Head and Neck Diseases by Alexandros G.Sfakianakis: 10/30/18

Τρίτη 30 Οκτωβρίου 2018

Comparative Evaluation of Immunohistochemical Expression of p16 with p16 Microsatellite Marker by PCR in Surgical Margins of Oral Squamous Cell Carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is most common oral cancer with multifactorial etiology. Surgical therapy is treatment of choice but known to have recurrence. The main reason for recurrence is associated with surgical margins which need to be tumor free. Changes at genetic level cannot be ascertained only through routine light microscopy in surgical margins, even though they are tumor free. Detection of early marker like p16 can help in predicting the risk of recurrence. Hence study aimed to detect p16 microsatellite marker (D9s1747) in surgical margins of oral squamous cell carcinoma and compare the same with p16 marker through immunohistochemistry. Total of 40 paraffin embedded tissue samples diagnosed and surgically treated cases of OSCC were included. From each sample one tumor proper and one surgical margin was obtained. From paraffin embedded tissue sample 2 sections of 4 µm thick was obtained from tumor proper and tumor margin. One section was stained with hematoxylin and eosin and other section was stained immunohistochemically using p16 antibody. DNA extraction was done for tumor proper and surgical margin tissue and PCR analysis was carried for p16 microsatellite marker (D91747). Out of 40 cases 37 cases showed positivity in tumor proper for p16 with IHC. Out of 37 cases 23 cases showed positivity for both tumor proper and surgical margin. There were 3 cases negative for tumor proper. Out of these 3 cases, 1 (33.3%) case was positive for surgical margin. Out of 40 cases 27 cases showed positivity for tumor proper with p16 microsatellite marker. Out of 27 cases 16 cases showed positivity for both tumor proper and surgical margin. There were 13 cases negative for tumor proper. However there were 8 (61.5%) cases negative which were in tumor proper but showed positivity for surgical margin. Other 5 cases were negative in both tumor proper and surgical margin. Our study reveals that surgical margins of OSCC exhibit alteration in p16 markers both by IHC and PCR techniques. p16 and p16 microsatellite marker detection in margins indicates field change. Further studies with larger sample size comparing expression with clinical and histological parameter and follow up has to be done to substantiate our findings.

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Prurigo pigmentosa – Response to treatment with Q‐Switched neodymium: YAG at 532 nm

Australasian Journal of Dermatology, EarlyView.

https://ift.tt/2Ju874i

Scalp BCC's and meningioma following X‐ray epilation for tinea capitis

Australasian Journal of Dermatology, EarlyView.

https://ift.tt/2DbHXCY

Prurigo pigmentosa – Response to treatment with Q‐Switched neodymium: YAG at 532 nm

Australasian Journal of Dermatology, EarlyView.

https://ift.tt/2Ju874i

Scalp BCC's and meningioma following X‐ray epilation for tinea capitis

Australasian Journal of Dermatology, EarlyView.

https://ift.tt/2DbHXCY

Comparative Evaluation of Immunohistochemical Expression of p16 with p16 Microsatellite Marker by PCR in Surgical Margins of Oral Squamous Cell Carcinoma

Abstract

https://ift.tt/2qjMRWb

Ileal schwannoma causing intussusception in an adult

Ileal schwannomas are extremely rare tumours. Very few cases have been previously reported. Most cases present with abdominal pain and gastrointestinal bleeding; intussusception is a rare presentation. Due to limitations in imaging modalities, arriving at a diagnosis preoperatively can be challenging. The only reliable method of diagnosis, and treatment, is resection of the tumour, followed by histological and immunohistochemical testing. This report details the rare case of intussusception as the presenting feature of an ileal schwannoma.

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Infected and obstructed kidney secondary to sloughed necrotic renal papilla

Description

A 66-year-old Afro-Caribbean woman presented with a 1-day history of sharp left flank pain. This was associated with nausea and diarrhoea, without fever or urinary symptoms. Her medical history includes type 2 diabetes mellitus on insulin therapy but with suboptimal control (haemoglobin A1c 80 mmol/mol or 0.23 g/dL glucose levels) and related complications including chronic kidney disease, retinopathy, peripheral neuropathy, hypertension, sickle cell trait, obesity and osteoarthritis. Blood investigations demonstrated leucocytosis (white cell count 12.7x10⁹/L) and deranged renal function (creatinine 150 µmol/L; baseline 110 µmol/L). Urine dipstick test was positive for nitrites, ketones and glucose and urine culture isolated mixed growth of bacteria with Candida.

A CT abdomen/pelvis, initially planned on the working diagnosis of acute diverticulitis, revealed a mild left-sided hydroureteronephrosis associated with perinephric inflammatory stranding. Left posterolateral bladder wall thickening and left distal ureteric enhancement were also highlighted (figures 1 and 2). The patient was...

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Salmonella Enteritidis breast abscess: an unusual cause of breast abscess in the UK

Breast abscess is a common clinical condition mostly caused by Staphylococcus aureus. However, infections due to mixed organisms are observed in non-lactational women, mostly in smokers. Salmonella infection causing breast abscess is extremely rare in developed countries. We report a case of Salmonella enterica subsp enterica (I) serovar Enteritidis breast abscess in a 48-year-old woman, a UK citizen, who had recently travelled abroad. She was treated successfully with a combination of surgery and ciprofloxacin. Unusual causative organisms should be kept in mind in patients with recent travel abroad and pus should be sent for microbiology. Mastitis caused by Salmonella spp can present with a severely indurated area that may take a few weeks to resolve. Complete assessment with biopsy of the indurated area and breast imaging is mandatory to exclude malignancy.

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Linezolid-associated serotonin toxicity after escitalopram discontinuation: concomitant drug considerations

We report a case of a hospitalised patient who developed probable serotonin toxicity shortly after the initiation of linezolid in whom the selective serotonin reuptake inhibitor (SSRI) escitalopram had been recently discontinued. On day 2 of linezolid administration, the patient reported severe anxiety and was observed to have full body jerking and twitching motions without mental status change. Notably, the patient was concomitantly receiving the antidepressant, trazodone and the benzodiazepine, clonazepam possibly affecting the severity and manifestations of serotonin toxicity. Linezolid was discontinued after 5 days and the patient's symptoms resolved. Serotonin toxicity can present with an array of symptoms and be life threatening if left unrecognised. This report highlights the clinical lessons that discontinuation of an SSRI upon initiation of linezolid does not eliminate the risk of serotonin toxicity and that other concomitant medications may worsen or improve some of the symptoms lending delay and uncertainty to the diagnosis.

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Neurocysticercosis: a reversible and rare cause of seizure in the developed world

Description

A 22-year-old man, originally from India, presented to an emergency department in Canada with a new-onset seizure and collapse associated with a few seconds of right eye and tongue deviation. This event occurred following 6 weeks of difficulty concentrating and unilateral left-sided headache. On examination, no focal neurological deficits were found. A non-contrast CT head was requested which showed a left-sided occipital lesion. A follow-up brain MRI revealed the 'hole-with-dot' lesion pathognomonic for neurocysticercosis (NCC).

NCC is caused by the tapeworm Taenia solium and is the most common parasitic infection of the central nervous system, endemic to many low-income countries worldwide. T. solium is transmitted among humans via the faecal–oral route, with pigs acting as an intermediate host. Humans are a definitive host for the intestinal tapeworm which produces eggs containing an infective embryo (oncosphere). This embryo can actively cross the intestinal wall into the blood stream and deposit in...

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Adjacent schwannomas originating from intercostal and sympathetic nerves

Description

Schwannomas are the most frequent type of intrathoracic neurogenic tumour, but the presence of multiple simultaneous schwannomas is a rare occurrence. We experienced a patient initially thought to have a single schwannoma based on preoperative imaging, but who was subsequently found to have two adjacent schwannomas arising from different nerves.

A 48-year-old woman showed an abnormal shadow on chest X-ray during a medical examination. CT-guided biopsy did not provide a definitive diagnosis, and she was therefore referred to our department. Her general condition was good and her neurological findings were normal. No skin pigmentation or subcutaneous nodules were observed. Chest CT revealed a 5.5 cm segmental lobular tumour in the right posterior mediastinum (figure 1A) and chest MRI showed that the tumour continued from the right intervertebral foramina (figure 1B). We suspected schwannoma of the intercostal nerve, and performed video-assisted thoracoscopic surgery in the...

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A Global MicroRNA Profile in Fanconi Anemia: A Pilot Study

Metabolic Syndrome and Related Disorders, Ahead of Print.

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Large Cytologically Benign Thyroid Nodules Do Not Have High Rates of Malignancy or False-Negative Rates and Clinical Observation Should be Considered: A Meta-Analysis

Thyroid, Ahead of Print.

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Iodine Content of the Best-Selling United States Adult and Prenatal Multivitamin Preparations

Thyroid, Ahead of Print.

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Evaluation of folded amniotic membrane and injectable amniotic membrane pieces as soft tissue filler materials

The search for safe and effective tissue fillers has been an ongoing effort for many years. Obtaining biological materials from patients can require additional incisions and brings surgical and cosmetic risks as a major disadvantage. The aim of this experimental study was, therefore, to evaluate the efficacy of folded amniotic membrane as a soft tissue filler and to assess its volume, and to investigate the possible usage of injectable amniotic membrane for augmentation.

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Migraine increases the proportion of sudden sensorineural hearing loss: A longitudinal follow-up study

The aim of the present study was to investigate the proportion of sudden sensorineural hearing loss (SSNHL) patients in a representative population cohort with migraine.

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Torsion Does Not Affect Early Vein Graft Patency in the Rat Femoral Artery Model

J reconstr Microsurg
DOI: 10.1055/s-0038-1675224

Background Torsion of vein grafts is a commonly cited reason for graft failure in clinical setting. Many microsurgery training courses have incorporated vein graft procedures in their curricula, and vein graft torsion is a common technical error made by the surgeons in these courses. To improve our understanding of the clinical reproducibility of practicing vein graft procedures in microsurgery training courses, this study aims to determine if torsion can lead to early vein graft failure in nonsurvival surgery rat models. Methods Sprague-Dawley rats were divided into five cohorts with five rats per cohort for a total of 25 rats. Cohorts were labeled based on degree of vein graft torsion (0, 45, 90, 135, and 180 degrees). Torsion was created in the vein grafts at the distal arterial end by mismatching sutures placed between the proximal end of the vein graft and the distal arterial end. Vein graft patency was then verified 2 and 24 hours postoperation. Results All vein grafts were patent 2 and 24 hours postoperation. At 2 hours, the average blood flow rate measurements for 0, 45, 90, 135, and 180 degrees of torsion were 0.37 ± 0.02, 0.38 ± 0.04, 0.34 ± 0.01, 0.33 ± 0.01, and 0.29 ± 0.02 mL/min, respectively. At 24 hours, they were 0.94 ± 0.07, 1.03 ± 0.15, 1.26 ± 0.22, 1.41 ± 0.11, and 0.89 ± 0.15 mL/min, respectively. Conclusion Torsion of up to 180 degrees does not affect early vein graft patency in rat models. To improve the clinical reproducibility of practicing vein graft procedures in rat models, we suggest that microsurgery instructors assess vein graft torsion prior to clamp release, as vessel torsion does not seem to affect graft patency once the clamps are removed.
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Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents | Abstract | Full text

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Interaction Between Pitch and Timbre Perception in Normal-Hearing Listeners and Cochlear Implant Users

Abstract

Despite their mutually exclusive definitions, pitch and timbre perception interact with each other in normal-hearing (NH) listeners. Cochlear implant (CI) users have worse than normal pitch and timbre perception. However, the pitch-timbre interaction with CIs is not well understood. This study tested the interaction between pitch and sharpness (an aspect of timbre) perception related to the fundamental frequency (F0) and spectral slope of harmonic complex tones, respectively, in both NH listeners and CI users. In experiment 1, the F0 (and spectral slope) difference limens (DLs) were measured with a fixed spectral slope (and F0) and 20-dB amplitude roving. Then, the F0 and spectral slope were varied congruently or incongruently by the same multiple of individual DLs to assess the pitch and sharpness ranking sensitivity. Both NH and CI subjects had significantly higher pitch and sharpness ranking sensitivity with congruent than with incongruent F0 and spectral slope variations, and showed a similar symmetric interaction between pitch and timbre perception. In experiment 2, CI users' melodic contour identification (MCI) was tested in three spectral slope (no, congruent, and incongruent spectral slope variations by the same multiple of individual DLs as the F0 variations) and two amplitude conditions (0- and 20-dB amplitude roving). When there was no amplitude roving, the MCI scores were significantly higher with congruent than with no, and in turn than with incongruent spectral slope variations. The 20-dB amplitude roving significantly reduced the overall MCI scores and the effect of spectral slope variations. These results reflected a confusion between higher (or lower) pitch and sharper (or duller) timbre and offered important implications for understanding and enhancing pitch and timbre perception with CIs.

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Game Changer: Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis

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Game Changer: Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis

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Game Changer: Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis

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Game Changer: Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD)

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Interaction Between Pitch and Timbre Perception in Normal-Hearing Listeners and Cochlear Implant Users

Abstract

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Prognostic role of BAP-1 and PBRM-1 expression in intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (ICC) has universally poor outcome, mainly due to its late clinical presentation. Identification of specific biomarkers and development of effective treatment are still urgently required. Mutations in PBRM-1 and BAP-1 genes, and the expression of S100P have been related to survival in ICC. miR-31 seems also to play important regulatory functions in ICC and it directly regulates BAP-1 expression in lung cancer. In this study, tissue expression of BAP-1, PBRM-1, S100P, and miR-31 was investigated in ICC and correlated with clinical-pathological features. Sixty-one consecutive patients who underwent curative hepatic resection for ICC were enrolled. None received any therapy prior to surgery. Immunostaining for BAP-1, PBRM-1, and S100P, and in situ hybridization for miR-31 were performed, using tissue microarray slides. A strong retained expression of BAP-1 and PBRM-1 was associated with a reduced overall (p = 0.04 and p = 0.002, respectively) and disease-free survival (p = 0.05 and p = 0.02, respectively). An overexpression of S100P was related to a reduced overall survival (p = 0.005). The multivariate analyses identified the presence of perineural invasion and the retained PBRM-1 expression as independent predictors of worse overall [p = 0.02, hazard ratio (HR) = 2.25 (1.16–4.39) and p = 0.001, HR = 3.13 (1.56–6.28), respectively] and disease-free survivals [p = 0.03, HR = 2.43 (1.09–5.4) and p = 0.03, HR = 2.51 (1.11–5.67), respectively]. An overexpression of S100P was predictive of a worse overall survival [p = 0.02, HR = 1.66 (1.08–2.55)]. High levels of miR-31 were significantly associated to a low expression of BAP-1 protein (p = 0.03). In ICC, a retained expression of BAP-1 and PBRM-1, and an overexpression of S100P are related to a poor prognosis.

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Association between intraoperative phenylephrine administration and umbilical artery pH in women with hypertensive disorders of pregnancy: a retrospective cohort study

Abstract

Purpose

In healthy pregnant women undergoing Cesarean section, treatment of post-spinal hypotension (PSH) with phenylephrine is reportedly more efficacious than ephedrine in preventing a decline in umbilical artery pH (UApH), which is an indicator of fetal acidosis. However, phenylephrine has the potential to reduce placental blood flow and consequently decrease UApH in women who develop hypertensive disorders of pregnancy (HDP), due to decreased cardiac function and placental vascular abnormalities. We aimed to verify the association between decreased UApH and phenylephrine administered before delivery to treat PSH in women with HDP.

Methods

This single-center retrospective cohort study was conducted between April 2008 and October 2016 by assessing the records of pregnant women with confirmed or suspected HDP who underwent Cesarean section under spinal anesthesia. The association between phenylephrine and the primary endpoint of decreased UApH was investigated using logistic regression analysis and propensity score matching.

Results

In the original cohort of 107 pregnant women with HDP, neither univariate nor multivariate analysis indicated a significant association between phenylephrine treatment and decreased UApH [crude odds ratio (OR) = 2.26; 95% confidence interval (CI) 0.75–6.77; P = 0.14], (adjusted OR = 1.80; 95% CI 0.55–5.93; P = 0.33). Thirty patients each who were not treated with phenylephrine (control group) and were treated with phenylephrine (phenylephrine group) were matched by propensity score analysis. UApH [median (interquartile range)] was not significantly different between control and phenylephrine groups [7.30 (7.25–7.35) vs. 7.27 (7.25–7.30); P = 0.14].

Conclusion

Intraoperative phenylephrine administration to treat PSH in women with HDP was not associated with decreased UApH.

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Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes

Abstract

Purpose

In this study, we aimed to describe the real-life practice outcomes of pertuzumab–trastuzumab–taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients.

Methods

This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers.

Results

Median age was 51 (22–82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5–40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure.

Conclusions

Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab–trastuzumab–taxane therapy to date.

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Is low dose radiotherapy an effective treatment for Baker’s cyst?

Abstract

Purpose

Osteoarthritis of the knee is a common disease, often associated with a Baker's cyst. Besides osteoarthritis, also other joint pathologies of the knee can be causative for a Baker's cyst. Radiotherapy is known to be an effective treatment for osteoarthritis, with an anti-inflammatory effect. As the excessive production of synovia usually is associated with intraarticular inflammation, our hypothesis was that radiotherapy might positively influence the synovial production and reduce the volume of a Baker's cyst.

Materials and methods

We performed a prospective trial, including 20 knees receiving radiotherapy for knee arthritis. Besides documentation of NRS (numeric rating scale), WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and Knee Society Score, the volume of the Baker's cyst was calculated for a short- (6 to 12 weeks) and long-term (9 to 12 months) follow-up. Ultrasonic volumetry was performed using an ultrasound device with a high-resolution multifrequency linear probe (6–9 MHz).

Results

Low-dose radiotherapy improved NRS, WOMAC score and Knee Society Score significantly. The mean volume of Baker's cyst decreased from 22.3 ml to 10.7 respectively 3.1 ml during follow-up. A decrease in volume of more than 25% compared to the baseline could be achieved for 75% of the patients in the short-term and 79% of the patients in the long-term follow up.

Conclusion

Radiotherapy of knee osteoarthritis is an effective treatment that decreases the volume of a Baker's cyst. Most patients respond to the treatment. Whether radiotherapy is an effective treatment for Baker's cyst without associated osteoarthritis has to be further examined.

https://ift.tt/2SwVlGo

Combination of serum squamous cell carcinoma antigens 1 and 2 as potential diagnostic marker for sinonasal squamous cell carcinoma and inverted papilloma

Head &Neck, EarlyView.

https://ift.tt/2PuoK59

Radiculomegaly of canines in oculofaciocardiodental syndrome

Abstract

Oculofaciocardiodental (OFCD) syndrome is a rare genetic disease, first reported by Hayward in 1980. This syndrome presents with various ocular, facial, cardiac, and dental symptoms, including congenital cataract, dysmorphic facial features, congenital heart disease, and enlarged roots, respectively. The most important criteria for the diagnosis of OFCD syndrome are dental abnormalities, especially extreme elongation of canine roots. Here, we report detailed analysis of the dentofacial region, as well as ocular, facial, cardiac, and dental findings in a female with OFCD syndrome. To the best of our knowledge, the patient in this case is the first such patient reported in South Korea.

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Lipome péri-unguéal : une localisation inhabituelle

Publication date: Available online 30 October 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): S. Gallouj, N. Aqil, F. Zahra Mernissi

Résumé

Introduction

Les lipomes sont des tumeurs mésenchymateuses bénignes courantes composées de cellules graisseuses matures qui peuvent être ou non entourées d'une fine capsule fibreuse. Les lipomes impliquant les doigts sont extrêmement rares mais doivent être pris en compte dans le diagnostic différentiel des masses bénignes des tissus mous de localisation digitale. Nous décrivons un cas de lipome péri-unguéal.

Observation

Une femme de 65 ans se présentait en consultation avec une tuméfaction de l'index droit évoquant un lipome. Elle ne se plaignait d'aucune douleur mais avait une légère limitation des mouvements du doigt affecté. Les diagnostics différentiels qu'on pouvait envisager étaient un neurofibrome, un fibromyxome acral superficiel et une tumeur à cellules géantes des gaines synoviales des tendons. Une excision chirurgicale était effectuée. L'examen histologique confirmait le diagnostic de lipome. Il n'y avait pas d'antécédent de traumatisme de l'ongle, d'autres lipomes sur le corps ni d'antécédents familiaux de lipomatose. Il n'y a pas eu de récidive après une année de suivi.

Discussion

Les lipomes des doigts sont extrêmement rares. À notre connaissance, six cas de localisation sous-unguéale et quatre cas situés dans le bord latéral de l'ongle ont été décrits dans la littérature. Nous rapportons un autre cas de localisation inhabituelle, péri-unguéale postérieure. Des examens radiologiques peuvent être réalisés pour aider au diagnostic. Bien que les lipomes des doigts soient des entités rares, ils doivent être pris en compte dans le diagnostic différentiel des masses bénignes des tissus mous du doigt.

Summary

Background

Lipomas are common benign mesenchymal tumors composed of mature fat cells that may or may not be surrounded by a thin fibrous capsule. Lipomas involving the fingers are extremely rare but must be taken into account in the differential diagnosis of benign soft tissue masses of unusual localization. We describe a case of digital periungual lipoma.

Patients and methods

A 65-year-old Moroccan woman presented with a tumefaction of the right index finger reminiscent of a lipoma. There was no history of nail trauma, other lipomas on the body, or a family history of lipomatosis. She did not complain of any pain, but she had a slight limitation on the movement of the affected finger. Surgical excision was performed. Histological examination confirmed the diagnosis of lipoma. There was no recurrence after one year of follow-up.

Discussion

Lipomas of the fingers are extremely rare. To our knowledge, 6 cases of subungual localization and 4 cases in the lateral edge of the nail have been described in the literature. We report another case of unusual posterior periungual localization. In our case, the suspected diagnoses were either neurofibroma, superficial acral fibromyxoma, or giant cell tumor of the synovial sheaths of the tendons. Radiological examinations may be performed to aid diagnosis. Although finger lipomas are rare entities, they must be considered in the differential diagnosis of benign soft tissue masses of the finger.

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Cell-free DNA in cancer: current insights

Abstract

Background

The field of liquid biopsies in oncology is rapidly expanding, with the application of cell-free circulating tumour DNA (ctDNA) showing promise in this era of precision medicine. Compared with traditional clinical and radiographic tumour monitoring methods, the analysis of ctDNA provides a minimally-invasive and technically feasible approach to assess temporal and spatial molecular evolutions of the tumour landscape. The constantly advancing technological platforms available for ctDNA extraction and analysis allow greater analytical sensitivities than ever before. The potential translational impact of ctDNA as a blood-based biomarker for the identification, characterization and monitoring of cancer has been demonstrated in numerous proof-of-concept studies, with ctDNA analysis beginning to be applied clinically across multiple facets of oncology.

Conclusions

In this review we discuss the biology, recent advancements, technical considerations and clinical implications of ctDNA in the context of cancer, and highlight important challenges and future directions for the integration of ctDNA into standardised patient care.

https://ift.tt/2q98WXs

Molecular features unique to glioblastoma radiation resistant residual cells may affect patient outcome - a short report

Abstract

Purpose

Previously we have shown, using a primary glioblastoma (GBM) cell model, that a subpopulation of innately radiation resistant (RR) GBM cells survive radiotherapy and form multinucleated and giant cells (MNGCs) by homotypic fusions. We also showed that MNGCs may cause relapse. Here, we set out to explore whether molecular characteristics of RR cells captured from patient-derived primary GBM cultures bear clinical relevance.

Methods

Primary cultures were derived from 19 naive GBM tumor samples. RR cells generated from these cultures were characterized using various cell biological assays. We also collected clinicopathological data of the 19 patients and assessed associations with RR variables using Spearman's correlation test and with patient survival using Kaplan-Meier analysis. Significance was determined using a log-rank test.

Results

We found that SF2 (surviving fraction 2) values (p = 0.029), days of RR cell formation (p = 0.019) and percentage of giant cells (p = 0.034) in the RR population independently correlated with a poor patient survival. We also found that low ATM (Ataxia-telangiectasia mutated) expression levels in RR cells showed a significant (p = 0.002) negative correlation with SF2 values. A low ATM expression level in RR cells along with a high tumor volume was also found to negatively correlate with patient survival (p = 0.011). Finally, we found that the ATM expression levels in RR cells independently correlated with a poor patient survival (p = 0.014).

Conclusions

Our data indicate that molecular features of innately radiation resistant GBM cells independently correlate with clinical outcome. Our study also highlights the relevance of using patient-derived primary GBM cultures for the characterization of RR cells that are otherwise inaccessible for analysis.

https://ift.tt/2yAcpTn

Long non-coding RNAs as monitoring tools and therapeutic targets in breast cancer

Abstract

Background

Current therapeutic strategies that are used to combat breast cancer vary widely and largely depend on its clinicopathological features, including tumor subtype, size, stage, lymph node involvement, the presence of hormone receptors and/or HER2, as well as the degree of proliferative activity. Recent work has focused on improving our knowledge on the molecular mechanisms that underlie this complex disease. Most of the human genome is transcribed into RNAs that do not encode proteins. These noncoding RNAs may act as mediators in the regulation of gene expression. Based on their size and function, noncoding RNAs are classified into small noncoding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs). LncRNAs have been found to play key roles in relevant biological processes, including breast cancer. As such, lncRNAs have been proposed as diagnostic and prognostic biomarkers, as predictive biomarkers and as putative therapeutic targets.

Conclusions

In this review, we discuss the potential application of lncRNAs for the monitoring and treatment of breast cancer. We conclude that lncRNAs play important roles in the pathophysiology of this disease and may serve as putative therapeutic targets. As such, tumor-specific lncRNAs may be instrumental for improving current breast cancer clinical practices.

https://ift.tt/2yzH7fv

CCL18 secreted from M2 macrophages promotes migration and invasion via the PI3K/Akt pathway in gallbladder cancer

Abstract

Purpose

The presence of M2 macrophages within primary tumors has been correlated with a poor prognosis for many types of cancer. However, little is known about the role of M2 macrophages in gallbladder cancer (GBC).

Methods

The number of M2 macrophages in 78 GBC and 16 normal gallbladder tissue samples was assessed by immunohistochemistry. The THP-1 monocyte cell line was differentiated into M2 macrophages and co-cultured with GBC-derived cell lines. The effect of M2 macrophages on promoting GBC cell migration and invasion was analyzed using migration, invasion and scratch wound healing assays. Western blotting and real-time PCR were used to assess the expression of epithelial-mesenchymal transition (EMT) markers and the activation status of the PI3K/Akt signaling pathway in GBC cells co-cultured with THP-1-derived macrophages.

Results

The average number of M2 macrophages was found to be significantly higher in GBC tissues than in normal gallbladder tissues. We also found that GBC patients with higher M2 macrophage counts exhibited poorer overall survival rates. Co-culture with M2 macrophages significantly promoted the migration, invasion and EMT of GBC cells. Moreover, we found that CCL18 secreted from M2 macrophages had the same effect on GBC cells as M2 macrophages. Blocking the function of CCL18 with a neutralizing antibody reversed this effect. Finally, we found that M2 macrophages could activate PI3K/Akt signaling in GBC cells, thereby leading to migration, invasion and EMT of these cells.

Conclusions

Our findings contribute to our understanding of the role of chronic inflammation in GBC development and progression, and may offer potential therapeutic targets for GBC.

https://ift.tt/2zI8Rzt

Telestroke for Comprehensive Transient Ischemic Attack Care in Acute Stroke Ready Hospitals

Condition: Transient Ischemic Attack
Intervention: Other: Telestroke
Sponsor: University of Minnesota, MN
Recruiting

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FRAIL-IMMUNE (GORTEC 2018-03) - Combination of Durvalumab With Carboplatin/Paclitaxel

Condition: Squamous Cell Carcinoma of the Head and Neck
Intervention: Drug: Durvalumab with Carboplatin/Paclitaxel
Sponsor: Centre Leon Berard
Not yet recruiting

https://ift.tt/2Jrcltt

Phase 1b/2a Study of Vactosertib in Combination With Pembrolizumab in Metastatic Colorectal Cancer or Gastric Cancer

Conditions: Metastatic Colorectal Cancer; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma
Intervention: Drug: TEW-7197
Sponsors: MedPacto, Inc.; Merck Sharp & Dohme Corp.
Not yet recruiting

https://ift.tt/2Dd8NdZ

Telestroke for Comprehensive Transient Ischemic Attack Care in Acute Stroke Ready Hospitals

Condition: Transient Ischemic Attack
Intervention: Other: Telestroke
Sponsor: University of Minnesota, MN
Recruiting

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FRAIL-IMMUNE (GORTEC 2018-03) - Combination of Durvalumab With Carboplatin/Paclitaxel

Phase 1b/2a Study of Vactosertib in Combination With Pembrolizumab in Metastatic Colorectal Cancer or Gastric Cancer

Making a difference in gender disparities

Across the globe, women are made vulnerable by modifiable determinants in their homes, communities and cultures. In "Barriers to healthcare for female patients in Papua New Guinea," Klaver and Coe address some of this risk. The authors present the case of a 25 year old woman who had complaints of abdominal distension, exertional dyspnea and amenorrhea. Despite trying to address these symptoms early on, she "had been turned away… [d]ue to limited resources and high levels of tribal fighting in the area…. The closest hospital where elective surgery was available was a 10-hour journey by dirt road for which she had neither transport nor funds to allow her to travel." Her husband had left her and taken a second wife due to her illness, and she had moved back to her family and was raising her child alone. "She currently had no contact with or financial support from her husband." She was diagnosed with HIV, treatment was initiated, and three months later had an ovarian cyst of 5.3 kg (12% of her body weight) removed in an uneventful elective surgery.

While there are multiple reasons for her delayed presentation to care and the severity of her symptoms, the authors make clear that tribal violence in the highlands of Papua New Guinea was a major factor in her delayed presentation. First, "Women are commonly targeted in the tribal fighting and subjected to rape and sexual violence as part of the conflict." Second, "Due to high levels of trauma and significant numbers of patients requiring emergency surgery… [the hospital] did not undertake elective procedures." Both of these facets of the tribal violence conspired against this patient to ensure she would remain in poor health.^[1]

Papua New Guinea is the only country in the pacific where women have a lower life expectancy than men. As described by the authors, "Many women are only allowed to attend… hospitals with the permission of their husbands, and any surgical procedure would certainly require… [his] consent." Many women in abusive relationships have no other options but to return to their abuser.^[2] Her amenorrhea caused her husband to abandon her for a second wife, and she was forced to provide for herself despite her condition. The author's hypothesize, "Had [her ill health]… not prevented her from working, she would likely never have voluntarily attended the hospital." These gender disparities are worsened in diseases associated with cultural stigma, such as HIV.^[3]

While the outcome from this case can be construed as positive, this woman still suffered for years because of discrimination against her gender. This is not only a problem in Papua New Guinea, but worldwide. Health professionals can act as advocates for these patients by ensuring they receive the proper care, being aware of the gender biases present in each culture, and fighting for their patients on a local, national and global level.

BMJ Case Reports invites authors to submit global health case reports that describe the disparities of healthcare based on gender. These cases could focus on:

-The factors contributing to these disparities

-The methods used to ensure equal care for all

-The unique contributions made by female practitioners in areas of gender disparities.

Manuscripts may be submitted by students, physicians, nurses and allied health professionals to BMJ Case Reports at www.bmjcasereports.com. For more information, review our guidance on how to write a global health case report and look through our online collection

To read more about gender disparities at BMJ Case Reports, please review:

-'The more we change, the more we remain the same': female feticide continues unabated in India

– Barriers to safe abortion access: uterine rupture as complication of unsafe abortion in a Ugandan girl

-HIV in India: the Jogini culture

To read more about gender disparities globally from other cited sources, please review:

^[1]ICRC report, 2016. The old ways are gone: Papua New Guinea's tribal wars become more destructive. Available at https://medium.com/@ICRC/the-old-ways-are-gone-papua-new-guineas-tribal-wars-become-more-destructive-ade38205196f

^[2]MSF, 2016. Papua New Guinea Report- "Return to abuser". http://www.msf.org/sites/msf.org/files/msf-pngreport-def-lr.pdf

^[3] Wardlow H. The (extra)ordinary ethics of being HIV-positive in rural Papua New Guinea. J R Anthropol Inst 2017;23:103–19.doi:10.1111/1467-9655.12546

The post Making a difference in gender disparities appeared first on BMJ Case Reports blog.

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Assessment of anxiety and stress markers in children submitted to educational strategies and ART-restoration: a randomized clinical trial

Publication date: Available online 29 October 2018

Source: Archives of Oral Biology

Author(s): Juana Rosmeri Salas Huamani, Taís de Souza Barbosa, Camila Nobre de Freitas, Karina Guedes de Sousa, Maria Beatriz Duarte Gavião, Soraya Coelho Leal, Fábio Luiz Mialhe, Paula Midori Castelo

Abstract

Objective

Although atraumatic restorative treatment (ART) is considered to be a good option for anxious patients, there is a lack of information whether ART associated to oral health educational strategy (OHES) would positively influence the level of anxiety and stress in children. This study aimed to evaluate the impact of OHES on anxiety and stress markers of schoolchildren submitted to ART.

Design

A sample of 78 six- to eight-year-old schoolchildren, with carious lesions in dentin, were randomly divided into groups: OHES + ART-group (n = 39) and ART-group (n = 39). OHES consisted of an educational interactive strategy performed once a week for four weeks. ART was performed using a standardized procedure with hand instruments and glass-ionomer cement. Anxiety and stress markers were assessed subjectively by the modified Venham Picture Test (m-VPT), modified Venham Anxiety Scale (m-VAS), while objective measures consisted of heart rate (HR) and salivary cortisol and alpha-amylase levels evaluated before, during and after treatment.

Results

The two groups did not differ in the perceived anxiety and in anxious behavior, and the variation along the treatment was not significant in both groups (p > 0.05). Both groups also showed higher HR "Before ART-restoration" than the other time-points as an anticipatory anxiety. ART group showed higher HR than OHES + ART group during the "Explanation of procedure" (p = 0.041) and "Deep excavation" (p = 0.018), and only ART group showed higher amylase levels "Before ART" compared to "After ART" (p = 0.004).

Conclusions

It was concluded that OHES associated with ART showed a positive effect in modulating heart rate and alpha-amylase levels, that is, those markers of stress objectively measured during ART-restoration.

https://ift.tt/2yFxVpI

Macrophage-mediated repair of intraepithelial damage in rat oral mucosa

Publication date: Available online 29 October 2018

Source: Archives of Oral Biology

Author(s): Yasuna Myose, Hisako Hikiji, Toshiyuki Tsujisawa, Kazuo Sonoki, Naomi Yada, Hiromasa Inoue

Abstract

Objective

It is important to protect the patient's oral mucosa from injury caused by inappropriate oral care. We established anin vivo model of intraepithelial injury of the oral mucosa and assessed the effects of inappropriate dental apparatus use on inflammatory response of macrophages in rats.

Design

Using this model, swabbing was performed to the labial mucosa of rats with the interdental brush, and the tissue samples were processed for histological evaluation.

Results

CD 68-positive macrophage-like cells appeared only in the subepithelial region after intraepithelial injury in the presence and absence of antibiotics. After intraepithelial injury, interleukin-1β levels did not increase beyond those observed in intact rats. The number of bacteria in the lip increased slightly and decreased promptly. In the ear, intraepithelial injury caused an inflammatory response with macrophages infiltrating into the intraepithelial region as well as the subepithelial region, increased interleukin-1β production, and high bacterial levels around tissues.

Conclusion

Our results highlight the importance of protecting against the intraepithelial injury during oral care procedures, and these findings would contribute to oral care risk management in the future.

https://ift.tt/2OdcS2U

Diazepam as attenuator of pain induced by dentin hypersensitivity in rats exposed to stress

Publication date: Available online 29 October 2018

Source: Archives of Oral Biology

Author(s): Márcia Tonetti Ciaramicoli, Fernanda Kabadayan, Maria Martha Bernardi, Ivana Barbosa Suffredini, Cintia Helena Coury Saraceni

Abstract

The pain in dentin hypersensitivity (DH) has distinct sensory and emotional origins, with variations that occur in different intensities for each individual. The aim of this study is to evaluate the effects of diazepam in the attenuation of the pain induced by DH. Design: Fifty male Wistar rats were divided into five groups: control group received water ad libitum (C); stress group received water ad libitum plus stress (S); DH induced by erosion challenge with isotonic solution ad libitum (G); DH and stress (GS); and DH, stress and diazepam (GSD) groups. Animals of the GS group were exposed to the New York Subway Stress Model. Animals treated with diazepam (GSD group) received 1 mg/kg every 3 days, from the 15th day of treatment until the end of the stress-inducing period. The body weights of rats were weekly registered. After 30 days, all groups were submitted to the DH test, which was assessed using cold water stimuli, and were graded 0, 0.5, 1, 2, or 3. Dental elements were evaluated using scanning electron microscopy (SEM). Results: 1) Groups G and GS presented the highest DH scores, which confirms that stress increased pain response; 2) GSD group had significantly reduced DH scores compared to G and GS groups; 3) SEM of dental elements showed exposed dentin tubules in G, GS, and GSD groups, as expected. Conclusions: diazepam attenuated pain induced by dentin hypersensitivity in rats exposed to stress.

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RUNX2 mutation impairs osteogenic differentiation of dental follicle cells

Publication date: Available online 29 October 2018

Source: Archives of Oral Biology

Author(s): Yang Liu, Xiangyu Sun, Xianli Zhang, Xiaozhe Wang, Chenying Zhang, Shuguo Zheng

Abstract

Objectives

Cleidocranial dysplasia (CCD), mainly caused byRUNX2 mutation, is a dominantly inherited skeletal disorder with many dental abnormalities, characterized by delayed permanent tooth eruption. In this study, we explored a novel RUNX2 mutation and the effect of RUNX2 mutation on osteogenic differentiation of dental follicle cells (DFCs).

Design

A CCD patient with typical clinical features was involved in this study. Conservation and secondary structural analysis of theRUNX2 mutation was first performed. Then DFCs that stably expressing wild-type or mutant RUNX2 were established using lentiviruses. Cell Counting Kit 8 (CCK8) assays were performed to test the proliferation of DFCs. Measurement of alkaline phosphatase (ALP) activity, ALP staining, alizarin red staining and determination of osteoblast-specific genes expression were performed to assess osteogenic capacity of DFCs.

Results

A missense mutation (c.674 G > T, p. R225 L) ofRUNX2 gene was identified in the CCD patient. Conservation and secondary structural analysis revealed that the mutation was located in highly conserved Runt domain and altered secondary structure of RUNX2. CCK8 assays showed that mutant RUNX2 increased the proliferation rate of DFCs compared to wild-type RUNX2. ALP activity, ALP staining and alizarin red staining results indicated that mutant RUNX2 decreased the mineralization ability of DFCs. In addition, mutant RUNX2 significantly down-regulated the expression of osteoblast-associated genes.

Conclusions

RUNX2 mutation can reduce the osteogenic capacity of DFCs by inhibiting osteoblast-associated genes and then affecting bone formation, which participates in bone remodeling during tooth eruption. These effects may be partly responsible for the defects in permanent tooth eruption of CCD patients.

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Relationships between craniofacial morphology and masticatory muscle activity during isometric contraction at different interocclusal distances

Publication date: Available online 29 October 2018

Source: Archives of Oral Biology

Author(s): Tamiyo Takeuchi-Sato, Taro Arima, Michael Mew, Peter Svensson

Abstract

Objective

The aim was to investigate relationships amongst interocclusal distances, masticatory muscle electromyographic (EMG) activity during isometric contraction of masticatory muscles, and craniofacial morphology.

Design

Twenty-eight women and 12 men (25.3 ± 3.8 years old) participated. After measuring maximal voluntary occlusal bite force (MVOBF) between the right-first premolars, the participants were asked to bite at submaximal levels of 0 (= holding the bite force transducer), 15, 22.5, and 30% MVOBF with the use of visual feedback. The thickness of a bite force transducer was set at 10, 12, 13, 14, 16, 17, 18, 19, 20, 22, and 24 mm (= interocclusal distance: IOD). Nine soft tissue craniofacial factors were assessed through digital photograph: face height, middle face height, lower face height, face width, inter-pupil distance and mandibular plane angle, lower face height / face height ratio, inter-pupil distance / facial width ratio and face width / face height ratio.

Results

In the masseter muscle, EMG activity decreased with increased IODs. The participants with higher mandibular plane angle had more negative slope coefficients of IOD-EMG graphs at 0% MVOBF especially in male temporalis and female masseter and temporalis muscles, suggesting that a greater mandibular plane angle is associated with lower EMG activity at longer IOD.

Conclusions

Overall the findings support the notion that craniofacial morphology is associated with differences in neuromuscular activity of the masticatory muscles, and suggest that the neuromuscular effects of oral appliances may be dependent on patients' craniofacial morphology and the thickness of the device. (247/250 words)

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Runx1 regulates osteogenic differentiation of BMSCs by inhibiting adipogenesis through Wnt/β-catenin pathway

Publication date: Available online 29 October 2018

Source: Archives of Oral Biology

Author(s): Yuan Luo, Yingdi Zhang, Guojun Miao, Yiwen Zhang, Yuehua Liu, Yuanliang Huang

Abstract

Objective

Bone marrow stem cells (BMSCs) can commit to both adipocyte and osteoblast lineages. However, the mechanism underlying how transcription factors regulate this process remains elusive. Our aims were to determine the role of runt-related transcription factor 1 (Runx1) in BMSCs lineage determination and the underlying mechanisms.

Study Design

BMSCs from mouse femur bone marrow were harvested and cultured in osteogenic medium. Runx1 was knocked down in BMSCs using lentivirus. Alkaline phosphatase (ALP), Von Kossa and Oil Red O staining were performed on the Runx1-transduced BMSCs and control cells to see the differences of osteogenic and adipogenic differentiation in these groups. Real-time quantitative PCR and Western blot were performed to analyse the expression levels of osteogenic and adipogenic factors regulated by Runx1 at gene and protein levels.

Results

In BMSCs with Runx1 knockdown, the expression levels of osteogenic-related genes decreased significantly while the adipogenic genes C/EBPα, PPARγ and Fabp4 increased by 12-fold, 10-fold, and 30-fold, respectively, compared with the control cells. ALP activity and Von kossa staining were greatly decreased in Runx1-transfected cells while the Oil Red O staining was comparable to that in the control groups. Canonical Wnt signaling was investigated in the Runx1-deficient BMSCs, and a 50% decrease in the expression of active β-catenin in these cells was found. Lef1 and Tcf1, which are regulated by β-catenin were also decreased in Runx1-deficient cells compared with the levels in controls. Moreover, although there was no difference in the expression of Wnt3a among the three groups of cells, the expression of Wnt10b decreased by 80% in Runx1-deficient BMSCs compared with the levels in the other two groups.

Conclusions

Our results show Runx1 promotes the capacity of osteogenesis in BMSCs while inhibits their adipogenesis through canonical Wnt/β-catenin pathway, which provides new insights into osteoblast development.

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Novel dental phenotype in non-syndromic Pierre Robin Sequence: a retrospective study

Publication date: Available online 29 October 2018

Source: Archives of Oral Biology

Author(s): Jose Francisco Mateo-Castillo, Otavio Pagin, Izabel Maria Marchi Carvalho, Tulio Lorenzo Olano-Dextre, Lucimara Teixeira das Neves

Abstract

Objective

The objective was to investigate dental phenotypes in individuals with non-syndromic Pierre Robin Sequence (ns-PRS) and compare the prevalence of these phenotypes with subjects with non-syndromic cleft palate (ns-CP) and a control group with subjects without any craniofacial anomalies.

Methods

A total of 760 panoramic radiographs of 330 individuals (110 with ns-PRS; 110 with ns-CP and 110 without any malformations) were digitized and evaluated regarding the diagnosis of taurodontism, tooth agenesis, root dilaceration and tooth transposition. Chi-square test was applied to compare the occurrence of dental phenotypes between groups. A P value of less than 0.05 was considered statistically significant.

Results

Total prevalence of dental phenotypes was 94.5% of ns-PRS; 54.5% of ns-CP and 59.1% of the control group subjects with a statistically significant difference for the ns-PRS when compared to the other two groups. Two dental phenotypes, taurodontism and dental agenesis were identified with statistically significant higher prevalences in subjects with ns-PRS when compared with the ns-CP group and the control group (p < 0.001). Taurodontism was the most prevalent dental phenotype, with 92.73% in the ns-PRS group, 40.91% for ns-CP and 44.55% in the control group. Tooth agenesis had a prevalence of 22.7% for ns-PRS, 4.5% for ns-CP and no case in the control group. For the prevalence of root dilaceration and tooth transposition, no statistically significant differences were observed between the three groups.

Conclusions

Due to the high frequency of taurodontism in individuals with ns-PRS, we suggested that this novel phenotype would be important in the phenotypic screening of ns-PRS and could be considered as a phenotype associated with ns-PRS.

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Analysis of sulfated glycosaminoglycan composition change in intrinsically aged and photoaged human skin using an enzymatic degradation method

Publication date: Available online 30 October 2018

Source: Journal of Dermatological Science

Author(s): Jang-Hee Oh, Min Kyeong Shin, Hanon Lee, Jiyeong Lim, Mira Choi, Soyun Cho, Jin Ho Chung

https://ift.tt/2AAcsQv

The role of APRIL - A proliferation inducing ligand - In autoimmune diseases and expectations from its targeting

Publication date: Available online 30 October 2018

Source: Journal of Autoimmunity

Author(s): Laurie Baert, Benoit Manfroi, Olivier Casez, Nathalie Sturm, Bertrand Huard

Abstract

Autoimmunity occurs when an adaptive immune response is directed against a self-antigen. As such, autoimmune reactions associated with the production of autoantibodies are common. These autoantibodies may either be pathogenic by inducing the initial damage to self, or exacerbate the reaction secondarily to the initial damage. In both cases, the pathway(s) leading to exposure of the immune system to the self-antigen inducing the production of autoantibodies is largely unknown. The latter is largely complicating the setting of putative prophylactic treatments. As a consequence, one possible way to control these diseases is to eliminate the cells producing antibodies. We will see that this approach is not yet part of any treatment in autoimmunity. Indeed, all the currently available non-specific immunosuppressive treatments do not target directly quiescent antibody-producing plasma cells. However, treatments aimed at depleting precursors of plasma cells, mature B-lymphocytes and/or antigen-experienced B cells not yet fully differentiated into plasma cells, are emerging. Such strategies were recently proven to be highly successful in several autoimmune disorders by two independent ways. The first way is by induction of B-cell cytotoxicity with an antibody directed against the surface antigen CD20. The second way is by antagonism of a key B-cell survival factor, the B-cell activation factor from the TNF superfamily (BAFF). In the present review, we will focus on the current knowledge regarding the role of a molecule related to BAFF, a proliferation-inducing ligand (APRIL), in autoimmune diseases, which acts on antibody-producing plasma cells. We will discuss expectations deriving from APRIL targeting in autoimmune diseases.

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Etiopathogenesis of autoimmune hepatitis

Publication date: Available online 29 October 2018

Source: Journal of Autoimmunity

Author(s): Annarosa Floreani, Paula Restrepo-Jiménez, Maria Francesca Secchi, Sara De Martin, Patrick S.C. Leung, Edward Krawitt, Christopher L. Bowlus, M. Eric Gershwin, Juan-Manuel Anaya

Abstract

Autoimmune hepatitis is a chronic inflammatory liver disease characterized by hypergammaglobulinemia, the presence of autoantibodies, and inflammation within the liver, including lymphocytic infiltrates and interface hepatitis. Autoimmune hepatitis shows a female predominance and can present at any age and in any ethnicity. The disease is thought to be a consequence of a break of immune tolerance leading to an autoimmune process that induces liver injury. The self-attack is triggered by T-helper cell-mediated liver autoantigen recognition and B-cell production of autoantibodies, and is sustained by impaired regulatory T cells number and function. Superimposed on a genetic predisposition, infections and environmental factors have been studied as triggering factors for the disease. Allelic variants in the HLA locus have been associated with susceptibility; associations with single nucleotide polymorphisms within non-HLA genes have also been assessed. Several factors have been described as triggers of autoimmune responses in predisposed individuals, including infections, alcohol, vitamin D deficiency, and an altered composition of the intestinal microbiome. Importantly, drugs and herbal agents may trigger classical autoimmune hepatitis, or may induce a liver disease with autoimmune features. Interactions between female hormones and genetic factors have been hypothesized to play a role in autoimmunity, although the exact role for these factors has not been fully established. Herein we present a review of the etiology of autoimmune hepatitis including de novo autoimmune hepatitis post-liver transplantation as well as animal models for its study.

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The landscape and diagnostic potential of T and B cell repertoire in Immunoglobulin A Nephropathy

Publication date: Available online 29 October 2018

Source: Journal of Autoimmunity

Author(s): Chen Huang, Xuemei Li, Jinghua Wu, Wei Zhang, Shiren Sun, Liya Lin, Xie Wang, Hongmei Li, Xiaolei Wu, Peng Zhang, Guoshuang Xu, Hanmin Wang, Hongbao Liu, Yuzhen Liu, Dapeng Chen, Li Zhuo, Wenge Li, Huanming Yang, Jian Wang, Ling Wang

Abstract

Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. The pathologic hallmark of IgAN is immune complex deposited in glomerular mesangium, which induces inflammation and affects the kidney's normal functions. The exact pathogenesis of IgAN, however, remains obscure. Further, in current clinical practice, the diagnosis relies on needle biopsy of renal tissue. Therefore, a non-invasive method for diagnosis and prognosis surveillance of the disease is highly desirable. To this end, we investigated the T cell receptor beta chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire in circulating lymphocytes and compared them with kidney infiltrating lymphocytes using immune repertoire high throughput sequencing. We found that some features of TCRB and IGH in renal tissues were remarkably different from that in the blood, including decreased repertoire diversity, increased IgA and IgG frequency, and more antigen-experienced B cells. The complementarity-determining region 3 (CDR3) length of circulating TCRB and IGH in IgAN patients was significantly shorter than that in healthy controls, which is the result of both VDJ rearrangement and clonal selection. The IgA1 frequency in the blood of IgAN patients is significantly higher than that in other Nephropathy (NIgAN) patients and healthy control. Importantly we identified a set of TCRB and IGH clones, which can be used to distinguish IgAN from NIgAN and healthy controls with high accuracy. These results indicated that the TCRB and IGH repertoire can potentially serve as non-invasive biomarkers for the diagnosis of IgAN. The characteristics of the kidney infiltrating and circulating lymphocytes repertoires shed light on IgAN detection, treatment and surveillance.

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Abnormal positioning of the common carotid artery clinically diagnosed as a submandibular mass

Abstract

The common carotid artery (CCA) usually runs along the long axis of the neck, although it is occasionally found in an abnormal position or is displaced. We report a case of an 86-year-old woman in whom the CCA was identified in the submandibular area. The patient visited our clinic and reported soft tissue swelling in the right submandibular area. It resembled a tumor mass or a swollen lymph node. Computed tomography showed that it was the right CCA that had been bent forward and was running along the submandibular subcutaneous area. Ultrasonography verified the diagnosis. No other lesions were found on the diagnostic images. Consequently, the patient was diagnosed as having abnormal CCA positioning. Although this condition generally requires no treatment, it is important to follow-up the abnormality with diagnostic imaging because of the risk of cerebrovascular disorders.

https://ift.tt/2OfM2r0

Evaluating the mandibular condyles of patients with osteoarthritis for bone marrow abnormalities using magnetic resonance T2 mapping

Abstract

Objectives

This study investigated whether erosion and osteophyte correlates with condyle bone marrow abnormalities (BMA), as detected with quantitative T2 mapping.

Methods

Fifty-six joints (in 44 patients) that demonstrated evidence of bony erosion (ER) or osteophytes (OS) related to disc displacement without reduction were studied with MR images. A control group of 50 joints (in 50 patients) was included. The subjects were divided into five groups; noAR (control), noBMA-ER, BMA-ER, noBMA-OS, and BMA-OS. T2 mapping was performed and the regions of interest were placed over the bone marrow at the top of the condyle. The mean T2 values of the bone marrow of the mandibular condyle were calculated for all mapping images. After assessing age-related changes in T2 values of noAR group using Pearson's product-moment, differences in median T2 values of five groups were analyzed using Kruskal–Wallis test, and Steel–Dwass test (p < 0.05).

Results

There was no significant correlation between age and T2 value in noAR group. The median T2 values of noBMA-ER and BMA-ER groups were significantly higher than those of noAR, noBMA-OS and BMA-OS groups. Those of noBMA-OS and BMA-OS groups were significantly lower than those of noAR, noBMA-ER and BMA-ER groups. There was no significant difference between noBMA and BMA groups.

Conclusions

It is suggested that erosion and osteophyte of the condyle may correlate with bone marrow abnormalities. T2 mapping could be show slight marrow changes of the arthritic condyle.

https://ift.tt/2yGAJ65

Work-related laryngeal cancer: Trends in France from 2001 to 2016

Publication date: Available online 29 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): J. Grignoux, Q. Durand-Moreau, N. Vongmany, S. Brunel, Rnv3p members, J.-D. Dewitte

Abstract

Objectives

As part of the 2014–2019 cancer plan and in order to improve our knowledge of work-related cancers, we analysed the work-related laryngeal cancer risk situations identified in the French national occupational disease surveillance and prevention network (rnv3p) from 2001 to 2016.

Material and methods

This study focused on cases of work-related laryngeal cancer, which the expert physician considered to be directly related to exposure (intermediate or strong causal relationship). Demographic data, occupational exposure circumstances (hazards, occupation, business sector), non-occupational risk factors and the occupational physician's opinion concerning notification as an occupational disease were analysed.

Results

Two hundred forty-four cases of laryngeal cancer were registered between 2001 and 2016. One hundred and forty seven cases were considered to be work-related, with an intermediate or strong causal relationship in 87 cases. This exclusively male population had a median age of 59 years. Ninety-seven different forms of exposure were identified, including asbestos in 78 cases. The main business sectors concerned were specialized construction (14 cases) and metallurgy (7 cases). Occupational disease notification was recommended in 60 patients, corresponding to asbestos exposure in 80% of cases.

Conclusions

Asbestos is the laryngeal cancer risk factor most commonly reported in the network from 2001 to 2016. This study confirms the role of asbestos in laryngeal carcinogenesis. Laryngeal cancer may therefore need to be compensated as an occupational disease in France, as in other European countries.

https://ift.tt/2DcOAoQ

Risk factors for oral health in young, urban, Aboriginal and Torres Strait Islander children

Australian Dental Journal, Volume 0, Issue ja, -Not available-.

https://ift.tt/2RlzY9B

The potential ecological effects of Casein Phosphopeptide‐Amorphous Calcium Phosphate in dental caries prevention

Australian Dental Journal, Volume 0, Issue ja, -Not available-.

https://ift.tt/2PsI2Ih

Process Evaluation of the Midwifery Initiated Oral Health‐Dental Service Program: Perceptions of Pregnant Women

Australian Dental Journal, Volume 0, Issue ja, -Not available-.

https://ift.tt/2Rr1DGd

The Salt-Inducible Kinases: Emerging Metabolic Regulators

Publication date: Available online 29 October 2018

Source: Trends in Endocrinology & Metabolism

Author(s): Kei Sakamoto, Laurent Bultot, Olga Göransson

The discovery of liver kinase B1 (LKB1) as an upstream kinase for AMP-activated protein kinase (AMPK) led to the identification of several related kinases that also rely on LKB1 for their catalytic activity. Among these, the salt-inducible kinases (SIKs) have emerged as key regulators of metabolism. Unlike AMPK, SIKs do not respond to nucleotides, but their function is regulated by extracellular signals, such as hormones, through complex LKB1-independent mechanisms. While AMPK acts on multiple targets, including metabolic enzymes, to maintain cellular ATP levels, SIKs primarily regulate gene expression, by acting on transcriptional regulators, such as the cAMP response element-binding protein-regulated transcription coactivators and class IIa histone deacetylases. This review describes the development of research on SIKs, from their discovery to the most recent findings on metabolic regulation.

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Der Heilpraktiker – aktuelle Informationen zu einem „schwierigen“ Berufsbild

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Therapie der rezidivierten und fernmetastasierten Plattenepithelkarzinome des Kopf-Hals-Bereichs

Zusammenfassung

In diesem Jahr wurde die Therapie von Patienten mit rezidivierten und metastasierten Plattenepithelkarzinomen des Kopf-Hals-Bereichs (R/M-HNSCC) vorrangig von der Immuntherapie dominiert. Die entsprechenden Arbeiten werden in einem gesonderten Artikel präsentiert. Darüber hinaus wurden auf dem ASCO-Kongress insbesondere Ergebnisse von Phase-II-Studien präsentiert, in denen wie auch in den letzten Jahren der Einsatz neuerer Medikamente (monoklonale Antikörper, „small molecules") eine große Rolle spielt. Des Weiteren wurde ein klinisches Scoringsystem zur Evaluation der Prognose bei R/M-HNSCC vorgestellt und der Einfluss des HPV-Status auf das Überleben in dieser Patientenkohorte untersucht. Die nun hier vorgestellten Studien geben die verschiedenen Konzepte der medikamentösen Behandlung von R/M-HNSCC wieder und repräsentieren die Vielfalt der Therapieansätze in der Rezidiv- und Metastasensituation.

https://ift.tt/2Pr04e5

Hybridprothese als schädelbasisnahes Interponat für die A. carotis interna bei radikaler Entfernung eines äußerst seltenen malignen Glomus-caroticum-Paraganglioms

Zusammenfassung

Hintergrund

Halstumoren sind hinsichtlich ihres adäquaten diagnostischen und therapeutischen Managements anspruchsvoll, v. a. bei malignitätsbedingtem infiltrativen Wachstum, die versorgungsrelevante Gefäße einbeziehen, zur Erreichung eines prognosebestimmenden R0-Resektionsstatus.

Ziel

Ziel des Fallberichts über den Kasus eines seltenen vaskulär infiltrierenden malignen Glomus-caroticum-Tumors (Paragangliom) war es, die erfolgreiche interdisziplinär-operative Versorgung durch HNO und Gefäßchirurgie wegen notwendiger operativer Reintervention mit zusätzlicher Gefäßresektion infolge histologisch nachgewiesener Malignität des Erstresektates unter Verwendung einer Hybridprothese für den A.-carotis-interna-Ersatz nahe der Schädelbasis zu präsentieren.

Fall

Ein 38-jähriger Patient wurde wegen eines verschieblichen Halstumors der rechten Seite mittels MRA und DSA diagnostiziert, der Tumor embolisiert und anschließend unter Verwendung eines Propaten-Gefäßersatzes (7 cm; W.L. Gore GmbH, Putzbrunn, Deutschland) zwischen Aa. carotis communis et interna operiert – Histologie: malignes Paraganglioma caroticum von 40 mm Durchmesser mit Haemangiosis et Lymphangiosis carcinomatosa, was zur Reoperation veranlasste („neck dissection" [Level II, III, IV, V]) und eine Lymphknotenmetastase zeigte. Es folgte eine Revision der Gefäßrekonstruktion mit GORE® Hybrid Vascular Graft Prothesenstent (W.L. Gore GmbH) als Interponat wegen des kurzen extrakraniellen Gefäßstumpfes der distalen A. carotis interna nahe der Schädelbasis und zur Limitierung der Abklemmzeit. Das frühpostoperative Outcome war komplikationslos, nach 24 Monaten besteht kein Anhalt für ein Tumorrezidiv.

Schlussfolgerung

Ausgedehnte Resektionen notfalls auch unter Mitnahme von (arteriellen) Gefäßsegmenten dienen der Erreichung einer onkologischen R0-Situation wie bei dieser extrem seltenen und anspruchsvollen Tumorentität. Hybridprothesen ermöglichen dabei die zeitsparende Gefäßrekonstruktion und die Minderung von Ischämiezeiten um >50 %.

https://ift.tt/2RoxIhD

Chemotherapy resistance and stemness in mitotically quiescent human breast cancer cells identified by fluorescent dye retention

Abstract

Metastatic recurrence in breast cancer is a major cause of mortality and often occurs many years after removal of the primary tumour. This process is driven by the reactivation of disseminated tumour cells that are characterised by mitotic quiescence and chemotherapeutic resistance. The ability to reliably isolate and characterise this cancer cell population is critical to enable development of novel therapeutic strategies for prevention of breast cancer recurrence. Here we describe the identification and characterisation of a sub-population of slow-cycling tumour cells in the MCF-7 and MDA-MB-231 human breast cancer cell lines based on their ability to retain the lipophilic fluorescent dye Vybrant^® DiD for up to six passages in culture. Vybrant^® DiD-retaining (DiD+) cells displayed significantly increased aldehyde dehydrogenase activity and exhibited significantly reduced sensitivity to chemotherapeutic agents compared to their rapidly dividing, Vybrant^® DiD-negative (DiD−) counterparts. In addition, DiD+ cells were exclusively capable of initiating population re-growth following withdrawal of chemotherapy. The DiD+ population displayed only partial overlap with the CD44⁺CD24^−/low cell surface protein marker signature widely used to identify breast cancer stem cells, but was enriched for CD44⁺CD24⁺ cells. Real-time qPCR profiling revealed differential expression of epithelial-to-mesenchymal transition and stemness genes between DiD+ and DiD− populations. This is the first demonstration that both MCF-7 and MDA-MB-231 human breast cancer lines contain a latent therapy-resistant population of slow-cycling cells capable of initiating population regrowth post-chemotherapy. Our data support that label-retaining cells can serve as a model for identification of molecular mechanisms driving tumour cell quiescence and de novo chemoresistance and that further characterisation of this prospective tumour-reinitiating population could yield novel therapeutic targets for elimination of the cells responsible for breast cancer recurrence.

https://ift.tt/2zbQxxe

Influence of ambient air pressure changes on vestibular symptoms after stapes surgery

Publication date: Available online 29 October 2018

Source: Auris Nasus Larynx

Author(s): Konrad Johannes Stuermer, Stella Sanader, Heinz Dieter Kluenter, Karl-Bernd Hüttenbrink

Abstract

Objective

To examine if vestibular irritation after stapes surgery may be provoked by pressure changes across the tympanic membrane, which consecutively results in displacements of the ossicular chain and the piston prosthesis suspended to it.

Methods

In this prospective study 15 patients (13 female, 2 male) received unilateral stapes surgery (4 left, 11 right ear) with stapedotomy (n = 14) or stapedectomy (n = 1) at an academic tertiary referral center. Surgery was performed under local anesthesia via a transmeatal approach with a piston prosthesis 0.4 × 4.5 mm. The fixation of the stapes, the exclusion of a malleus head fixation, and the gliding capacity of the malleus-incus joint were examined intraoperatively. A pure tone audiogram at four frequencies, a tympanometry with simultaneous video-oculography (VOG), caloric testing, and posturography with and without simultaneous tympanometry were performed six days before surgery, six weeks and three months after surgery, respectively.

Results

The mean air bone gap improved significantly from 25 (±8) dB preoperatively to 10 (±6) dB after surgery. In the tympanometry with simultaneous VOG only two patients showed nystagmus beats into the operated ears during only one of the two follow-up appointments. All other patients did not show any vestibular symptoms or nystagmus during any of the follow-up appointments. In the combined testing of posturography and tympanometry no patient showed any pathological findings.

Conclusion

In patients who underwent stapes surgery with a piston prosthesis no vestibular symptoms can be provoked by pressure changes in the external auditory canal.

https://ift.tt/2qlvJPD

Hypogonadotropic Hypogonadism and Kleefstra Syndrome due to a Pathogenic Variant in the EHMT1 Gene: An Underrecognized Association.

Hypogonadotropic Hypogonadism and Kleefstra Syndrome due to a Pathogenic Variant in the EHMT1 Gene: An Underrecognized Association.

Case Rep Endocrinol. 2018;2018:4283267

Authors: Torga AP, Hodax J, Mori M, Schwab J, Quintos JB

Abstract
Kleefstra syndrome is a genetic condition characterized by intellectual disability, childhood hypotonia, and facial dysmorphisms. Genital anomalies such as micropenis, cryptorchidism, and hypospadias have been reported in 30-40% of males diagnosed with the disease. However, endocrinological investigations have been limited. We describe a case of an adolescent male with Kleefstra syndrome due to a pathogenic variant in the EHMT1 gene whose workup for isolated micropenis is suggestive of a partial hypogonadotropic hypogonadism. A possible endocrine mechanism of the genital anomaly associated with Kleefstra syndrome is discussed.

PMID: 30370152 [PubMed]

https://ift.tt/2CSScvh

Pyogenic granuloma of the larynx: A rare cause of hemoptysis

Publication date: Available online 29 October 2018

Source: American Journal of Otolaryngology

Author(s): Andrea L. Hanick, Joseph B. Meleca, Paul C. Bryson

Abstract

Pyogenic granuloma (PG) may involve gingival mucosa (granuloma gravidarum) in pregnancy but rarely involves the airway. This case report is perhaps the only reported presentation of PG in the larynx causing hemoptysis at a late stage of pregnancy. On laryngoscopic exam, a vascular, right false vocal fold neoplasm was identified with pathological characteristics consistent with PG. Conclusions: Pyogenic granuloma is a relatively common tumor of pregnancy but rarely involves the larynx. In the case of airway involvement during pregnancy, it is best managed in coordination with the high-risk obstetrical team and can be removed safely via standard microsurgical techniques.

https://ift.tt/2DcJJDV

MTHFR AND ApoE genetic variants association with sudden sensorineural hearing loss

Publication date: Available online 29 October 2018

Source: American Journal of Otolaryngology

Author(s): Armita Kakavand Hamidi, Nasrin Yazdani, Kimia Haj Seyedjavadi, Nakisa Zarabi Ahrabi, Ardavan Tajdini, Keivan Aghazadeh, Mahsa M. Amoli

Abstract

Hypothesis

Although the pathogenesis of sudden sensorineural hearing loss (SSNHL) is not clear, however several causes including genetic factors seems to be implicated. We hypothesized that common genetic variants might be involved in SSNHL.

Background

SSNHL is known to be an idiopathic disease because the causative factors have not been identified. Several causes including genetic and viral infection besides immune system reaction, neurological disorders, medications, etc. have been previously reported. We examined the association between ApoE and MTHFR gene variants in SSNHL.

Methods

This study includes case-control scheme encompassing a total of 177 individuals, include patients inflicted with SSNHL and healthy subjects as control group. Genotyping of MTHFR and ApoE variants was conducted by PCR – RFLP method.

Result

Our study showed that MTHFR rs1801133 allele frequency is significantly different between cases and controls. Also genotype distribution of ApoE was significantly different between patients and healthy controls.

Conclusions

MTHFR C677T and ApoE gene variant may be associated with sudden sensorineural hearing loss in an Iranian population.

https://ift.tt/2JtPk9q

Clinical efficacy of cognitive behavioral therapy for chronic subjective tinnitus

Publication date: Available online 29 October 2018

Source: American Journal of Otolaryngology

Author(s): Juan Li, Jianhua Jin, Songli Xi, Qian Zhu, Yuqin Chen, Min Huang, Chunyan He

Abstract

Background

Although cognitive behavioral therapy (CBT) has been known with a theoretical basis for tinnitus patients, there still were lack of clinical evidence.

Objective

To evaluate the clinical efficacy of cognitive behavioral therapy (CBT) for treatment of chronic subjective tinnitus.

Methods

One hundred patients with chronic subjective tinnitus patients were randomly divided into control (50 cases) and intervention (50 cases) groups, which received the masking therapy and sound treatment and masking therapy and sound treatment plus CBT. The treatment efficacy was evaluated.

Results

The total effective rate in intervention group was significantly higher than control group (P < 0.01). After treatment, compared with control group, in intervention group the psychotic somatization, interpersonal sensitivity, depression, anxiety, hostility, terror, and phobic anxiety scores in Symptom Checklist-90 and Tinnitus Handicap Inventory score were significantly decreased (P < 0.05), the serum cortisol level was significantly decreased (P < 0.05), and the serum interleukin-2 level was significantly increased (P < 0.05).

Conclusion

Based on the elimination the mood disorders and reduce the stress, CBT can significantly relieve the symptoms of chronic subjective tinnitus.

https://ift.tt/2D9XjrC

Dose adjustment of irinotecan based on UGT1A1 polymorphisms in patients with colorectal cancer

Abstract

Purpose

Irinotecan is effective for metastatic colorectal cancer (mCRC). SN-38 is an active metabolite of irinotecan, which is formed by carboxylesterase and inactivated by UDP-glucuronyltransferase (UGT) 1A1. The UGT enzyme activity is reduced in patients with homozygous mutation in UGT1A1 genes (*6/*6, *28/*28 and *6/*28); thus dose reduction is required for prevention of severe adverse events associated with irinotecan. The present study was designed to investigate the relationship between UGT1A1 polymorphisms and the incidence of adverse events or the therapeutic effect in mCRC patients who received irinotecan.

Methods

Sixty-three mCRC patients who received irinotecan during January 2014 and May 2018 were the subjects of this study. The incidence of adverse events, including diarrhea and neutropenia, and the therapeutic effect of irinotecan were compared among homozygous group, heterozygous group and wild-type group. The initial dose of irinotecan was 150 mg/m² in the heterozygous group and wild-type group, while the dose was reduced by 20% (120 mg/m²) in the homozygous group.

Results

The UGT1A1 polymorphisms occurred in 15.9%, 33.3%, and 50.8% for homozygous group, heterozygous group, and wild-type group, respectively. The average dose of irinotecan during overall cycles was not significantly different among three groups, despite the reduction of initial dose in homozygous group. There were no significant differences in the incidence rates of adverse events, tumor response, or time to treatment failure among three groups.

Conclusion

The present study demonstrated that dose reduction by 20% ensured safety and efficacy of irinotecan in mCRC patients with homozygous mutation in UGT1A1 genes.

https://ift.tt/2yI18k3

Penicillin allergy and the law

Approximately 10% of the population carries a label of penicillin allergy. However, on evaluation, only a small minority, approximately 5%, of these patients are found to be truly allergic.1 Subsequently, many patients with a history of penicillin allergy are unnecessarily denied treatment with first-line beta-lactam antibiotics, in favor of less desirable and problematic antibiotics such as fluoroquinolones, vancomycin, and clindamycin. As a result of this prescribing pattern, being labeled penicillin allergic is associated with various poor clinical outcomes such as vancomycin-resistant enterococcus (VRE), Clostridium difficile colitis, and methicillin-resistant Staphylococcus aureus (MRSA).

https://ift.tt/2DbxkjD

Authors’ response

We read with interest these 2 separate correspondences, both authored by employees of Aimmune Therapeutics.1,2 We certainly appreciate their interest in our qualitative research study about motivations for seeking peanut allergy therapy.3 With the potential approval of 2 drugs to help treat peanut allergy in the next year, this is a timely topic. Both queries highlight alleged problems regarding our methods and conclusion and voice rather fervent, somewhat misplaced, comments and inappropriate posturing regarding Aimmune's interpretation of DBV's topline data for their phase 3 trial.

https://ift.tt/2JprmvU

New role for the modern allergist in drug allergy

"Hi, doctor. I am here because I have a mast cell disorder.""Do you have a penicillin allergy?""Well, I am here because I Googled my symptoms and told my doctor that I may have a mast cell disorder.""Do you have a penicillin allergy?""I was not sent here for my penicillin allergy. I had it for over 40 years and my doctors told me to never take penicillins."

https://ift.tt/2DbZriO

Authors’ response

In her letter to the editor, Brown1 has a number of questions for us regarding the pressure required to trigger epinephrine auto-injectors (EAIs) and the methodology to justify the conclusions of our study.2 Her major concern is that the force required to trigger the Emerade (Medeca Pharma AB, Uppsala, Sweden) is not known so the Emerade might not inject at lower trigger forces than other EAIs.

https://ift.tt/2JpZRSL

Information for Readers

https://ift.tt/2Deku4n

Pressure, trigger forces, and epinephrine auto-injectors

The recent article by Dreborg et al1 concluded that Emerade, defined as a low-pressure epinephrine auto-injector, has no risk of intraosseous injection in children and a low risk of subcutaneous injection in adolescents and adults. However, assumptions leading to these conclusions could be incorrect.

https://ift.tt/2JoOc6T

Penicillin allergy

The articles cited in this month's chapter of From the Pages of AllergyWatch focus on penicillin allergy. The literature has been rich with articles that cover this topic in very broad strokes from epidemiology to outcomes measures. These articles complement those found in this month's emphasis for the Annals to update and expand the reader's knowledge in this important aspect of our practice base.

https://ift.tt/2DfPhxw

Information for Authors

https://ift.tt/2JrrevQ

Clarification of epicutaneous immunotherapy trial phase 3 results and methods for qualitative survey design

We are writing in regard to an article by Greenhawt et al1 who report results from a qualitative study intended to "better understand what caregivers value in a therapy and assess their underlying goals in seeking such therapy." We have concerns regarding the report's content in terms of the assessment of the trial to which the authors refer and the survey methodology.

https://ift.tt/2DbZqLM

https://ift.tt/2JquZ4u

Qualitative evaluation of caregiver preferences for peanut immunotherapy products

In the article "Understanding caregiver goals, benefits, and acceptable risks of peanut allergy therapies,"1 the authors undertake the ambitious task of using qualitative research methods to describe the motivation and goals of caregivers of children with peanut allergy. This is a critically important area given the rapid increase in peanut allergy in the past 2 decades and the development of 2 different immunotherapy products, one or both of which will likely be approved by the US Food and Drug Administration and available for prescription by late 2019.

https://ift.tt/2DcGLiL

Editorial Board

https://ift.tt/2JopOlC

Wound healing property of a gel prepared by the combination of Pseudomonas aeruginosa alginate and Alhagi maurorum aqueous extract in rats

Dermatologic Therapy, Volume 0, Issue ja, -Not available-.

https://ift.tt/2qgfwLL

A liposome‐based formulation containing equol, dihomo‐γ‐linolenic acid (DGLA), and propionyl‐L‐carnitine to prevent and treat hair loss: a prospective investigation

Dermatologic Therapy, Volume 0, Issue ja, -Not available-.

https://ift.tt/2Q7bCQv

Does chronic immunosuppressive therapy for autoimmune disease influence the risk of developing active tuberculosis?

Dermatologic Therapy, Volume 0, Issue ja, -Not available-.

https://ift.tt/2qjxj4D

Wound healing property of a gel prepared by the combination of Pseudomonas aeruginosa alginate and Alhagi maurorum aqueous extract in rats

Dermatologic Therapy, Volume 0, Issue ja, -Not available-.

https://ift.tt/2qgfwLL

A liposome‐based formulation containing equol, dihomo‐γ‐linolenic acid (DGLA), and propionyl‐L‐carnitine to prevent and treat hair loss: a prospective investigation

Dermatologic Therapy, Volume 0, Issue ja, -Not available-.

https://ift.tt/2Q7bCQv

Does chronic immunosuppressive therapy for autoimmune disease influence the risk of developing active tuberculosis?

Dermatologic Therapy, Volume 0, Issue ja, -Not available-.

https://ift.tt/2qjxj4D

Immune and Genetic Features of the Chromosome 22q11.2 Deletion (DiGeorge Syndrome)

Abstract

Purpose of Review

This review provides an update on the progress in identifying the range of immunological dysfunction seen in DiGeorge syndrome and on more recent diagnostic and treatment approaches.

Recent Findings

Clinically, the associated thymic hypoplasia/aplasia is well known and can have profound effects on T cell function. Further, the humoral arm of the immune system can be affected, with hypogammaglobulinemia and poor vaccine-specific antibody response. Additionally, genetic testing utilizing chromosomal microarray demonstrates a small but significant number of 22q11 deletions that are not detectable by standard FISH testing. The recent addition of a TREC assay to newborn screening can identify a subset of infants whose severe immune defects may result from 22q11 deletion. This initial presentation now also places the immunologist in the role of "first responder" with regard to diagnosis and management of these patients.

Summary

DiGeorge syndrome reflects a clinical phenotype now recognized by its underlying genetic diagnosis, chromosome 22q11.2 deletion syndrome, which is associated with multisystem involvement and variable immune defects among patients. Updated genetic and molecular techniques now allow for earlier identification of immune defects and confirmatory diagnoses, in this disorder with life-long clinical issues.

https://ift.tt/2zcSXLT

Innovation in Food Challenge Tests for Food Allergy

Abstract

Purpose of Review

This review incorporates findings from studies of oral food challenges (OFC) over the last decade and highlights the latest innovations and understanding of the procedure.

Recent Findings

PRACTALL guidelines are widely used in OFC research, but there is still no international consensus on the OFC protocol in clinical practice. Guidelines for performing OFC in clinical practice have been updated to include oral food challenges for infants. There have been advances in predictive models for outcomes and severity of reaction during OFC that take into account multiple clinical data as well as newer laboratory modalities. Low-dose OFC and eliciting threshold dose determination are being examined for additional diagnostic and therapeutic use in the management of food allergy. Quality-of-life considerations have also been reviewed, as well as post-OFC assessment and care.

Summary

The OFC remains an important diagnostic tool in the management of food allergy and in clinical research. Advances in the field should improve safety and broaden the clinical applications of this essential procedure.

https://ift.tt/2SvqCJy

Letter to the Editor: In Response to Fang et al's Comment on “Diagnostic Accuracy of the McGill Thyroid Nodule Score in Pediatric Patients”

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2RjGQnM

Utility of systematic TSHR gene testing in adults with hyperthyroidism lacking overt autoimmunity and diffuse uptake on thyroid scintigraphy

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2Przqle

Primary aldosteronism is associated with decreased LDL and HDL particle concentrations and increased GlycA, a pro‐inflammatory glycoprotein biomarker

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2RqBQOt

Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Patient-Reported Outcomes from the ATMOS-1 and ATMOS-2 Phase III Randomized Controlled Trials

Abstract

Background

Glycopyrronium tosylate (GT) is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged ≥ 9 years. GT was evaluated for primary axillary hyperhidrosis in replicate, randomized, double-blind, vehicle-controlled, phase III trials. GT reduced sweating severity and production versus vehicle and was generally well tolerated.

Objective

Our objective was to evaluate patient-reported outcomes (PROs) from these trials.

Methods

Patients aged ≥ 9 years with primary axillary hyperhidrosis ≥ 6 months, gravimetrically measured sweat production ≥ 50 mg/5 min in each axilla, Axillary Sweating Daily Diary (ASDD) Item 2 severity score ≥ 4, and Hyperhidrosis Disease Severity Scale (HDSS) score ≥ 3 were randomized 2:1 to GT 3.75% or vehicle applied once daily to each axilla for 4 weeks. The 4-item ASDD, 6 Weekly Impact (WI) items, Patient Global Impression of Change (PGIC), HDSS, and Dermatology Life Quality Index (DLQI) were utilized.

Results

In the pooled population, 463 patients were randomized to GT and 234 to vehicle; 426 (92.0%) and 225 (96.2%) completed the trials. At baseline, most patients considered their axillary sweating to be at least moderate in severity, impact, and bothersomeness (ASDD items 2, 3, and 4, respectively). Improvement was substantially greater for GT than for vehicle at every study week, and, at week 4, ASDD scores improved from baseline by 62.6 versus 34.0% (severity), 65.5 versus 40.3% (impact), and 65.4 versus 39.0% (bothersomeness). Improvements favoring GT versus vehicle also occurred for WI items, PGIC, HDSS, and DLQI.

Conclusions

PRO results demonstrated that GT reduced the disease burden of primary axillary hyperhidrosis.

Trial registration

Clinicaltrials.gov; ATMOS-1 (NCT02530281), ATMOS-2 (NCT02530294).

https://ift.tt/2P0hmiu

Challenges and hurdles for patient safety in obstetric anesthesia in Japan

Abstract

The use of pain relief for labor has gained popularity in Japan. However, its acceptance is still low among laboring women: only 6.1% of Japanese parturients receive labor analgesia, in contrast with the United States, where approximately 70% receive labor analgesia. Unfortunately, several maternal deaths associated with labor analgesia have been reported in recent years in Japan and how to achieve safer obstetric care is a pressing concern. In this review, we focus on current approaches to labor analgesia in the United States as they compare to existing practices in Japan. We discuss challenges for the introduction and implementation of standard anesthesia practice into the Labor and Delivery Room (LDR; i.e., labor and delivery ward), aiming to secure safety for both mothers and fetus in every part of Japan in the near future.

https://ift.tt/2EQOwMV

Immune and Genetic Features of the Chromosome 22q11.2 Deletion (DiGeorge Syndrome)

Abstract

Purpose of Review

This review provides an update on the progress in identifying the range of immunological dysfunction seen in DiGeorge syndrome and on more recent diagnostic and treatment approaches.

Recent Findings

Summary

https://ift.tt/2zcSXLT

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τρίτη 30 Οκτωβρίου 2018

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