathological exam of the appendix revealed diffuse and transmural lymphoid proliferation. Immunohistochemistry suggested high grade B-cell lymphoma indicative of Burkitt's lymphoma. This patient was staged as a IVxB lymphoma and was submitted into polychemotherapy with a complete clinical response in 8 months.

https://ift.tt/2Jrl565

Cecal ameboma mimicking obstructing colonic carcinoma

Abstract

Ameboma is a mass of granulation tissue with peripheral fibrosis and a core of inflammation related to amebic chronic infection. The initial presentations of colonic ameboma usually include obstruction and low gastrointestinal bleeding. It may mimic colon carcinoma or other granulomatous inflammatory conditions of the colon in both the clinical presentation and the endoscopic appearance. Here, we report a case of a 45-year-old male with a presentation of abdominal pain and constipation, as well as clinical, radiological and endoscopic presentation resembling colonic carcinoma, that was managed operatively with right hemicolectomy and post-operative histopathologic finding of cecal ameboma.

https://ift.tt/2HBVemc

Irreversible electroporation in borderline resectable pancreatic adenocarcinoma for margin accentuation

Abstract

Achieving clear microscopic resection margins following pancreaticoduodenectomy (PD) is challenging particularly in borderline resectable pancreatic carcinoma (BRPC). Positive resection margins has been identified as a major independent prognostic factor. Irreversible electroporation (IRE) has emerged as a promising non-thermal ablative method that could be used in the treatment of pancreatic cancer as an adjunct to chemotherapy and surgery. This case report describes the successful simultaneous intraoperative IRE and PD in a patient with BRPC, achieving clear microscopic resection margins. Technical aspects and histology showing the effect of IRE are presented. The role of IRE in the treatment of pancreatic adenocarcinoma should be further evaluated in prospective studies.

https://ift.tt/2Jsk8dI

Spontaneous adrenal hemorrhage. Report of two cases and review of pathogenesis, diagnosis and management

Abstract

Adrenal hemorrhage represents a relatively rare condition, usually associated with meningococcal septicemia. It is an underestimated cause of acute decompensation, multiorgan failure and death, usually diagnosed post-mortem. Depending on its etiology adrenal hemorrhage is categorized as traumatic and non-traumatic. The technical advancement of imaging modalities, has made diagnosis and management more efficient. Assessment of hemodynamic stability, exclusion of a hormonal active adrenal tumor and assessment for adrenal insuffi¬ciency, are of cardinal importance. Angiographic embolization has contributed significantly in better outcomes as emergency laparotomy is associated with high morbidity and mortality rates. Hereby we present two cases of spontaneous adrenal hemorrhage associated with extensive retroperitoneal bleeding and hemodynamic instability. Both underwent angiography with one requiring embolization with favorable outcome. Investigation for exclusion of underlying adrenal tumor, adrenal insufficiency and follow-up imaging are presented in detail for both cases.

https://ift.tt/2HBVaCY

A Rare Presentation of Clozapine-Induced DRESS Syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) is an uncommon side effect of certain medications. It causes a skin reaction, with eosinophilia and other organ involvement. This case describes a presentation of a 32-year-old female with a past medical history significant for schizophrenia and bipolar disorder who presented for a rash. She had been started on clozapine 10 days prior to admission. After extensive workup she was found to have DRESS syndrome secondary to clozapine use. This is the second reported case in the literature of clozapine-induced DRESS syndrome. This case is unique because it is the first case to present with the common manifestations of DRESS syndrome including eosinophilia, rash, lymphadenopathy, and organ involvement after clozapine use.

https://ift.tt/2JA0pos

Odontogenic Cutaneous Fistula: A Cause of Persistent Cervical Discharge

Odontogenic cutaneous fistulas often lead to intense levels of patient discomfort and suffering. Due to its rarity and the absence of dental symptoms, a considerable number of patients are usually misdiagnosed which results in inappropriate management. This case report presents a 16-year-old patient with a 2-year history of a nonhealing, persistently discharging lesion in the left submandibular region of the neck. The patient underwent exploration of the left submandibular region, and a fistulous tract directed superomedially to the ipsilateral lower molar teeth was excised. A subsequent panoramic orthopantomogram performed one week postoperatively demonstrated radiolucency is the distal root of tooth 37. A final diagnosis of odontogenic cutaneous fistula was made, and the patient was referred to the Maxillofacial Department for treatment of the offending tooth.

https://ift.tt/2xZ1KDX