Head and Neck Diseases by Alexandros G.Sfakianakis: 10/25/18

Πέμπτη 25 Οκτωβρίου 2018

An update of the pathogenesis of frontal fibrosing alopecia: What does the current evidence tell us?

Australasian Journal of Dermatology, EarlyView.

https://ift.tt/2z4xXHh

Investigation and analysis of 1030 primary hair transplantation cases: a retrospective study

Abstract

Background

Hair transplantation has progressed since the introduction of the concept of follicular unit transplantation, a method that recognizes the follicular unit as the basic element of tissue to be transferred. It was aimed to estimate the area of donor scalp with the greatest probability contains the number of follicular units desired to transplant and to analyze the complications in all patients who underwent hair transplantation procedure.

Methods

A retrospective study was conducted in our clinic from January 2014 to January 2018.

Results

One thousand thirty hair restoration procedures were performed. Each patient was evaluated for age and gender in addition to the follicular unit density and postoperative complication rates. The mean age was 37.2 years. It was noted that the most common type of hair grouping was the 2-hair follicular unit grafts. The FU density ranged between 70 and 90 and the hair density ranged between 130 and 220 hair/cm². Postoperative frontal edema was the most common postoperative complication.

Conclusions

Data collected from this series can help to estimate the area of donor scalp with the greates probability of containing the number of follicular units desired to transplant.

Level of Evidence: Level IV, therapeutic study.

https://ift.tt/2SmUKXs

An update of the pathogenesis of frontal fibrosing alopecia: What does the current evidence tell us?

Australasian Journal of Dermatology, EarlyView.

https://ift.tt/2z4xXHh

Antiaging Effects of Urolithin A on Replicative Senescent Human Skin Fibroblasts

Rejuvenation Research, Ahead of Print.

https://ift.tt/2qbrqXh

Aloe-Emodin Ameliorates Renal Fibrosis Via Inhibiting PI3K/Akt/mTOR Signaling Pathway In Vivo and In Vitro

Rejuvenation Research, Ahead of Print.

https://ift.tt/2Rjd5DL

Use of calcium hydroxylapatite in the upper third of the face: Retrospective analysis of techniques, dilutions and adverse events

Journal of Cosmetic Dermatology, EarlyView.

https://ift.tt/2EIzQ2g

Use of calcium hydroxylapatite in the upper third of the face: Retrospective analysis of techniques, dilutions and adverse events

Journal of Cosmetic Dermatology, EarlyView.

https://ift.tt/2EIzQ2g

Adult bilateral idiopathic occlusion of foramina of Monro: is foraminoplasty really safe and effective?

Idiopathic bilateral occlusion of foramina of Monro is an extremely rare condition in adults and only few cases are reported. Currently, foraminoplasty is indicated as first-line treatment. We reported the case of a 52-year-old woman who presented with headache, instability and urinary incontinence. The imaging demonstrated bilateral occlusion of foramina of Monro and consequent biventricular hydrocephalus. A ventriculo-peritoneal shunt allowed to treat the hydrocephalus, but it was necessary to remove it for the appearance of peritonitis from salpingitis. Since the initial symptomatology reappeared, according to the literature, we performed an endoscopic foraminoplasty with septostomy. The patient immediately developed short-term memory impairment and subsequently we observed the hydrocephalus recurrence. The positioning of a ventriculo-atrial shunt allowed to improve the symptoms, but the memory remained impaired. In case of bilateral true stenosis of foramina of Monro, foraminoplasty may lead to severe memory impairment. Therefore, cerebrospinal fluid shunting should be considered as an effective and safer treatment.

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Prenatal diagnosis and management of fetal discordant alpha-thalassaemia in dichorionic diamniotic (DCDA) twins

A 29-year-old nulliparous woman with a dichorionic diamniotic (DCDA) twin pregnancy was referred to our hospital at 16 weeks' gestation for prenatal diagnosis. She was diagnosed of Haemoglobin H Constant Spring (Hb H CS; --^SEA/α^CSα) and her husband of alpha thalassemia-1 trait (--^SEA/αα). Detailed ultrasound showed that left twin had fetal anaemia and early signs of hydrops while the right one was normal. Both twins were female. Amniocentesis in each sac was performed for prenatal diagnosis of thalassemia after a proper counselling with the couple. DNA analysis confirmed that the left fetus was affected with haemoglobin Bart's hydrops fetalis (--^SEA/--^SEA) while the right one was alpha thalassemia-1 trait (--^SEA/αα). Selective feticide with intracardiac injection of KCl was successfully performed on the hydropic fetus. Identification of the affected fetus is crucial for selective termination. Family counselling about the procedure and complications is also necessary.

https://ift.tt/2yAJ3nP

Histologically confirmed case of complete atrioventricular block due to hepatocellular carcinoma

A 72-year-old man, who had been diagnosed as having hepatocellular carcinoma (HCC) with multiple extrahepatic metastasis, complained a general fatigue which appeared 2 weeks before admission. Because bradycardia was detected on physical examination, ECG was performed which revealed the complete atrioventricular (AV) block. We stopped Ca-blocker and β-blocker, but the bradycardia persisted. He was admitted to our hospital for an emergent pacemaker implantation. On admission, he complained dyspnoea. After the surgery, he died due to deterioration of heart failure. The autopsy revealed cardiac metastasis of HCC on AV node, so it was suspected that cardiac metastasis caused the AV block. We thought that the cause of his death was the exacerbation of heart failure associated with bradycardia. It was likely that complete AV block as a very rare complication caused by cardiac metastasis of HCC influenced the prognosis of this patient.

https://ift.tt/2O7U994

Umbilical cord anomalies: antenatal ultrasound findings and postnatal correlation

Umbilical cord anomalies are rare. The differential diagnosis for a cystic structure around the umbilical cord and its insertion include pseudocyst, omphalomesenteric duct cyst, haemangioma, omphalocele or anterior abdominal wall defects. Although cord anomalies can be detected through antenatal ultrasound scans (US), very often a definitive diagnosis cannot be made. This may affect the management of the infant at birth. In cases where antenatal US was not diagnostic, current evidence supports the use of MRI to help in making an accurate diagnosis. We report two cases of umbilical cord anomalies. The first case was diagnosed in antenatal US as an omphalocele, but was found to be an allantoic cyst with hamartoma on postnatal diagnosis. The second case was not detected on antenatal US, and was diagnosed postnatally as a small omphalocele with vitellointestinal duct remnants.

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Coronary artery vasospasm in a patient withChurg-Strauss syndrome

Patients with Churg-Strauss syndrome often suffer from unusual cardiac manifestations and sudden cardiac death. This differs from patients with other autoimmune disorders, who typically present with premature ischaemic heart disease. We report the case of a 56-year-old man with recurrent coronary vasospasm, including an inferoposterior ST-elevation myocardial infarction, complicated by bradycardic arrest. There was only minor coronary artery disease on coronary angiography. An elevated eosinophil count was noted. His medical history included allergic rhinitis with polyposis, adult-onset asthma and biopsy-proven eosinophilic oesophagitis. Review of his sinus biopsies demonstrated blood vessels with marked accumulation of eosinophils in extravascular areas. The patient, therefore, met the American College of Rheumatology criteria for Churg-Strauss syndrome. The patient was commenced on immunosuppression, with the return of the eosinophil count to within normal limits, and remains free of cardiovascular events over 24 months.

https://ift.tt/2O7U7xY

Not just another diplopia: neurocysticercosis in a postpartum woman

Description

A 23-year-old woman with a history of child birth 2 weeks back presented to the outpatient department with binocular diplopia and slight blurring of vision in both eyes (BE) for last 1 week. She also had four bouts of vomiting with associated nausea and hemicranial dull headache for last 3 days. The antenatal and immediate perinatal period was uneventful. Previous history as well as systemic history was not significant. The patient was afebrile. On systemic examination, neck stiffness could be elucidated. The blood pressure was recorded to be 124/74 mm Hg. Ocular examination revealed the visual acuity to be 20/40 in BE. There was restricted abduction of the right eye (figure 1) and diplopia charting revealed isolated sixth cranial nerve palsy. Pupillary reaction was brisk in BE with no evidence of relative afferent pupillary defect. Slit lamp evaluation of the anterior segment showed no abnormality. On fundus evaluation, bilateral disc oedema with ill-defined...

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Giant vesicle calculi leading to spontaneous bladder rupture and acute renal failure: an unusual presentation

Spontaneous rupture of the urinary bladder is extremely rare. We report a case of a 70-year-old man with spontaneous bladder rupture secondary to neglected giant vesicle calculi who presented as acute renal failure. The patient was stabilised with per-urethral catheterisation and extravesical drain placement. About 700 mL pus mixed with urine was drained through the per-urethral catheter and approximately 2000 mL of pus was drained through the extravesical drain. Cystolithotomy showed two large calculi which were removed.

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Acute aortic dissection: a missed diagnosis

A 60-year-old man with a history of indigestion and untreated hypertension presented with sudden-onset central chest pain which radiated to his back. Acute coronary syndrome was initially suspected but excluded in the emergency department before the patient was discharged. The pain subsequently abated to mild intermittent episodes and was misdiagnosed as indigestion. A week later the patient developed new shortness of breath and 'flu-like' symptoms with a positive d-dimer test. CT angiography revealed a Stanford type B aortic dissection which was causing hypoperfusion of the right kidney, resulting in an acute kidney injury. Due to uncontrolled hypertension despite rigorous antihypertensive medication and his failing renal function, the patient underwent endovascular repair and made a good recovery postoperatively.

https://ift.tt/2yA30ev

Proximal humerus deformity, in a four-limb amputee following meningococcal septicaemia

We present a challenging case of proximal humerus varus deformity in a four-limb amputee, caused by growth arrest from meningococcal septicaemia. The deformity resulted in a loss of function for our patient with inhibition of activities of daily living, requiring corrective osteotomy to help improve the range of motion of the shoulder. We describe in detail the management of our patient, highlight the importance of the orthopaedic manifestations of meningococcal septicaemia, and demonstrate the importance of monitoring potential deformities from growth arrest in these patients.

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Tuberous sclerosis complex: a clinical case with multiple ophthalmological manifestations

The tuberous sclerosis complex is a rare disease, with autosomal dominant transmission, with multisystemic involvement including ophthalmologic. Retinal hamartomas and retinal achromic patch are the most frequent ocular findings. Other ophthalmic signs and symptoms are relatively rare in this disease.

We describe the case of a young woman with tuberous sclerosis who presented with horizontal binocular diplopia and decreased visual acuity without complaints of nausea, vomiting or headache. She had right abducens nerve palsy, pale oedema of both optic discs and retinal hamartomas. An obstructive hydrocephalus caused by an intraventricular expansive lesion was identified in brain CT.

Observation by the ophthalmologist is indicated in all confirmed or suspected cases of tuberous sclerosis to aid in clinical diagnosis, monitoring of retinal hamartomas or identification of poorly symptomatic papilloedema.

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Chest pain following permanent pacemaker insertion... a case of pneumopericardium due to atrial lead perforation

Permanent pacemaker (PPM) implantation is an increasingly common procedure with complication rate estimated between 3% and 6%. Cardiac perforation by pacemaker lead(s) is rare, but a previous study has shown that it is probably an underdiagnosed complication. We are presenting a case of a patient who presented 5 days after PPM insertion with new-onset pleuritic chest pain. She had a normal chest X-ray (CXR), and acceptable pacing checks. However, a CT scan of the chest showed pneumopericardium and pneumothorax secondary to atrial lead perforation. The pain only settled by replacing the atrial lead. A repeat chest CT scan a few months later showed complete resolution of the pneumopericardium and pneumothorax. We believe that cardiac perforation can be easily missed if associated with normal CXR and acceptable pacing parameters. Unexplained chest pain following PPM insertion might be the only clue for such complication, although it might not always be present.

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Solitary fibrous tumour of caecum wall: an unlikely cause of low gastrointestinal haemorrhage

Solitary fibrous tumour (SFT), previously denominated as haemangiopericytoma, is a rare, spindle cell neoplasm that was first described in the thoracic pleura. It is now known that this tumour may develop from almost any anatomic location. We report a case of SFT, in a 65-year-old man, which was located in the muscularis propria layer of the caecum with involvement of the serosa and the ileocecal appendix, location never described in the literature, and with an uncommon clinical presentation of hematochezia. A radical right hemicolectomy was performed, and the patient was asymptomatic without evidence of metastasis or relapse after 6 months of follow-up.

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Neck carbuncle associated with methicillin-susceptible Staphylococcus aureus bacteraemia

Description

A 66-year-old man presented with a 14-day history of painful posterior neck swelling and fever for a week prior to presentation. A restricted neck movements was noted over the last 3 days. Generally, he had a fever of 37.5°C and tachycardia at 121 bpm, whereas the other vital signs were normal. Local physical examination showed large posterior neck swelling with erythema and multiple sinuses discharging pus.

A neck carbuncle was diagnosed (figure 1).1 2 Skin eruptions were noted also on the lower extremities and gluteal region.

Figure 1

Physical examination. (a) A pustule in posterior neck which is surrounded by an extensive erythematous swelling (white dotted circle). (b) The pustules that have the same features were seen at lower extremity and gluteal region.

Laboratory evaluation showed a haemoglobin level of 14.3 g/dL, leucocyte count of 38 800x109/L, sodium of 132 mmol/L, creatinine of...

https://ift.tt/2O7U19A

Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness

Abstract

Background

Non-thyroidal illness (NTI) is frequent in hospitalized patients. Its recovery is characterized by a raise in TSH levels. However, the clinical significance of high TSH levels at admission in hospitalized elderly patients with NTI remains uncertain.

Aim

To explore the relevance of baseline TSH evaluation in hospitalized elderly patients with NTI.

Methods

We examined the participants with NTI (n = 123) from our previous study (Sforza, 2017). NTI was defined as: low T3 (< 80 ng/dL) and normal or low total T4 in the presence of TSH values between 0.1 and 6.0 mU/L. Thyroid function tests were performed on day 1 and day 8 of the hospital stay. Positive TSH changes (+ ΔTSH) were considered when the day-8 TSH value increased more than the reference change value for TSH (+ 78%). Multiple logistic regression was used to evaluate the independent association of baseline TSH, sex, clinical comorbidities (by ACE-27) and medications with + ΔTSH.

Results

Out of 123 patients (77 ± 8 years, 52% female), 34 showed a + ΔTSH. These patients had a lower TSH at admission (p < 0.001) and intra-hospital mortality (p = 0.003) than the others. In multiple logistic regression, TSH > 2.11 mU/L at baseline was associated with reduced odds to show + ΔTSH [odds ratio (95 CI) 0.29 (0.11–0.75); p = 0.011] in a model adjusted by age, sex and ACE-27.

Discussion

Inappropriately higher TSH levels at admission in hospitalized elderly patients were associated with a reduced ability to raise their TSH levels later on. The present results confront the idea that TSH levels at admission are irrelevant in this clinical context.

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Multiple yellow nodules in a 13‐year‐old girl

Clinical and Experimental Dermatology, EarlyView.

https://ift.tt/2OMP2QG

Painful papule on the right arm of a woman

Clinical and Experimental Dermatology, EarlyView.

https://ift.tt/2O7mYCj

Human papilloma virus infection in the healing thermal‐burn wound in a child

Clinical and Experimental Dermatology, EarlyView.

https://ift.tt/2OPRtlH

Multiple yellow nodules in a 13‐year‐old girl

Clinical and Experimental Dermatology, EarlyView.

https://ift.tt/2OMP2QG

Painful papule on the right arm of a woman

Clinical and Experimental Dermatology, EarlyView.

https://ift.tt/2O7mYCj

Human papilloma virus infection in the healing thermal‐burn wound in a child

Clinical and Experimental Dermatology, EarlyView.

https://ift.tt/2OPRtlH

Phase II Trial of 5‐Fluorouracil, Docetaxel, and Nedaplatin (UDON) Combination Therapy for Recurrent or Metastatic Esophageal Cancer

Lessons Learned. The 5‐fluorouracil, docetaxel, and nedaplatin (UDON) regimen was well tolerated and showed promising antitumor activity in terms of both objective response rate and survival for patients with advanced or recurrent esophageal squamous cell carcinoma in the first‐line setting.UDON may be an optimal treatment option for patients with advanced esophageal cancer who are unfit for docetaxel, cisplatin, and 5‐fluorouracil regimens.The high response rate as well as the rapid and marked tumor shrinkage associated with UDON suggest that further evaluation of this regimen in the neoadjuvant setting is warranted.Background.A phase II study was performed to evaluate the efficacy and safety of 5‐fluorouracil (5‐FU), docetaxel, and nedaplatin (UDON) combination therapy for untreated recurrent or metastatic esophageal cancer.Methods.Patients received intravenous nedaplatin (90 mg/m2) on day 1, docetaxel (35 mg/m2) on days 1 and 15, and 5‐fluorouracil (800 mg/m2) on days 1–5 of a 4‐week cycle. The primary endpoint was response rate, with secondary endpoints including overall survival (OS), progression‐free survival (PFS), dysphagia score, and adverse events.Results.Between March 2015 and July 2017, 23 patients were enrolled. Of 22 evaluable patients, 16 and 4 individuals experienced a partial response and stable disease, respectively, yielding a response rate of 72.7% (95% confidence interval [CI], 49.8%–89.3%) and disease control rate of 90.9% (95% CI, 70.8%–98.9%). Median OS and PFS were 11.2 months (95% CI, 9.1 months to not reached) and 6.0 months (95% CI, 2.5–10.6 months), respectively. Eleven (64.7%) of the 17 patients with a primary lesion showed amelioration of dysphagia after treatment. Frequent adverse events of grade 3 or 4 included neutropenia (87.0%) and leukopenia (39.1%). Febrile neutropenia was observed in two patients (8.7%).Conclusion.This phase II study demonstrated promising antitumor activity and good tolerability of UDON.

https://ift.tt/2PpctyZ

Dead or alive: how the immune system detects microbial viability

Matteo Ugolini | Leif E Sander

https://ift.tt/2PVsLgd

Management of Squamous Cell Carcinoma Involving the Temporal Bone

Abstract

Purpose of Review

To examine contemporary management of squamous cell carcinoma (SCC) involving the temporal bone.

Recent Findings

The modified Pittsburgh criteria have gained acceptance by many institutions for staging, planning treatment and comparing outcomes. Often primary SCC as well as secondary cutaneous SCC involving the temporal bone can be managed in a similar fashion.

Summary

T1 tumours should undergo lateral temporal bone resection (LTBR) due to the higher risk of positive margins and recurrence rates with lesser surgical procedures. T2 tumours require LTBR and superficial parotidectomy. T3 and T4 tumours often require a subtotal resection of the temporal bone (STBR), parotidectomy and cutaneous soft tissues as an en bloc excision. Advanced lesions are associated with a diminished survival especially if margins are involved. Patient outcomes are improved by a combination of surgery and postoperative radiotherapy. Preoperative imaging with high resolution CT and MRI is useful, particularly if there is evidence of large nerve perineural spread and nodal disease.

https://ift.tt/2SjOKPy

Richard Studley Farr, MD

During the early 1960s, I was a postdoctoral fellow under the mentorship of David W. Talmage, MD. The laboratory at the University of Colorado Health Sciences Center was a crossroads for visiting allergists and immunologists from all over the world. Dr. Talmage would arrange for the fellows to meet one-on-one with many of the visitors. For some visitors, a suggestion was made to avoid discussing any work that was not well along the path to publication. When Dr. Richard Farr came to visit, the suggestion was, "you should get Dick Farr's thoughts about this." Very worthwhile advice indeed.

https://ift.tt/2CIdiMO

More Press Coverage from the 88th Annual Meeting of the ATA

From endocrineweb

Combination Immunotherapies to Treat Advanced Thyroid Cancers

Diet for Thyroid Disease: What You Need to Know

Matching Expectations and Guidelines to Treatment-Worthy Thyroid Cancers

Liver Failure: A Turning Point in Graves' Disease Treatment

The post More Press Coverage from the 88th Annual Meeting of the ATA appeared first on American Thyroid Association.

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High Thyrotropin Is Associated with Reduced Hippocampal Volume in a Population-Based Study from Germany

Thyroid, Ahead of Print.

https://ift.tt/2OLvdJs

More Press Coverage from the 88th Annual Meeting of the ATA

From endocrineweb

Combination Immunotherapies to Treat Advanced Thyroid Cancers

Diet for Thyroid Disease: What You Need to Know

Matching Expectations and Guidelines to Treatment-Worthy Thyroid Cancers

Liver Failure: A Turning Point in Graves' Disease Treatment

The post More Press Coverage from the 88th Annual Meeting of the ATA appeared first on American Thyroid Association.

https://ift.tt/2RhD8v8

Erosive pustular dermatosis of the scalp: a neutrophilic folliculitis within the spectrum of neutrophilic dermatoses. A clinicopathologic study of thirty cases

Histopathology of primary lesion of erosive pustular dermatosis of the scalp has not been characterized. Biopsy of intact follicular pustules shows spongiotic vesiculo-pustules affecting the follicular infundibula. Erosive pustular dermatosis of the scalp is a neutrophilic superficial folliculitis, with some clinicopathologic similarities with other pathergic neutrophilic dermatoses, such as pyoderma gangrenosum.

https://ift.tt/2PjGMao

Development and Implementation of an Order Set to Improve Value of Care for Patients with Severe Stasis Dermatitis

https://ift.tt/2Jhn1dZ

Dysplastic Nevi: Monitoring and Management

Is it safe to observe moderately dysplastic nevi with positive histologic margins, or is the risk for cutaneous melanoma too high?
Medscape Dermatology

https://ift.tt/2yZ1vWA

Comparison of treatment plans for a high-field MRI-linac and a conventional linac for esophageal cancer

Abstract

Purpose

To compare radiotherapy treatments plans in esophageal cancer calculated for a high-field magnetic resonance imaging (MRI)-linac with plans for a conventional linac.

Materials and methods

Ten patients with esophageal squamous cell carcinomas were re-planned retrospectively using the research version of Monaco (V 5.19.03, Elekta AB, Stockholm, Sweden). Intensity modulated radiotherapy (IMRT) plans with a nine-field step-and-shoot technique and two-arc volumetric modulated arc therapy (VMAT) plans were created for the Elekta MRI-linac and a conventional linac, respectively. The prescribed dose was 60 Gy to the primary tumor (PTV₆₀) and 50 Gy to elective volumes (PTV₅₀). Plans were optimized for optimal coverage of the 60 Gy volume and compared using dose–volume histogram parameters.

Results

All calculated treatment plans met predefined criteria for target volume coverage and organs at risk dose both for MRI-linac and conventional linac. Plans for the MRI-linac had a lower number of segments and monitor units. No significant differences between both plans were seen in terms of V_20Gy of the lungs and V_40Gy of the heart with slightly higher mean doses to the heart (14.0 Gy vs. 12.5 Gy) and lungs (12.8 Gy vs. 12.2 Gy).

Conclusion

Applying conventional target volume and margin concepts as well as dose-fractionation prescription reveals clinically acceptable dose distributions using hybrid MRI-linac in its current configuration compared to standard IMRT/VMAT. This represents an important prerequisite for future studies to investigate the clinical benefit of MRI-guided radiotherapy exploiting the conceptional advantages such as reduced margins, plan adaptation and biological individualization and hypofractionation.

https://ift.tt/2z2tQvu

MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence

mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results ach...

https://ift.tt/2O6oaWA

Use-Dependent Plasticity in Human Primary Motor Hand Area: Synergistic Interplay Between Training and Immobilization

Abstract

Training and immobilization are powerful drivers of use-dependent plasticity in human primary motor hand area (M1_HAND). In young right-handed volunteers, corticomotor representations of the left first dorsal interosseus and abductor digiti minimi muscles were mapped with neuronavigated transcranial magnetic stimulation (TMS) to elucidate how finger-specific training and immobilization interact within M1_HAND. A first group of volunteers trained to track a moving target on a smartphone with the left index or little finger for one week. Linear sulcus shape-informed TMS mapping revealed that the tracking skill acquired with the trained finger was transferred to the nontrained finger of the same hand. The cortical representations of the trained and nontrained finger muscle converged in proportion with skill transfer. In a second group, the index or little finger were immobilized for one week. Immobilization alone attenuated the corticomotor representation and pre-existing tracking skill of the immobilized finger. In a third group, the detrimental effects of finger immobilization were blocked by concurrent training of the nonimmobilized finger. Conversely, immobilization of the nontrained fingers accelerated learning in the adjacent trained finger during the first 2 days of training. Together, the results provide novel insight into use-dependent cortical plasticity, revealing synergistic rather than competitive interaction patterns within M1_HAND.

https://ift.tt/2RdtSYU

Neural Dynamics of Reward-Induced Response Activation and Inhibition

Abstract

Reward-predictive stimuli can increase an automatic response tendency, which needs to be counteracted by effortful response inhibition when this tendency is inappropriate for the current task. Here we investigated how the human brain implements this dynamic process by adopting a reward-modulated Simon task while acquiring EEG and fMRI data in separate sessions. In the Simon task, a lateral target stimulus triggers an automatic response tendency of the spatially corresponding hand, which needs to be overcome if the activated hand is opposite to what the task requires, thereby delaying the response. We associated high or low reward with different targets, the location of which could be congruent or incongruent with the correct response hand. High-reward targets elicited larger Simon effects than low-reward targets, suggesting an increase in the automatic response tendency induced by the stimulus location. This tendency was accompanied by modulations of the lateralized readiness potential over the motor cortex, and was inhibited soon after if the high-reward targets were incongruent with the correct response hand. Moreover, this process was accompanied by enhanced theta oscillations in medial frontal cortex and enhanced activity in a frontobasal ganglia network. With dynamical causal modeling, we further demonstrated that the connection from presupplementary motor area (pre-SMA) to right inferior frontal cortex (rIFC) played a crucial role in modulating the reward-modulated response inhibition. Our results support a dynamic neural model of reward-induced response activation and inhibition, and shed light on the neural communication between reward and cognitive control in generating adaptive behaviors.

https://ift.tt/2ONov5Z

Cultural variation in the gray matter volume of the prefrontal cortex is moderated by the dopamine D4 receptor gene (DRD4)

Abstract

Recent evidence suggests a systematic cultural difference in the volume/thickness of prefrontal regions of the brain. However, origins of this difference remain unclear. Here, we addressed this gap by adopting a unique genetic approach. People who carry the 7- or 2-repeat (7/2-R) allele of the dopamine D4 receptor gene (DRD4) are more sensitive to environmental influences, including cultural influences. Therefore, if the difference in brain structure is due to cultural influences, it should be moderated by DRD4. We recruited 132 young adults (both European Americans and Asian-born East Asians). Voxel-based morphometry showed that gray matter (GM) volume of the medial prefrontal cortex and the orbitofrontal cortex was significantly greater among European Americans than among East Asians. Moreover, the difference in GM volume was significantly more pronounced among carriers of the 7/2-R allele of DRD4 than among non-carriers. This pattern was robust in an alternative measure assessing cortical thickness. A further exploratory analysis showed that among East Asian carriers, the number of years spent in the U.S. predicted increased GM volume in the orbitofrontal cortex. The present evidence is consistent with a view that culture shapes the brain by mobilizing epigenetic pathways that are gradually established through socialization and enculturation.

https://ift.tt/2RgR7kJ

Transient and Sustained Control Mechanisms Supporting Novel Instructed Behavior

Abstract

The success of humans in novel environments is partially supported by our ability to implement new task procedures via instructions. This complex skill has been associated with the activity of control-related brain areas. Current models link fronto-parietal and cingulo-opercular networks with transient and sustained modes of cognitive control, based on observations during repetitive task settings or rest. The current study extends this dual model to novel instructed tasks. We employed a mixed design and an instruction-following task to extract phasic and tonic brain signals associated with the encoding and implementation of novel verbal rules. We also performed a representation similarity analysis to capture consistency in task-set encoding within trial epochs. Our findings show that both networks are involved while following novel instructions: transiently, during the implementation of the instruction, and in a sustained fashion, across novel trials blocks. Moreover, the multivariate results showed that task representations in the cingulo-opercular network were more stable than in the fronto-parietal one. Our data extend the dual model of cognitive control to novel demanding situations, highlighting the high flexibility of control-related regions in adopting different temporal profiles.

https://ift.tt/2OOAhgg

Visual and Vestibular Selectivity for Self-Motion in Macaque Posterior Parietal Area 7a

Abstract

We examined the responses of neurons in posterior parietal area 7a to passive rotational and translational self-motion stimuli, while systematically varying the speed of visually simulated (optic flow cues) or actual (vestibular cues) self-motion. Contrary to a general belief that responses in area 7a are predominantly visual, we found evidence for a vestibular dominance in self-motion processing. Only a small fraction of neurons showed multisensory convergence of visual/vestibular and linear/angular self-motion cues. These findings suggest possibly independent neuronal population codes for visual versus vestibular and linear versus angular self-motion. Neural responses scaled with self-motion magnitude (i.e., speed) but temporal dynamics were diverse across the population. Analyses of laminar recordings showed a strong distance-dependent decrease for correlations in stimulus-induced (signal correlation) and stimulus-independent (noise correlation) components of spike-count variability, supporting the notion that neurons are spatially clustered with respect to their sensory representation of motion. Single-unit and multiunit response patterns were also correlated, but no other systematic dependencies on cortical layers or columns were observed. These findings describe a likely independent multimodal neural code for linear and angular self-motion in a posterior parietal area of the macaque brain that is connected to the hippocampal formation.

https://ift.tt/2Res7dE

The Corticospinal Discrepancy: Where are all the Slow Pyramidal Tract Neurons?

Abstract

This feature article focuses on the discrepancy between the distribution of axon diameters within the primate corticospinal tract, determined neuroanatomically, and the distribution of axonal conduction velocities within the same tract, determined electrophysiologically. We point out the importance of resolving this discrepancy for a complete understanding of corticospinal functions, and discuss the various explanations for the mismatch between anatomy and physiology.

https://ift.tt/2ONKMR8

Precision Inhibitory Stimulation of Individual-Specific Cortical Hubs Disrupts Information Processing in Humans

Abstract

Noninvasive brain stimulation (NIBS) is a promising treatment for psychiatric and neurologic conditions, but outcomes are variable across treated individuals. In principle, precise targeting of individual-specific features of functional brain networks could improve the efficacy of NIBS interventions. Network theory predicts that the role of a node in a network can be inferred from its connections; as such, we hypothesized that targeting individual-specific "hub" brain areas with NIBS should impact cognition more than nonhub brain areas. Here, we first demonstrate that the spatial positioning of hubs is variable across individuals but reproducible within individuals upon repeated imaging. We then tested our hypothesis in healthy individuals using a prospective, within-subject, double-blind design. Inhibition of a hub with continuous theta burst stimulation disrupted information processing during working-memory more than inhibition of a nonhub area, despite targets being separated by only a few centimeters on the right middle frontal gyrus of each subject. Based upon these findings, we conclude that individual-specific brain network features are functionally relevant and could leveraged as stimulation sites in future NIBS interventions.

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Is Human Auditory Cortex Organization Compatible With the Monkey Model? Contrary Evidence From Ultra-High-Field Functional and Structural MRI

Abstract

It is commonly assumed that the human auditory cortex is organized similarly to that of macaque monkeys, where the primary region, or "core," is elongated parallel to the tonotopic axis (main direction of tonotopic gradients), and subdivided across this axis into up to 3 distinct areas (A1, R, and RT), with separate, mirror-symmetric tonotopic gradients. This assumption, however, has not been tested until now. Here, we used high-resolution ultra-high-field (7 T) magnetic resonance imaging (MRI) to delineate the human core and map tonotopy in 24 individual hemispheres. In each hemisphere, we assessed tonotopic gradients using principled, quantitative analysis methods, and delineated the core using 2 independent (functional and structural) MRI criteria. Our results indicate that, contrary to macaques, the human core is elongated perpendicular rather than parallel to the main tonotopic axis, and that this axis contains no more than 2 mirror-reversed gradients within the core region. Previously suggested homologies between these gradients and areas A1 and R in macaques were not supported. Our findings suggest fundamental differences in auditory cortex organization between humans and macaques.

https://ift.tt/2OQfIA7

Continuity and Discontinuity in Human Cortical Development and Change From Embryonic Stages to Old Age

Abstract

The human cerebral cortex is highly regionalized, and this feature emerges from morphometric gradients in the cerebral vesicles during embryonic development. We tested if this principle of regionalization could be traced from the embryonic development to the human life span. Data-driven fuzzy clustering was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) (n = 301, 4–12 years). The principal divide for the developmental SA clusters extended from the inferior–posterior to the superior–anterior cortex, corresponding to the major embryonic morphometric anterior–posterior (AP) gradient. Embryonic factors showing a clear AP gradient were identified, and we found significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT clusters showed distinguishable life span trajectories in a larger longitudinal dataset (4–88 years, 1633 observations), and the SA and CT clusters showed differential relationships to cognitive functions. This means that regions that developed together in childhood also changed together throughout life, demonstrating continuity in regionalization of cortical changes. The AP divide in SA development also characterized genetic patterning obtained in an adult twin sample. In conclusion, the development of cortical regionalization is a continuous process from the embryonic stage throughout life.

https://ift.tt/2R9VtKc

High-Expanding Regions in Primate Cortical Brain Evolution Support Supramodal Cognitive Flexibility

Abstract

Primate cortical evolution has been characterized by massive and disproportionate expansion of a set of specific regions in the neocortex. The associated increase in neocortical neurons comes with a high metabolic cost, thus the functions served by these regions must have conferred significant evolutionary advantage. In the present series of analyses, we show that evolutionary high-expanding cortex – as estimated from patterns of surface growth from several primate species – shares functional connections with different brain networks in a context-dependent manner. Specifically, we demonstrate that high-expanding cortex is characterized by high internetwork functional connectivity; is recruited flexibly over many different cognitive tasks; and changes its functional coupling pattern between rest and a multimodal task-state. The capacity of high-expanding cortex to connect flexibly with various specialized brain networks depending on particular cognitive requirements suggests that its selective growth and sustainment in evolution may have been linked to an involvement in supramodal cognition. In accordance with an evolutionary-developmental view, we find that this observed ability of high-expanding regions – to flexibly modulate functional connections as a function of cognitive state – emerges gradually through childhood, with a prolonged developmental trajectory plateauing in young adulthood.

https://ift.tt/2ORFgwP

Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells

Abstract

Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic "universal" cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products. In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing.

https://ift.tt/2D47nm4

Sex differences in autoimmune disorders of the central nervous system

Abstract

Stronger adaptive immune responses in females can be observed in different mammals, resulting in better control of infections compared to males. However, this presumably evolutionary difference likely also drives higher incidence of autoimmune diseases observed in humans. Here, we summarize sex differences in the most common autoimmune diseases of the central nervous system (CNS) and discuss recent advances in the understanding of possible underlying immunological and CNS intrinsic mechanisms. In multiple sclerosis (MS), the most common inflammatory disease of the CNS, but also in rarer conditions, such as neuromyelitis optica spectrum disorders (NMOSD) or neuronal autoantibody–mediated autoimmune encephalitis (AE), sex is one of the top risk factors, with women being more often affected than men. Immunological mechanisms driving the sex bias in autoimmune CNS diseases are complex and include hormonal as well as genetic and epigenetic effects, which could also be exerted indirectly via modulation of the microbiome. Furthermore, CNS intrinsic differences could underlie the sex bias in autoimmunity by differential responses to injury. The strong effects of sex on incidence and possibly also activity and progression of autoimmune CNS disorders suggest that treatments need to be tailored to each sex to optimize efficacy. To date, however, due to a lack of systematic studies on treatment responses in males versus females, evidence in this area is still sparse. We argue that studies taking sex differences into account could pave the way for sex-specific and therefore personalized treatment.

https://ift.tt/2EIvF6I

Sexual dimorphism in solid and hematological malignancies

Abstract

Cancer represents a leading cause of death with continuously increasing incidence worldwide. Many solid cancer types in non-reproductive organs are significantly more frequent and deadly in males compared to females. This sex-biased difference is also present in hematologic malignancies. In this review, we present an overview about sex differences in cancer with a focus on leukemia. We discuss mechanisms potentially underlying the observed sex-biased imbalance in cancer incidence and outcome including sex hormones, sex chromosomes, and immune responses. Besides affecting the pathobiology of cancers, sex differences can also influence drug responses, most notably those to immune checkpoint blockers. Therefore, sex should become a relevant factor in clinical trial design in order to avoid over- or under-treatment of one sex.

https://ift.tt/2D3J5IV

Sex differences in tuberculosis

Abstract

Tuberculosis is the most prevalent bacterial infectious disease in humans and the leading cause of death from a single infectious agent, ranking above HIV/AIDS. The causative agent, Mycobacterium tuberculosis, is carried by an estimated two billion people globally and claims more than 1.5 million lives each year. Tuberculosis rates are significantly higher in men than in women, reflected by a male-to-female ratio for worldwide case notifications of 1.7. This phenomenon is not new and has been reported in various countries and settings over the last century. However, the reasons for the observed gender bias are not clear, potentially highly complex and discussed controversially in the literature. Both gender- (referring to sociocultural roles and behavior) and sex-related factors (referring to biological aspects) likely contribute to higher tuberculosis rates in men and will be discussed.

https://ift.tt/2EIvCb2

The effect of maxillary sinus antrostomy size on the sinus microbiome

International Forum of Allergy &Rhinology, EarlyView.

https://ift.tt/2CERIIO

The role of galactomannan Aspergillus antigen in diagnosing acute invasive fungal sinusitis

International Forum of Allergy &Rhinology, EarlyView.

https://ift.tt/2q9cLM2

Exposure to 3‐methyl‐4‐nitrophenol (MNP) facilitates development of intestinal allergy

Allergy, Volume 0, Issue ja, -Not available-.

https://ift.tt/2yz77rs

Glucocorticoid activation by 11β‐hydroxysteroid dehydrogenase enzymes in relation to inflammation and glycaemic control in chronic kidney disease: a cross‐sectional study

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

https://ift.tt/2PoBeeO

Clinical practice update on testosterone therapy for male hypogonadism: contrasting perspectives to optimise care

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

https://ift.tt/2EMKW6J

Paediatric‐onset and adult‐onset Graves’ disease share multiple genetic risk factors

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

https://ift.tt/2PpiknW

Immunosuppressive therapy of autoimmune hypoparathyroidism in a patient with activating autoantibodies against the calcium‐sensing receptor

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

https://ift.tt/2EJHOs7

miR-21 expression analysis in budding colon cancer cells by confocal slide scanning microscopy

Abstract

MicroRNA-21 (miR-21) expression in stromal fibroblastic cells in colorectal cancer is well-documented, whereas miR-21 expression in tumor budding cells (TBCs) is poorly described. TBCs are locally invasive carcinoma cells with increased metastatic properties and characteristics of epithelial to mesenchymal transition. This study was conducted to better characterize the expression of miR-21 in TBCs. First, chromogenic miR-21 in situ hybridization (ISH) staining was performed in 58 colon adenocarcinomas with evident TBCs. Then, to obtain unambiguous identification of miR-21 in the TBCs, twenty cases were selected for an additional multiplex fluorescence analysis combining miR-21 ISH with cytokeratin and laminin-5γ2 immunofluorescence. Employing confocal slide scanning microscopy, comprehensive digital images of the invasive front (10–40 mm²) were obtained from 16 of the 20 cases, and miR-21 expression was evaluated in cytokeratin-positive TBCs. The high resolution of the confocal digital slide images allowed a detailed examination of the confocal stacks of the multiplex-stained tissue sections. The cases with the highest fraction of miR-21 positive TBCs were all stage III cancers defined by the presence of regional lymph node metastasis. Some of the miR-21 positive TBCs were also laminin-5γ2 positive. The confocal image stacks also revealed that some TBCs were actually directly connected to malignant glands. In conclusion, miR-21 expression was unambiguously identified in TBCs by evaluation of digital slides obtained by confocal slide scanning microscopy. In addition, the digital confocal slides provided a more detailed understanding of local cancer cell invasion by allowing evaluation of the cell structures in three dimensions.

https://ift.tt/2D5sl3Z

Audiological and clinical outcomes of a transcutaneous bone conduction hearing implant: 6‐month results from a multicenter study

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

https://ift.tt/2PkPnK0

Pacritinib in Patients With Myelofibrosis

To the Editor In the phase 3 PERSIST-2 study reported by Mascarenhas et al, a Janus kinase 2 (JAK2) inhibitor, pacritinib, was more effective than best available therapy (BAT), including a JAK1 and JAK2 inhibitor, ruxolitinib, for reducing the size of the spleen and subjective symptoms in patients with myelofibrosis who had intermediate- or high-risk disease and moderate to severe thrombocytopenia. We have several concerns about this randomized clinical trial.

https://ift.tt/2Jg7ETg

Pacritinib in Patients with Myelofibrosis—Reply

In Reply We thank Dr Suzuki and colleagues for their comments regarding our article. Their assumption regarding reduced incidence of herpes zoster infection in patients treated with pacritinib relative to ruxolitinib or other Janus kinase 1/2 inhibitors is borne out by the clinical data: the incidence of herpes zoster infection in the PERSIST-2 trial was 0%, 1%, and 1% in the pacritinib 200 mg twice daily, 400 mg once daily, and best available therapy arms, respectively (unpublished data, CTI BioPharma Corp, clinical study report for PERSIST-2 trial, November 2016). Although some patients in the best available therapy arm received ruxolitinib, their exposure was predominantly low dose and of short duration owing to the high crossover rate to pacritinib after 24 weeks. In the overall clinical trial experience with pacritinib in patients with myelofibrosis (n = 692), the incidence of herpes zoster infection was 0.6% with median pacritinib treatment of 8.3 months (maximum treatment, 3.3 years). The incidence of other opportunistic infections has been similarly low.

https://ift.tt/2PkAIyf

Redefining the Role of Prophylactic Cranial Irradiation in the Era of Active Surveillance in SCLC

This Viewpoint discusses the role of prophylactic cranial irradiation in small cell lung cancer in the current setting of active surveillance via magnetic resonance imaging.

https://ift.tt/2Jg7Ce6

Bevacizumab vs Cetuximab Plus Chemotherapy in KRAS Wild-Type mCRC

This open-label, randomized phase 2 trial evaluates progression-free survival with chemotherapy plus bevacizumab vs cetuximab among patients with progression of metastatic colorectal cancer (mCRC) after bevacizumab plus chemotherapy.

https://ift.tt/2PkAGq7

Surviving Cancer in the Midst of a Treatment Revolution: Hope and Delusion

In this article, the author discusses his struggles with hope and delusion in his personal experience with renal cell carcinoma.

https://ift.tt/2Jg7AD0

Nivolumab Monotherapy in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma

This follow-up of a randomized phase 3 trial compares the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma.

https://ift.tt/2PouJZl

The immunobiology of female predominance in primary biliary cholangitis

Publication date: Available online 25 October 2018

Source: Journal of Autoimmunity

Author(s): Alessio Gerussi, Laura Cristoferi, Marco Carbone, Rosanna Asselta, Pietro Invernizzi

Abstract

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a striking female preponderance. The mechanisms behind this predominance are still to be elucidated, although multiple theories have been postulated and investigated. Among the proposed involved factors, sex hormones have been the first to be studied, but unfortunately data have been inconclusive or conflicting. Similarly, fetal microchimerism has received a huge attention in the past, but data in PBC have been unsatisfactory especially if compared to other autoimmune diseases like systemic lupus erythematosus. Studies focused on genetic factors have generated more intriguing and robust data, reporting a few abnormalities on the X chromosome in PBC patients. However, these data are able to explain only a part of the phenotypic variability attributed to the genetic component, and most importantly, need to be validated in larger series. More recently, a novel mice model of PBC, characterised by a constitutive expression of Interferon-γ (IFN-γ), has been developed and it is notable for being the first one with female predominance. At the same time, there has been a wide interest in the role of microbiome in health and disease, as well as in epigenetics, which have tried to explain differences in biological phenotypes not covered by genetics. The aim of this review is to outline established knowledge on the topic and try to provide novel perspectives on the potential future applications of newer techniques addressing microbiome and epigenome, in order to further understand the biology of sex divergence in PBC.

https://ift.tt/2OO5j7P

Primary central nervous system vasculitis mimicking brain tumor: Comprehensive analysis of 13 cases from a single institutional cohort of 191 cases

Publication date: Available online 24 October 2018

Source: Journal of Autoimmunity

Author(s): Carlo Salvarani, Robert D. Brown, Teresa J.H. Christianson, John Huston, Jonathan M. Morris, Caterina Giannini, Gene G. Hunder

Abstract

Objective

To describe the clinical, laboratory, and imaging features and course of patients with primary central nervous system vasculitis (PCNSV) presenting with an intracranial tumor-like mass (TLM).

Methods

We retrospectively studied a cohort of 191 consecutive patients with PCNSV seen at the Mayo Clinic, Rochester, MN over a 35-year period (1982–2017). 13/191 patients presented with a TLM. We compared the findings in these 13 patients with those from the 178 without this presentation.

Results

In 13 of 191 (6.8%) patients with TLM the diagnosis of PCNSV was established by cerebral biopsy. Granulomatous vasculitis was found in 11/13 patients, accompanied by vascular deposits of β-amyloid peptide in 7. Compared to the 178 patients without TLM, the patients with TLM were more likely to be male (p = 0.04), and less likely to have a transient ischemic attack (p = 0.023), bilateral cerebral infarcts (p = 0.018), or vasculitic lesions on angiography (p = 0.045). They were more likely to have seizures (p = 0.022), gadolinium-enhanced lesions (p = 0.007), and amyloid angiopathy (p = 0.046). All 13 patients responded to therapy and 8/13 (61.5%) had a Rankin disability score of 0 at last visit. Overall, high disability scores (Rankin scores 4–6) at last follow-up were associated with increasing age (odds ratio, OR, 1.49) and cerebral infarction (OR, 3.47), but were less likely in patients with gadolinium-enhanced lesions (OR, 0.36) and amyloid angiopathy (OR, 0.21).

Conclusion

In PCNSV a TLM at presentation represents a definable subgroup of patients with a favourable treatment response.

https://ift.tt/2OSzQ4v

Discoid lupus erythematosus: Reflectance confocal microscopy features correlate with horizontal histopathological sections

Skin Research and Technology, EarlyView.

https://ift.tt/2OSNG7e

Dynamic thermal imaging on actinic keratosis patients: A preliminary study

Skin Research and Technology, EarlyView.

https://ift.tt/2O82cTn

Minimal erythema dose, minimal persistent pigment dose which model for whitening products evaluation is better?

Skin Research and Technology, EarlyView.

https://ift.tt/2ONqXZX

Ultrasound‐guided fine‐needle aspiration biopsy in skin lesions

Skin Research and Technology, EarlyView.

https://ift.tt/2O8rd0y

Age‐related changes in lip morphological and physiological characteristics in Korean women

Skin Research and Technology, EarlyView.

https://ift.tt/2OM99hO

Methotrexate and melanoma‐specific mortality

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2Sj5V3G

First psychodermatology clinic in a Portuguese department of Dermatology

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2z6CrNM

Inherited epidermolysis bullosa: description of clinical and subclinical morphological features with optical coherence tomography

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2ShjbWo

Increased tumour cell PD‐L1‐expression, macrophage and dendritic cell infiltration characterise the tumour microenvironment of ulcerated primary melanomas

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2z1ZE3r

JAK1/3‐inhibition preserves epidermal morphology in full thickness 3D skin models of atopic dermatitis and psoriasis

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2Si5ab5

Validation of “ItchApp©” in Poland and in the USA Multicenter validation study of an electronical Diary for the Assessment of pruritus

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2z2Jy9Q

Post‐orf epidermolysis bullosa acquisita

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2Shjb8Q

Associations between whole tumor histogram analysis parameters derived from ADC maps and expression of EGFR, VEGF, Hif 1-alpha Her-2 and Histone 3 in uterine cervical cancer

Publication date: Available online 25 October 2018

Source: Magnetic Resonance Imaging

Author(s): Hans-Jonas Meyer, Peter Gundermann, Anne Kathrin Höhn, Gordian Hamerla, Alexey Surov

Abstract

Objective

Diffusion weighted imaging (DWI) can be quantified by apparent diffusion coefficient (ADC) and can predict tissue microstructure. The aim of the present study was to analyze possible associations between ADC histogram based parameters with different histopathological parameters in cervical squamous cell carcinoma.

Materials and methods

18 female patients (age range 32–79 years) with squamous cell cervical carcinoma were retrospectively enrolled. In all cases, pelvic MRI was performed with a DWI (b-values 0 and 1000 s/mm²). Histogram analysis was performed as a whole lesion measurement. Histopathological parameters included expression of EGFR, VEGF, Hif1-alpha, Her2 and Histone 3. Spearman's correlation coefficient was used to analyze associations between investigated parameters.

Results

Analyze of the investigated ADC histogram parameters showed a good interreader variability, ranging from 0.705 for entropy to 0.959 for ADCmedian. EGFR expression correlated statistically significant with several histogram parameters. The highest correlation was observed for p75 (p = −0.562, P = 0.015). There were several correlations with histone 3, the highest with p25 (p = −0.610, P = 0.007). None of the ADC related parameters correlated statistically significant with expression of VEGF, Hif1-alpha and Her2.

Conclusion

Histogram analysis showed a good interreader agreement. ADC histogram parameters might be able to reflect expression of EGFR and histone 3 in cervical squamous cell carcinomas, but not expression of VEGF, Hif1-alpha and Her2.

https://ift.tt/2ArAEo6

Aggressive-Appearing Intratracheal Mass in an Older Woman

A woman in her early 70s presents with biphasic stridor and a report of dyspnea on mild exertion. Noncontrast computed tomography of the chest shows a lesion protruding into the right side of the tracheal region that appears to be contiguous with the right lobe of the thyroid gland. Examination of a biopsy specimen shows medullary thyroid cancer. What is your diagnosis?

https://ift.tt/2PlrG3Z

Reduction of Opiates for Ambulatory Surgery

According to the US Department of Health and Human Services, 116 people die every day in this country from an opioid-related overdose. That statistic represents more than 42 000 people a year, more than the annual number of deaths due to automobile crashes or homicides. In 2014, 47 055 drug overdose deaths occurred in the United States, and 60.9% of those involved an opioid. The following year, this number grew to 53 000 deaths and the percentage involving at least 1 opioid drug increased to 63.1%. In 1999, only 180 morphine milligram equivalents (MME) per capita were sold in the United States. In 2015, 640 MMEs per capita were sold, representing a 3.6-times increase.

https://ift.tt/2JfRoS9

Opioid Prescribing Practice and Needs in Thyroid and Parathyroid Surgery

This cohort study assesses the opioid prescribing practices and opioid needs for patients undergoing thyroid and parathyroid surgery.

https://ift.tt/2PlrFNt

Characterizing the Normative Voice Tremor Frequency in Essential Vocal Tremor

This cross-sectional observational study characterizes the normative voice tremor frequency in patients with essential vocal tremor.

https://ift.tt/2JfRmK1

The Use of Osteopathic Medical Manipulation to Decrease the Incidence and Severity of Post-Operative Sore Throat

Conditions: Pharyngitis; Dysphonia
Interventions: Procedure: Osteopathic Manipulation Treatment; Procedure: Sham
Sponsor: Brooke Army Medical Center
Recruiting

https://ift.tt/2OP7SH2

Early Support in Primary Care for People Starting Treatment for Cancer

Conditions: Cancer of Pancreas; Cancer of Stomach; Cancer of Esophagus
Intervention: Other: Anticipatory care planning letter
Sponsors: NHS Lothian; NHS Fife
Recruiting

https://ift.tt/2RkJQ3x

Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy

Conditions: HRAS Gene Mutation; HNSCC
Interventions: Drug: Tipifarnib; Device: HRAS Detection Assay
Sponsor: Kura Oncology, Inc.
Not yet recruiting

https://ift.tt/2OONIgl

Enteral Omega 3 During Radiotherapy to Improve the Quality of Life and Functionality of Head and Neck Cancer Patients

Conditions: Head and Neck Squamous Cell Carcinoma; Quality of Life; Radiotherapy; Complications
Interventions: Dietary Supplement: Omega 3 Group; Dietary Supplement: Placebo or Control Group
Sponsor: Coordinación de Investigación en Salud, Mexico
Recruiting

https://ift.tt/2R9GP5G

Nal-iri/lv5-fu Versus Paclitaxel as Second Line Therapy in Patients With Metastatic Oesophageal Squamous Cell Carcinoma

Condition: Squamous Cell Carcinoma
Interventions: Drug: Onivyde; Drug: Paclitaxel
Sponsors: Federation Francophone de Cancerologie Digestive; Shire
Not yet recruiting

https://ift.tt/2OO0cEF

Robot-assisted Approach to Cervical Cancer

Condition: Cervical Cancer
Interventions: Procedure: Abdominal radical hysterectomy; Procedure: Robot-assisted radical hysterectomy; Diagnostic Test: Sentinel lymph node biopsy
Sponsor: Karolinska Institutet
Not yet recruiting

https://ift.tt/2RgxvgB

Acute Radiation Oral Mucositis in Nasopharyngeal Carcinoma(NPC) Patients Treated With Combined Radio-Chemotherapy

Condition: Nasopharyngeal Carcinoma
Interventions: Drug: Recombinant Human Interleukin-11; Drug: Saline
Sponsor: Zhejiang Cancer Hospital
Recruiting

https://ift.tt/2OMlBye

The Use of Osteopathic Medical Manipulation to Decrease the Incidence and Severity of Post-Operative Sore Throat

Conditions: Pharyngitis; Dysphonia
Interventions: Procedure: Osteopathic Manipulation Treatment; Procedure: Sham
Sponsor: Brooke Army Medical Center
Recruiting

https://ift.tt/2OP7SH2

Early Support in Primary Care for People Starting Treatment for Cancer

Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy

Conditions: HRAS Gene Mutation; HNSCC
Interventions: Drug: Tipifarnib; Device: HRAS Detection Assay
Sponsor: Kura Oncology, Inc.
Not yet recruiting

https://ift.tt/2OONIgl

Enteral Omega 3 During Radiotherapy to Improve the Quality of Life and Functionality of Head and Neck Cancer Patients

Nal-iri/lv5-fu Versus Paclitaxel as Second Line Therapy in Patients With Metastatic Oesophageal Squamous Cell Carcinoma

Robot-assisted Approach to Cervical Cancer

Acute Radiation Oral Mucositis in Nasopharyngeal Carcinoma(NPC) Patients Treated With Combined Radio-Chemotherapy

Condition: Nasopharyngeal Carcinoma
Interventions: Drug: Recombinant Human Interleukin-11; Drug: Saline
Sponsor: Zhejiang Cancer Hospital
Recruiting

https://ift.tt/2OMlBye

Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma

Abstract

Background

Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4⁺, CD8⁺ and/or CD103⁺ TIL status in patients with advanced LSCC.

Methods

Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4⁺, CD8⁺, and CD103⁺ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4⁺, CD8⁺, and CD103⁺ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC.

Results

High tumor CD103⁺ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8⁺ or CD4⁺ TIL content. On multivariate analysis, an "immune-rich" phenotype, in which tumors were enriched for both CD103⁺ and CD4⁺ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC.

Conclusions

An immune profile driven by CD103⁺ TIL content, alone and in combination with CD4⁺ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.

https://ift.tt/2O6kkN6

Non-cystic Sclerosing Polycystic Adenosis: Diagnosis of a Hitherto Undescribed Pattern

Abstract

A case of sclerosing polycystic adenosis without cysts is described. The lesion occurred as a painless slow growing superficial right parotid lump in a 47 years old woman. The tumor measured 14 × 10 mm and displayed extreme well circumscription, sclerotic stroma with scattered hyaline nodules, sprinkling of mononuclear inflammatory cells and islands of mature fat. The epithelial component was predominantly composed of tubules lined by low columnar to cuboidal epithelium with bland nuclear features. Only focal incomplete acinar differentiation with few cells containing small eosinophilic granules was present. The stroma contained a significant fibromyxoid component with increased cellularity. There was no recurrence on follow-up at 14 months.

https://ift.tt/2O3sExn

Combined Growth Factor and Gene Therapy: An Approach for Hair Cell Regeneration and Hearing Recovery

Introduction: Fibroblast growth factor, nerve growth factor neurotrophins, and insulin-like growth factor 1 are considered 3 families of growth factors that can be involved in the process of otic neurogenesis. In this respect, otic neurons can also be connected with mechanoreceptors in the ear, the hair cells (HCs), as well as the central nervous system. As a growth factor is combined with gene transfer technology, it can be used for hair cell regeneration. Gene therapy can be similarly employed to introduce genes into a system in order to induce the expression of genes for therapeutic agents, to replace defective genes, or to re-program supporting or surrounding cells to acquire the phenotype of lost or damaged cells in order to repair or regenerate the damaged tissue. Objective: The purpose of this review article was to investigate the epigenetic and growth factors involved in the differentiation pathway of embryonic stem cells (ESCs) into HCs and auditory neurons (ANs). Methods: To this end, the databases of Directory of Open Access Journals, Google Scholar, PubMed (NLM), LISTA (EBSCO), as well as Web of Science were searched. Results: Given the results available in the related literature, the differentiation efficacy of ESCs toward the ANs and the HCs, the important role of growth factors, and 3 different strategies of application of miRNA, epigenetic regulation, and preparation of three-dimensional (3D) environments were suggested to be taken into consideration in order to improve these studies in the future. Furthermore, the role of epigenetic mechanisms and miRNA in this differentiation process became quite obvious; hence, the utilization of such procedures in the near future would be significant. Conclusion: Combining several techniques with a synergic effect (such as growth factor gene therapy and 3D environments) seemed to lead to obtaining the best results as a therapeutic strategy.
ORL

https://ift.tt/2CEUwpi

Association of Multiple Sclerosis with Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies

Abstract

Background

Previous studies have reported the occurrence of psoriasis together with multiple sclerosis (MS). Although similar predisposing genes and pathomechanisms have been hypothesized, the relationship between the two remains obscure.

Objective

The aim of this systematic review and meta-analysis was to investigate the association between psoriasis and MS.

Methods

We searched MEDLINE, Embase, and CENTRAL in July 2018 for case–control, cross-sectional, or cohort studies that examined either the odds or risk of psoriasis in subjects with multiple sclerosis. The risk of bias of included studies was assessed using the Newcastle–Ottawa Scale. A random-effects model meta-analysis was used to calculate the odds ratio (OR) for case–control/cross-sectional studies and hazard ratio (HR) for cohort studies.

Results

We included 10 publications that reported a total of 11 studies (5 case–control, 4 cross-sectional and 2 cohort studies). The case–control and cross-sectional studies included 18,456 MS patients and 870,149 controls, while the two cohort studies involved 25,187 MS patients and 227,225 controls in total. Three studies were rated with a high risk of bias in comparability, non-response rate, and selection of controls. MS was associated with increased odds (OR 1.29; 95% confidence interval [CI] 1.14–1.45) and risk for psoriasis (HR 1.92; 95% CI 1.32–2.80).

Conclusion

Patients with MS display both increased prevalence and incidence of psoriasis.

https://ift.tt/2PReGAh

Cutaneous Adverse Effects of Diabetes Mellitus Medications and Medical Devices: A Review

Abstract

Diabetes mellitus is one of the most prevalent chronic diseases in the USA. If uncontrolled, diabetes can lead to devastating complications. Diabetes medications and medical devices largely contribute to the significant financial expense that the disease inflicts on affected individuals and society. Alongside significant economic burden, there are numerous cutaneous adverse effects associated with diabetes medications and medical devices. Despite the large and increasing number of individuals living with diabetes and the wide use of the related medications and medical devices, there is limited literature that comprehensively documents their cutaneous adverse effects. These cutaneous adverse effects are significant as they can worsen glycemic control, increase disease distress, and may increase risk of associated complications. Thus, it is important that providers can recognize these cutaneous adverse effects, identify the culprit agents, and can properly manage them. In this article, we provide a critical review of the cutaneous adverse effects of medications and devices used in the management of diabetes and provide insight into risk factors and prevention and an overview of therapeutic management. An emphasis is placed on clinical recognition and treatment for use of the medical providers who, regardless of practice setting, will treat patients with diabetes.

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Vocal Cord Palsy as a Complication of Epidural Anaesthesia

Cranial nerve palsy is a rare but recognised complication of epidural anaesthesia, most commonly presenting as diplopia secondary to abducens nerve palsy. While upper cranial nerve palsies have been documented on numerous occasions, lower cranial nerve palsies, including recurrent laryngeal nerve palsy, are exceedingly rare. This case describes a 37-year-old female who, following epidural anaesthesia for spontaneous vaginal delivery of her first child, presented with dysphonia. Flexible laryngoscopy confirmed a left vocal cord palsy, and computed tomography ruled out any mass lesions along the course of the recurrent laryngeal nerve. Here, we discuss a case of vocal cord palsy secondary to epidural anaesthesia, an extremely rare complication. We also discuss the proposed etiology, treatment, and outcomes in patients with this condition. Cranial nerve palsy should be an important differential in patients presenting with dysphonia following spinal or epidural anaesthesia.

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Non-cystic Sclerosing Polycystic Adenosis: Diagnosis of a Hitherto Undescribed Pattern

Abstract

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Ungewöhnlicher Tumor der Schädelbasis mit Ausdehnung in die Halsweichteile

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A Young Male with Parafibromin-Deficient Parathyroid Carcinoma Due to a Rare Germline HRPT2/CDC73 Mutation

Abstract

Hyperparathyroidism, commonly observed in asymptomatic middle-aged women, with mild hypercalcemia, is usually caused by a benign adenoma. Some cases present with more severe manifestation and greater hypercalcemia. Within this spectrum, several familial/genetic associations have been discovered. While the majority are caused by benign disease, adenomas, or hyperplasia, a small proportion (< 1%) are associated with malignant tumors and present with more severe symptoms. Although usually sporadic, recent reports document various gene mutations that strongly predispose to the development of parathyroid carcinoma. An increasing number of cases of hyperparathyroidism, benign or malignant, require and benefit from genetic analysis. We describe a 25-year-old male with hyperparathyroidism presenting with a pathological fracture, brown tumors, hypercalcemia, and markedly elevated parathyroid hormone levels. There was no family history of hyperparathyroidism or jaw tumors. Surgical removal revealed a single large tumor confirmed to be malignant. Immunohistochemical analysis revealed the absence of parafibromin and decreased APC (adenomatosis polyposis coli) expression. Genetic analysis revealed a rare germline nonsense mutation (R76X) in the parafibromin gene, HRPT2/CDC73. Parathyroid carcinoma should be suspected as a cause of hyperparathyroidism when clinical manifestations are severe, particularly in young individuals, < 59 years. Immunohistochemistry may lead to suspicion for a germline mutation as a significant contributor despite absence of a family history. The discovery of a germline mutation in parathyroid carcinoma alters the clinical management of the index case and that of family members. Long-term follow-up studies of such patients are necessary to develop evidence-based clinical guidelines.

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Non-cystic Sclerosing Polycystic Adenosis: Diagnosis of a Hitherto Undescribed Pattern

Abstract

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Individualized treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels

Publication date: Available online 24 October 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Congxiang Shen, Fang Chen, Huigang Wang, Xinyu Zhang, Guanxue Li, Zhong Wen

Abstract

Introduction

The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity.

Objective

To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies.

Methods

A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors.

Results

Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05).

Conclusion

Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

Resumo

Introdução

A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas.

Objetivo

Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica, e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos.

Método

Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1.

Resultados

As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05).

Conclusão

A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.

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Regulatory T cell therapy for autoimmune and autoinflammatory diseases: the next frontier

Publication date: Available online 25 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Jonathan H. Esensten, Yannick D. Muller, Jeffrey A. Bluestone, Qizhi Tang

Unstructured abstract

FOXP3-expressing regulatory T cells (Tregs) are essential for self-tolerance with an emerging role in tissue repair and regeneration. Their ability to traffic to tissue and perform complex therapeutic tasks in response to the tissue microenvironment make them an attractive candidate for drug development. Early experiences of Treg cell therapy in graft-versus-host disease, type 1 diabetes, and organ transplant have shown that it is feasible, safe, and potentially efficacious in some settings. Many ongoing trials in a wide variety of diseases will further enhance our knowledge about the optimal approaches for Treg manufacturing and dosing. We review the current preclinical rationale supporting Treg therapy in a variety of disease settings ranging from tissue transplantation, autoimmune diseases, and non-immune-mediated inflammatory settings. We point out challenges in development of Treg cell therapy and speculate how synthetic biology may be used to enhance the feasibility and efficacy of Treg therapy for autoimmune and autoinflammatory diseases.

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Analysis of eosinophilic esophagitis in children with repaired congenital esophageal atresia

Publication date: Available online 24 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Usha Krishnan, Chan Lijuan, Gifford J. Andrew, Marc E. Rothenberg, Ting Wen

Background

A high prevalence of eosinophilic esophagitis (EoE) has been preliminarily reported in patients after repair of esophageal atresia (EA), but the basis of this association is unknown.

Objectives

We aimed to (1) characterize the EoE transcriptome in patients with EA, (2) compare the EoE transcriptome in patients with EoE and EA with that in patients with EoE alone, and (3) identify transcripts that could predispose patients with EA to EoE.

Methods

This single-center, population-based, retrospective study identified 4 EoE study cohorts: healthy control subjects, patients with EA and EoE (EA+EoE+), patients with EA without EoE (EA+EoE−), and patients with EoE without EA (EA−EoE+). Molecular signatures were assessed by using the EoE diagnostic panel, a 94-gene expression quantitative PCR array.

Results

In a cohort of 110 pediatric patients with surgically repaired EA, 20 (18%) patients were given a diagnosis of EoE, representing a 364-fold enrichment of EoE in patients with EA compared with the general pediatric population. EoE diagnostic panel analyses revealed a major overlap between the EA+EoE+ and EA−EoE+ cohorts. A proportion (approximately 25%) of EoE signature genes were dysregulated in patients with EA+EoE− compared with healthy control subjects, including those involved in epithelial barrier function and type 2–associated inflammatory responses. Patients with EA+EoE+ exhibit a more severe EoE clinical phenotype than those with EA−EoE+ in terms of dysphagia and dilation need.

Conclusions

Patients with EA have increased risk of EoE. Patients with EoE with EA have a similar molecular profile compared with that of patients with EoE without EA. Dysregulated baseline epithelial barrier and type 2–associated genes in EA monomorbidity might explain the higher EoE prevalence in patients with EA.

Graphical abstract

Graphical abstract for this article

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Integrative approach identifies corticosteroid response variant in diverse populations with asthma

Publication date: Available online 24 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Albert M. Levin, Hongsheng Gui, Natalia Hernandez-Pacheco, Mao Yang, Shujie Xiao, James J. Yang, Samantha Hochstadt, Andrea J. Barczak, Walter L. Eckalbar, Dean Rynkowski, Lesly-Anne Samedy, Pui-Yan Kwok, Maria Pino-Yanes, David J. Erle, David E. Lanfear, Esteban G. Burchard, L. Keoki Williams

Abstract

Background

Although inhaled corticosteroid (ICS) medication is considered the cornerstone treatment for patients with persistent asthma, few ICS pharmacogenomic studies have involved non-white populations.

Objective

To identify genetic predictors of ICS response in multiple population groups with asthma.

Methods

The discovery group comprised African American participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) who underwent 6 weeks of monitored ICS therapy (n=244). A genome-wide scan was performed to identify single nucleotide polymorphism (SNP) variants jointly associated (i.e., the combined effect of the SNP and SNP x ICS treatment interaction) with changes in asthma control. Top associations were validated by assessing the joint association with asthma exacerbations in three additional groups – African Americans (n=803 and n=563) and Latinos (n=1,461). RNA-seq data from 408 asthma cases and 405 controls were used to examine whether genotype was associated with gene expression.

Results

One variant, rs3827907, was significantly associated with ICS-mediated changes in asthma control in the discovery set (P=7.79x10^-8) and was jointly associated with asthma exacerbations in three validation cohorts (P=0.023, P=0.029, and P=0.041). RNA-seq analysis found the rs3827907 C-allele to be associated with lower RNASE2 expression (P=6.10x10-4). RNASE2 encodes eosinophil-derived neurotoxin (EDN), and the rs3827907 C-allele appeared to particularly influence ICS treatment response in the presence of eosinophilic inflammation (i.e., high pre-treatment EDN levels or blood eosinophil counts).

Conclusion

We identified a variant, rs3827907, which appears to influence response to ICS treatment in multiple population groups, and likely mediates its effect through eosinophils.

Clinical Implications

African Americans and Latinos are disproportionately affected by asthma and its complications. Here we identify a pharmacogenomic variant that may assist in identifying individuals from these groups who will respond to ICS treatment.

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“Evaluating primary endpoints in peanut immunotherapy clinical trials”

Publication date: Available online 24 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Pablo Rodríguez del Río, Carmelo Escudero, Silvia Sánchez-García, María Dolores Ibáñez, Brian P. Vickery

Abstract

Food immunotherapy has been the focus of several allergy research initiatives over the last decade. Though many questions remain unanswered, the evidence suggests that this treatment may be available in the near future outside clinical trials. Additionally, pharmaceutical companies, in light of promising early stage results, have shown interest in developing commercially available products, thus increasing the likelihood that new immunotherapy treatments will be introduced, especially for peanut allergy.

Given this optimistic scenario, and given the prospect of rigorously developed products for peanut allergy treatment, each allergist will need to understand the specificities of these treatments and their expected efficacy and adverse event profiles. It is thus imperative that allergists understand the differences in efficacy between the different management options as well as how the endpoints are measured in the relevant literature. However, given the significant heterogeneity detected among food immunotherapy trials, this task may not be as straightforward as desired.

This article aims to dissect how primary efficacy endpoints are defined and assessed in order to facilitate understanding of the design of these trials and the potential impact that this variation may have on the reported outcomes.

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The different roles of 5-HT1A/2A receptors in fluoxetine ameliorated pigmentation of C57BL/6 mouse skin in response to stress

Publication date: Available online 25 October 2018

Source: Journal of Dermatological Science

Author(s): Liangliang Zhou, Minxuan Cai, Yingying Ren, Huali Wu, Meng Liu, Haijuan Chen, Jing Shang

Abstract

Background

5-HT1 A receptor was participated in fluoxetine induced melanogenesis in melanocytes and in normal C57BL/6 mice, but we know little about whether other 5-HT receptors are involved in regulation of fluoxetine promotes pigmentation.

Objective

To investigate the role of 5-HT receptors in regulation of fluoxetine ameliorates chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) induce hypopigmentation in C57BL/6 mice.

Methods

CUMS and CRS were used to induce depigmentation in mice and evaluate the effect of fluoxetine. Western blot, immunohistochemistry and Q-PCR assay were used to determine the levels of protein and mRNA. Masson Fontana staining was used for melanin staining and FITC-Phalloidin staining was used to detect the expression of F-actin. Zebrafish and B16F10 cells were used for the mechanism research.

Results

Fluoxetine (2.6 mg/kg, ig) ameliorated hypopigmentation induced by CUMS and CRS in mice, significantly increased the mRNA and protein levels of 5-HT1 A and 5-HT2 A receptors in mice and B16F10 cells. The effect of fluoxetine on melanogenesis in B16F10 cells and zebrafish were inhibited by WAY100635 (a selective 5-HT1 A receptor antagonist) and ketanserin (a 5-HT2 A receptor antagonist), respectively. Activation of p38 MAPK signaling pathways was contributed to fluoxetine induced melanogenesis and inhibited by WAY100635, but not ketanserin. However, ketanserin selectively weakened the action of fluoxetine promoted migration and up-regulated Rab27a protein expression in B16F10 cells.

Conclusions

5-HT1 A and 2 A receptors contribute to melanogenesis and migration property of fluoxetine. The newly revealed mechanism indicates that fluoxetine and its analogues may be a potential drug for treatment of depigmentation disorders.

Graphical Abstract

Graphical abstract for this article

Stress, specifically chronic unpredictable stress and chronic restrained stress, induce depigmentation in C57BL/6 mice. Fluoxetine promoted melanin production and the migration of melanocytes via 5-HT1 A receptor and 5-HT2 A receptor, respectively.

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Sialorrhea & aspiration control - A minimally invasive strategy uncomplicated by anticholinergic drug tolerance or tachyphylaxis

Publication date: Available online 24 October 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Joseph E. Dohar

Abstract

Objective

Sialorrhea complicated by aspiration is a primary source of morbidity and mortality in neurologically impaired children. Anticholinergics are an effective treatment option, but have traditionally been considered only adjuncts due to tachyphylaxis and drug tolerance. Similarly, Botox-A® salivary gland injections are also considered adjunctive due to the need to repeat treatment every 3 months. This retrospective case series assessed these two adjunctive strategies used in combination as definitive minimally invasive primary treatment.

Methods

112 subjects diagnosed with sialorrhea and treated at Children's Hospital of Pittsburgh of UPMC between 2004 and 2011 were identified. Charts were carefully reviewed for pertinent information regarding the treatment of their sialorrhea and related outcomes.

Results

Over half of the subject undergoing BTX-A injections were able to reduce their dosage of anticholinergics after receiving injection (58%, n=28 for glycopyrrolate users and 61%, n=20 for scopolamine users). Subjects experienced a significant reduction in days spent in the hospital in the year following Botox-A® injection (P-Value = 0.03), and the number of pneumonia episodes in the year following injection (P-Value = 0.04).

Conclusion

Patients treated effectively with both BTX-A injections into their salivary glands and anticholinergics neither developed neither tachyphylaxis nor drug tolerance with up to 9.6 years of continuous treatment. During the year following combined therapy, patients' average length hospital stay was reduced by a full week and the number of pneumonia episodes was statistically decreased. The failure rate of combined therapy was below that reported for any other intervention or combination of interventions in the literature. Finally, patients did not require BTX-A re-injection at the reported frequency. We hypothesize that anticholinergic medications competitively block acetylcholine attachment to post-synaptic receptors while BTX-A inhibits acetylcholine release at the pre-synaptic terminal, tachyphylaxis/drug tolerance mechanisms resulting in up-regulation of post-synaptic receptors are disrupted. Although salivary production may increase in the year following BTX-A injection, there is enough remaining activity at a molecular level to inhibit release of acetylcholine allowing salvage with anticholinergic medications at tolerable dosages.

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Kurdish Speech Test: A Validation Study for Children Aged 3-5 Years

Publication date: Available online 24 October 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Shahla Fatemi Syadar, Talieh Zarifian, Yahya Modarresi, Muhamad Sediq Zahedi, Mona Ebrahimipour, Akbar Biglarian

Abstract

Objectives

Speech disorder in children is the most common disorder reported by speech and language pathologists in all languages and its evaluation and diagnosis requires valid and reliable tools. This study aimed to develop a Kurdish Speech Test for children aged 3-5 years and to determine its psychometric properties.

Methods

The validation included 120 monolingual Kurdish-speaking children aged 3-5 years in the city of Bukan, Iran. Content validity was determined according to expert opinions of Kurdish speech and language pathologists and linguists. Test-retest (one-week interval) and scoring-rescoring by two independent examiners were conducted to determine intra- and inter-rater reliability. The tests ability to discriminate between four age groups (36-60 months) was investigated for construct validity. Differences related to gender were assessed.

Results

Intra- and inter-rater reliability showed no significant difference between the first and second week of administration (p<0.001) and scoring-rescoring by two independent raters confirmed the reliability of the Kurdish Speech Test (P<0.001). Discriminating properties, reflecting construct validity showed higher scores with increasing age. No gender differences were found.

Conclusion

The Kurdish Speech Test is a reliable and valid instrument for evaluation of articulation in three-to-five-year-old children. Results suggest that the test is appropriate for clinical assessment of children with speech sound disorders.

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Why some surgeons no longer systematically operate cases of papillary thyroid carcinoma

Publication date: Available online 25 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): F. Rubin, A. Ait-Boudaoud, Q. Lisan

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Transoral robotic surgery of the tongue base for obstructive sleep apnea: Preliminary results

Publication date: Available online 24 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): G. de Bonnecaze, B. Vairel, A. Dupret-Bories, E. Serrano, S. Vergez

Abstract

Introduction

Obstructive sleep apnea syndrome (OSAS) is a major public health issue. Robotic tongue-base reduction surgery is being developed, but needs assessment. The present study reports clinical and polygraphic results at 6 months' follow-up.

Method

Single-center prospective study of 8 patients undergoing transoral robotic surgery (TORS) for severe OSAS.

Results

Mean age was 47 years. M/F sex ratio was 5:3. Initial body-mass index ranged from 18 to 35 kg/m². Mean Epworth score was 12. Mean preoperative apnea-hypopnea index (AHI) was 47 (range, 36–60). At 6 months, only 1 patient did not meet usual success criteria (AHI < 20 with > 50% decrease); 2 patients had residual AHI between 10 and 20; the other 5 had non-significant event rates.

Conclusion

TORS tongue-base reduction showed promising results, which need confirmation on long-term multicenter studies.

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Conflict of interest and citation impact among dermatology guideline authors

Publication date: Available online 24 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Kamber Loren Hart, Roy Howard Perlis, Clifford Scott Perlis

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Effect of Post-Injection Facial Exercise on Time of Onset of Botulinum Toxin for Glabella and Forehead Wrinkles: A Randomized Controlled, Crossover Clinical Trial

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Iris Morphological Features in Patients with 360° Angle-Closure Neovascular Glaucoma: An Anterior Segment Optical Coherence Tomography Study

Purpose: To investigate iris morphological features in 360° angle-closure neovascular glaucoma (NVG) by swept-source anterior segment optical coherence tomography (ASOCT). Patients and Methods: In this retrospective, clinic-based, comparative study, 14 patients with 360° angle-closure NVG and 14 healthy age-matched control subjects were enrolled. All patients enrolled had no prior glaucoma surgery but underwent cataract surgery with intraocular lens implantation. Horizontal scanning images of swept-source ASOCT were analyzed using software calipers in temporal and nasal angle areas. The iris thickness at 1 and 2 mm from the pupil edge, iris length, trabecular meshwork length, peripheral anterior synechia (PAS) length, PAS height ratio (PAS length/trabecular meshwork length), and pupil diameter were measured. Results: Between the groups, there were no statistically significant differences in iris length, trabecular meshwork length, and pupil diameter (p #x3e; 0.05). However, the iris thickness was significantly reduced in the NVG group compared with the control group in the temporal and nasal areas (0.306 vs. 0.563 mm/0.326 vs. 0.645 mm at 1 mm, 0.278 vs. 0.523 mm/0.282 vs. 0.546 mm at 2 mm, respectively) (mean, all p #x3c; 0.001). In the NVG group, PAS height ratios were 1.55 ± 0.45 (mean ± standard deviation) (range, 0.58–2.30) and 1.55 ± 0.78 (range, 0.68–3.68) at the temporal and nasal angles, respectively. Conclusions: In patients with 360° angle-closure NVG, the iris thickness decreased to about 50% of that in healthy subjects, and the PAS length exceeded the trabecular meshwork length by about 1.5 times.
Case Rep Ophthalmol 2018;9:449–456

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Hypogammaglobulinemia with decreased class-switched B-cells and dysregulated T-follicular-helper cells in IPEX syndrome

Publication date: Available online 24 October 2018

Source: Clinical Immunology

Author(s): Oded Shamriz, Kiran Patel, Rebecca A. Marsh, Jacob Bleesing, Avni Y. Joshi, Laura Lucas, Chengyu Prince, Bojana B. Pencheva, Lisa Kobrynski, Shanmuganathan Chandrakasan

Abstract

Early onset multisystem autoimmunity is commonly the defining feature of IPEX. Recurrent sinopulmonary infections and CVID-like phenotype were not previously recognized as a presentation in IPEX. Herein, we describe three extended family members with IPEX. In addition to autoimmunity, all three had a CVID-like presentation consisting of recurrent sinopulmonary infections, hypogammaglobulinemia and B-cell class switching defect. In vitro studies have shown that the B cell class switching defect is not B cell intrinsic. Additionally, a marked increase in circulating T follicular helper (cTFH) cells with high IFN-γ and IL-17 secretion on stimulation was noted in our patients. The dysregulated cTFH cells could contribute to a decreased B cell class switching. However, the exact mechanism of how expanded and dysregulated cTFH lead to B cell class switching defect and hypogammaglobulinemia in our patients is not clear. Our study could extend the clinical spectrum of IPEX to include a CVID-like presentation.

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Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Πέμπτη 25 Οκτωβρίου 2018

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