Tracking small sensory nerve action potentials in human axonal excitability studies

Publication date: Available online 11 February 2018
Source:Journal of Neuroscience Methods
Author(s): James Howells, Hugh Bostock, Susanna B. Park, Matthew C. Kiernan, David Burke
BackgroundExcitability studies on normal and diseased human axons in vivo have been greatly enhanced by fast non-invasive threshold-tracking techniques, using surface stimulation and recording. Although sensory axons are often more affected in disease, most studies to date have focussed on motor axons, because of technical difficulties in resolving pathologically small nerve volleys in the presence of noise and stimulus artefact.New MethodsThis paper describes techniques for tracking low-amplitude compound action potentials, using a battery-powered, isolated preamplifier of simple construction with high common mode rejection (>125 dB [balanced inputs]) and low noise (<0.4 μV referred to inputs [shorted]).ResultsWe demonstrate the preamplifier's capability by tracking targets as small as 2 μV for a full range of excitability measurements without the usual distortion due to residual stimulus artefact and without the need for clamping, additional filtering or ensemble averaging.Comparison with existing methodsIn practice, threshold-tracking studies have been unable to study sensory axons when the maximal compound sensory action potential was less than about 15 μV. The techniques and amplifier in the present study allow measurements to be made from nerve with maximal responses less than half that size, and we present three recordings in patients with pathologically small nerve action potentials ≤7 μV.ConclusionsBased on measurements of stimulus artefact distortion, noise and the performance in experiments, we conclude that the techniques described here will facilitate the study of diseased axons for which the sensory potentials have high thresholds and may be only a few microvolts in amplitude.



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Phacomatosis pigmentokeratotica: a case of HRAS mosaicism causing rhabdomyosarcoma

Abstract

A 17-year-old male presented with a large sebaceous naevus (SN) comprising part of his left face and scalp and a speckled lentiginous naevus (SLN) on his right trunk, hip, neck and scalp with a checkerboard pattern. His right oral hemimucosa showed extensive papillomatous lesions which were contiguous to the upper lip SN lesions. As for extracutaneous manifestations he suffered from cardiac, musculoskeletal and ocular alterations. On the other hand, he developed two primary rhabdomyosarcomas. DNA samples of the SN, SLN, the oral papillomatous hyperplasia and both rhabdomyosarcomas were analyzed by Sanger sequencing. A HRAS c.37G>C mutation was detected in all of them. Skin and blood DNA resulted wild type. PPK is characterized by the association of a sebaceous naevus with a papular naevus spilus and extracutaneous manifestations. Until not long ago, the etiopathogenetical hypothesis of didymosis was accepted. However, in 2013 Groesser et al. proved the existence of an activating HRAS mutation as the cause of this syndrome. A higher incidence of cancer has been observed in germline RASophaties. Furthermore, up to 30% of human cancers show dysregulation of the Ras-Raf-MEK-ERK pathways. In our patient, a HRAS mosaic mutation explains not only the cutaneous but also the extracutaneous manifestations. To our knowledge this is the first described case of PPK in which the existence of a HRAS mosaic mutation is the confirmed cause of rhabdomyosarcoma. Besides the HRAS 37G>C mutation has never been related to any type of rhabdomyosarcoma. Mosaicisms could be underdiagnosed causes of childhood tumours. As dermatologists we stand on a privileged position for the detection of these alterations.

This article is protected by copyright. All rights reserved.

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Phacomatosis pigmentokeratotica: a case of HRAS mosaicism causing rhabdomyosarcoma

Abstract

A 17-year-old male presented with a large sebaceous naevus (SN) comprising part of his left face and scalp and a speckled lentiginous naevus (SLN) on his right trunk, hip, neck and scalp with a checkerboard pattern. His right oral hemimucosa showed extensive papillomatous lesions which were contiguous to the upper lip SN lesions. As for extracutaneous manifestations he suffered from cardiac, musculoskeletal and ocular alterations. On the other hand, he developed two primary rhabdomyosarcomas. DNA samples of the SN, SLN, the oral papillomatous hyperplasia and both rhabdomyosarcomas were analyzed by Sanger sequencing. A HRAS c.37G>C mutation was detected in all of them. Skin and blood DNA resulted wild type. PPK is characterized by the association of a sebaceous naevus with a papular naevus spilus and extracutaneous manifestations. Until not long ago, the etiopathogenetical hypothesis of didymosis was accepted. However, in 2013 Groesser et al. proved the existence of an activating HRAS mutation as the cause of this syndrome. A higher incidence of cancer has been observed in germline RASophaties. Furthermore, up to 30% of human cancers show dysregulation of the Ras-Raf-MEK-ERK pathways. In our patient, a HRAS mosaic mutation explains not only the cutaneous but also the extracutaneous manifestations. To our knowledge this is the first described case of PPK in which the existence of a HRAS mosaic mutation is the confirmed cause of rhabdomyosarcoma. Besides the HRAS 37G>C mutation has never been related to any type of rhabdomyosarcoma. Mosaicisms could be underdiagnosed causes of childhood tumours. As dermatologists we stand on a privileged position for the detection of these alterations.

This article is protected by copyright. All rights reserved.

http://ift.tt/2Ek1YIx

Patient, Surgeon, and Anesthesiologist Satisfaction: Who has the Priority?

No abstract available

http://ift.tt/2sos0F1

Acquired Central Hypoventilation Syndrome Unmasked by Propofol Sedation

No abstract available

http://ift.tt/2Ezh3Fl

Neurogenic Pulmonary Edema and Stunned Myocardium in a Patient With Meningioma: A Heart-Brain Cross Talk

No abstract available

http://ift.tt/2sqb0hC

Does needle biopsy cause an increased risk of extracapsular extension in the diagnosis of metastatic lymph node in melanoma?

Abstract

Background

Needle biopsy is a rapid, reliable, and reproducible procedure for histological confirmation of metastatic melanoma localization. Nonetheless, this procedure presents a theoretical risk of a mechanical weakening of the lymph node capsule with perinodal tumor seeding. The objective of the study was to evaluate the incidence of extracapsular extension after needle biopsy in comparison with surgical adenectomy in patients suspected of metastatic lymph node of melanoma.

Methods

We conducted a retrospective study of 1056 patients who underwent lymphadenectomy for melanoma between 2000 and 2016 in our unit. Sixty-nine patients were clinically and/or radiologically suspected of metastatic lymph node of melanoma. Patients were divided according to external lymph node biopsy or surgical adenectomy before lymphadenectomy. The primary endpoint was the histopathological identification of extracapsular extension in analyzed lymph nodes.

Results

The two populations were comparable except for the mitotic index, which was more frequently > 1/mm² in the group with surgical adenectomy (P = 0.005). The proportion of extracapsular extension was significantly greater in the needle biopsy group (28/37) than in patients who underwent surgical adenectomy (14/32) (P = 0.0067; OR = 4 [95% CI: 1.4–11]).

Conclusion

Our results suggest an increased risk of extracapsular extension after external lymph node biopsy in cases of suspicion of metastatic lymph node of melanoma. Thus, this encourages us to prefer surgical adenectomy in patients with suspected adenopathy accessible surgically. In other cases, needle biopsy should be carried out under radiological guidance using devices limiting tumor seeding.

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Issue Information - TOC

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Erratum

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The clinical value of HPV E6/E7 and STAT3 mRNA detection in cervical cancer screening

Publication date: Available online 11 February 2018
Source:Pathology - Research and Practice
Author(s): Yibing Fan, Zongji Shen
ObjectiveTo explore the value of human papillomavirus (HPV) E6/E7 and signal transducer and activator of transcription 3 (STAT3) mRNA detection in the screening of cervical lesions.Methods192 patients with abnormal ThinPrep cytology test (TCT) results and/or high-risk HPV infection were screened to identify possible cervical lesions in cases. Diagnoses were confirmed by histopathology. Fluorescence in situ hybridization (FISH) was performed to detect and qualify the mRNAs of HPV E6/E7, STAT3, and Survivin in cervical exfoliated cells. In addition, the performance of separate and combined mRNA detection methods were compared with TCT, HR-HPV DNA schemes respectively.Results1. Compared with HPVE6/E7 and STAT3 mRNA methods, Survivin mRNA assay had poor specificity (Sp), Youden index (YI) and concordance rate. 2. HPV E6/E7, STAT3, and STAT3 + HR-HPV methods had the best Sp, concordance rate and positive predictive value (PPV) for cervical lesions screening and atypical squamous cells of undetermined significance (ASCUS) triage. For screening of high grade squamous intraepithelial lesions or greater (HSILs + ), no difference was observed in the Se of mRNA detection methods in comparison with that of TCT, HR-HPV and TCT + HR-HPV, whereas the false positive rate (FPR) decreased by 41.48%/55.99%/17.19% and the colposcopy referral rate reduced by about 20.00%/25.00%/11.17%. For triage of women with ASCUS, no difference was observed in the Se of mRNA detection methods as compared to that of HR-HPV (χ² = 1.05, P> 0.75), while the FPR decreased by 45.83%/37.50%/41.66% and the colposcopy referral rate reduced by 32.42%/22.60%/25.28%, respectively. The Se, YI, and PPV of the combined methods increased in comparison to each method alone. 3. Compared with the TCT + HR-HPV method, HPV E6/E7 + STAT3 method had perfect Sp (95.92%) and PPV (95.40%) for screening HSILs+, the FPR and colposcopy referral rate decreased by 31.06% and 22.48% respectively.Conclusions1. The expression of HPV E6/E7 and STAT3 mRNA confirmed using FISH assay is expected to be a new method and molecular marker for cervical lesions screening. Survivin mRNA was excluded due to its poor performance. 2. HPV E6/E7, STAT3, and STAT3 +HR-HPV assays could be new approaches for cervical cancer screening and ASCUS triage, and the efficiency of combined screening program was better than that of a separate one. 3. HPV E6/E7 + STAT3 regimen is expected to be a diagnostic strategy for cervical lesions.



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Colchicine in dermatology: A review

Abstract

Colchicine is an anti-inflammatory agent that has been used for decades for the treatment of various diseases including gout, familial Mediterranean fever and pericarditis and in recent years for dermatological indications including chronic urticaria, cutaneous vasculitis and psoriasis. Despite its efficacy in various cutaneous diseases, the use of colchicine may be limited by concerns over its side-effects and the potential for toxicity. This article reviews the current literature on the pharmacology of colchicine and its clinical applications in dermatology.

http://ift.tt/2nSAMWX

Colchicine in dermatology: A review

Abstract

Colchicine is an anti-inflammatory agent that has been used for decades for the treatment of various diseases including gout, familial Mediterranean fever and pericarditis and in recent years for dermatological indications including chronic urticaria, cutaneous vasculitis and psoriasis. Despite its efficacy in various cutaneous diseases, the use of colchicine may be limited by concerns over its side-effects and the potential for toxicity. This article reviews the current literature on the pharmacology of colchicine and its clinical applications in dermatology.

http://ift.tt/2nSAMWX

Dystrophic calcinosis cutis within burns, successfully treated with excision and secondary intention wound healing

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Dystrophic calcinosis cutis within burns, successfully treated with excision and secondary intention wound healing

http://ift.tt/2sl5Fby

Is spinal anaesthesia in young infants really safer and better than general anaesthesia?

Purpose of review Concerns regarding the potential neurotoxic effects of general anaesthesia have seen resurgence in awake spinal anaesthesia in neonates and infants. This review includes recently published data from a large prospective randomized controlled trial with view to determining if spinal anaesthesia is safer and better than general anaesthesia in this population. Recent findings Compared with general anaesthesia, spinal anaesthesia results in less haemodynamic instability and fewer early (

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Acute pain management in children: challenges and recent improvements

Purpose of review The evidence regarding the efficacy of analgesics available to guide postoperative pain treatment in pediatric patients is limited. Opioid medications are very often an important component of pediatric postoperative pain treatment but have been associated with perioperative complications. We will focus on initiatives aiming to provide effective treatment minimizing the use of opioids and preventing the long-term consequences of pain. Recent findings Interpatient variability in postoperative pain is currently managed by applying protocols or by trial and error, thus often leading to patients being either undertreated or overtreated. Few evidence-based reports are available to guide the use of opioid medications in children, including the prescription of opioids after hospital discharge. Using combinations of nonopioid analgesics in a multimodal approach may limit the need for opioids, thus decreasing the risk of toxicity and dose-related side effects. There is a lack of adequate research in this field, and more specifically on identifying which patient is at higher risk of poor postoperative pain management. Summary Treatment options have evolved in recent years, including the combinations of multimodal regimens and regional anesthetic techniques. Using combinations of nonopioid analgesics in a multimodal approach may limit the need for opioids. Correspondence to Pablo M. Ingelmo, MD, Department of Anesthesia, Montreal Children's Hospital, B.04.2427, 1001 Boulevard Decarie, Montreal, QC, Canada H4A3J1. Tel: +1 514 412 4448; e-mail: pablo.ingelmo@mcgill.ca Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Intensive care practitioner: I forgot half the things I learned and the other half seems to be all wrong!

No abstract available

http://ift.tt/2spwX0d

Long-term neurocognitive outcomes following surgery and anaesthesia in early life

Purpose of review Repeated controversial and alarming statements of the potential dangers of anaesthetic agents on neurological outcomes in children continue to be issued based primarily on preclinical studies. This review assesses the current evidence of laboratory and clinical data and identifies areas of concerns. Recent findings Published animal and laboratory data consistently indicate that prolonged and excessive use of anaesthetic agents can lead to morphological changes and neurocognitive impairment in animals without a clear cut-off age or a superiority of one technique over another. Retrospective human studies and prospective clinical trials indicate that short exposures to anaesthesia and surgery are safe and have no effect on long-term neurological outcomes. Small and consistent continuing improvements in the perioperative period (aggregation of marginal gains) will impact on long-term neurological morbidity in humans. Summary It is biologically plausible that anaesthetic agents may induce structural changes during mammalian brain development and beyond. However, in the absence of alternatives the impact of the choice of anaesthetic drugs on long-term neurocognitive outcomes is almost certainly to be of limited relevance in humans. The underlying disease processes, surgical intervention, and trauma as well as other known perioperative factors more significantly affect these outcomes. Correspondence to Tom G. Hansen, MD, PhD, Department of Anaesthesia & Intensive Care – Paediatric Section, Odense University Hospital, 5000 Odense C, Denmark. Tel: +45 6541 3812; fax: +45 6611 3415; e-mail: tomghansen@dadlnet.dk Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Non-enhanced MRI in combination with color Doppler flow imaging for improving diagnostic accuracy of parotid gland lesions

Abstract

Purpose

To determine the value of non-enhanced MRI in combination with color Doppler flow imaging (CDFI) for differentiating malignant parotid tumors from benign ones.

Methods

This retrospective study analyzed 51 parotid gland lesions (39 benign and 12 malignant) in 51 patients who underwent preoperative CDFI as well as non-enhanced MRI including T₁-weighted, T₂-weighted, and diffusion-weighted imaging (DWI). Degrees of intratumor vascularity were categorized into four grades basing on CDFI findings. The relationships between the lesion and its adjacent external carotid artery and retromandibular vein were inspected on T₁-weighted and T₂-weighted images. Apparent diffusion coefficient (ADC) values were calculated from diffusion-weighted images, and were used to classify the parotid gland lesions with and without reference to the CDFI findings. The classification results were compared using the McNemar test. Sensitivity, specificity, and accuracy percentages were calculated when the non-enhanced MRI/CDFI findings were used to differentiate benign lesions from malignant ones.

Results

The diagnostic accuracy (96.1 vs 82.4%) was significantly improved when ADCs were used together with CDFI findings for classifying parotid gland lesions compared to when ADCs were used alone. Pleomorphic adenomas had the highest ADCs. The ADC thresholds were 1.425 × 10⁻³ mm²/s for differentiating pleomorphic adenomas from carcinomas, 0.999 × 10⁻³ mm²/s for differentiating pleomorphic adenomas from other benign lesions, and 0.590 × 10⁻³ mm²/s for differentiating benign lesions other than pleomorphic adenomas from lymphomas.

Conclusion

Combining CDFI with non-enhanced MRI can improve the diagnostic accuracy of MRI for classifying parotid gland lesions.

http://ift.tt/2EipIZn

Strain hardening reduces energy absorption efficiency of austenitic stainless steel foams while porosity does not

Publication date: 5 April 2018
Source:Materials & Design, Volume 143
Author(s): Ali Can Kaya, Paul Zaslansky, Mehmet Ipekoglu, Claudia Fleck
Strain hardening significantly affects the mechanical function of steel foams. We compare hardening and failure of two commercially available austenitic stainless steel foams (316L and 310) spanning strut porosities of 9.4 to 14.4%. Damage is correlated with strut microstructure and geometry, combining in-situ quasi-static compression testing in the SEM, 3D-evaluation by synchrotron μCT and bending simulations. We provide an analytical model for the experimentally observed strain hardening. Upon compression, 316L steel foams exhibit a plateau regime of continuously increasing stress due to the hardening effect, whereas 310 steel foams show almost constant plateau stress. This is explained by the much less ductile behaviour of the 310 steel foam struts as compared to 316L steel foam struts. Finite element modelling suggests that significant stress concentrations develop around microporosities in the 310 struts. Due to its finer and less porous microstructure, the 316L foam exhibits a larger energy absorption capacity than the 310 foams. This results in distinctly different efficiency-strain curves. However, up to about 25% strain, the efficiency values are surprisingly similar. Thus, modification of microstructure and/or pore micro-geometry can be used to optimise the stress-strain response to achieve the desired energy absorption property of steel foams.

Graphical abstract

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Dexmedetomidine as a part of general anaesthesia for caesarean delivery in patients with pre-eclampsia: Efficacy and foetal outcome a randomised double-blinded trial

BACKGROUND During general anaesthesia, endotracheal intubation of patients with pre-eclampsia causes stimulation of the sympathetic nervous system and catecholamine release, which may lead to maternal and neonatal complications. OBJECTIVE To attenuate both the stress response and the haemodynamic response to tracheal intubation in patients with pre-eclampsia. DESIGN A randomised, double-blind, controlled study. SETTING Single University Hospital. PATIENTS Sixty patients aged 18 to 45 years with pre-eclampsia receiving general anaesthesia for caesarean section. INTERVENTIONS The patients were randomly allocated to three groups. Groups D1and D2 received an infusion of dexmedetomidine 1 μg kg−1 over the 10 min before induction of general anaesthesia, then 0.4 and 0.6 μg kg−1 h−1 dexmedetomidine, respectively. Group C received equivalent volumes of 0.9% saline. MAIN OUTCOME MEASURES The primary outcome was the effect of dexmedetomidine on mean arterial blood pressure measured before induction of general anaesthesia at 1 and 5 min after intubation, and then every 5 min until 10 min after extubation. The secondary outcomes were blood glucose and serum cortisol (measured before induction of general anaesthesia, and at 1 and 5 min after intubation), postoperative visual analogue pain scores, time to first request for analgesia, the total consumption of analgesia, Ramsay sedation score, maternal and placental vein blood serum levels of dexmedetomidine and neonatal Apgar score at 1 and 5 min. RESULTS At all assessment times, the mean arterial pressures were significantly lower in the dexmedetomidine groups than in the control group. Compared with group C, the heart rate was significantly lower in both groups D1 and D2. In group D2, the heart rate was lower than in group D1. Serum glucose and cortisol were significantly higher in the controls than in either group D1 or D2. Group D2 patients were significantly more sedated on arrival in the recovery room followed by D1. Time to first analgesia was significantly longer in groups D2 and D1 than in group C, and the visual analogue pain scores were significantly lower in groups D1 and D2 than in group C at 1, 2, 3 and 5 h. Total morphine consumption was significantly lower in groups D1 and D2 than in the control group. There was no difference in Apgar scores across the three groups despite significantly higher dexmedetomidine concentrations in group D2 (both maternal and placental vein) than in group D1. CONCLUSION Administration of dexmedetomidine in doses 0.4 and 0.6 μg kg−1 h−1 was associated with haemodynamic and hormonal stability, without causing significant adverse neonatal outcome. TRIAL REGISTRATION Pan African Clinical Trial Registry (PACTR201706002303170), (www.pactr.org). Correspondence to Ashraf M. Eskandr, MD, Department of Anesthesia, ICU and Pain Therapy, Faculty of Medicine, Menoufiya University, 3 Yassin Abd-Elghafar Street, Shibin El-koom, Egypt E-mail: ameskandr@yahoo.com © 2018 European Society of Anaesthesiology

http://ift.tt/2EjETBM

Low anaesthetic waste gas concentrations in postanaesthesia care unit: A prospective observational study

BACKGROUND Volatile anaesthetics are a potential hazard during occupational exposure, pregnancy or in individuals with existing disposition to malignant hyperthermia. Anaesthetic waste gas concentration in postanaesthesia care units (PACU) has rarely been investigated. OBJECTIVE(S) The current study aims to assess concentrations of volatile anaesthetics in relation to room size, number of patients and ventilator settings in different PACUs. DESIGN A prospective observational study. SETTING Two different PACUs of the Hannover Medical School (Hannover, Germany) were evaluated in this study. The rooms differed in dimensions, patient numbers and room ventilation settings. PATIENTS During the observation period, sevoflurane anaesthesia was performed in 65 of 140 patients monitored in postanaesthesia unit one and in 42 of 70 patients monitored in postanaesthesia unit two. MAIN OUTCOME MEASURES Absolute trace gas room concentrations of sevoflurane measured with a compact, closed gas loop high-resolution ion mobility spectrometer. RESULTS Traces of sevoflurane could be detected in 805 out of 970 samples. Maximum concentrations were 0.96 ± 0.20 ppm in postanaesthesia unit one, 0.82 ± 0.07 ppm in postanaesthesia unit two. Median concentration was 0.12 (0.34) ppm in postanaesthesia unit one and 0.11 (0.28) ppm in postanaesthesia unit two. CONCLUSION Low trace amounts of sevoflurane were detected in both PACUs equipped with controlled air exchange systems. Occupational exposure limits were not exceeded. Correspondence to Dr. Sebastian Heiderich, MD, Clinic of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany E-mail: heiderich.sebastian@mh-hannover.de © 2018 European Society of Anaesthesiology

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Low perfusion pressure is associated with renal tubular injury in infants undergoing cardiac surgery with cardiopulmonary bypass: A secondary analysis of an observational study

BACKGROUND Earlier work on adults undergoing surgery with cardiopulmonary bypass suggests that there is a close relationship between the lower limit of the cerebral and renal autoregulation pressures. Although cerebral autoregulation during bypass in infants has been extensively investigated, the impact of bypass on kidney function is not well known. It is, nevertheless, acknowledged that the main pathophysiological process involved in cardiac surgery-related kidney damage is tubular injury, and that urine neutrophil gelatinase-associated lipocaline (uNGAL) is a reliable biomarker of injury. OBJECTIVE To identify the most predictive bypass variable for the measurement of renal injury, its threshold value and the most predictive time below that threshold. DESIGN Observational study linking electronically recorded bypass perfusion pressure and oxygen delivery rate with intra-operative uNGAL excretion. Variations in bypass variables were accounted for by their excursions below several thresholds. SETTING French tertiary referral paediatric cardiac centre. PATIENTS A total of 72 infants in whom uNGAL was measured within 1 h of bypass. INTERVENTIONS None. MAIN OUTCOME MEASURE Renal injury, identified by a high creatinine normalised uNGAL concentration (>21.2 μg mmol−1). RESULTS At the end of bypass, 43.75% of infants had high uNGAL. A more than 40% pressure drop below the normal age-standardised mean arterial pressure was associated with high uNGAL. Receiver operating curve [interquartile range] areas were 0.626 [0.501 to 0.752] for a more than 40% drop, and 0.679 [0.555 to 0.804] for a more than 50% drop. A more than 40% pressure drop for 19.5 min provided a 0.65 negative predictive value for high uNGAL, and a more than 50% pressure drop for 5.4 min provided a 0.67 negative predictive value. The link between uNGAL and oxygen delivery rate was negligible. CONCLUSION Maintaining the perfusion pressure above 60% of the normal age-standardised mean arterial pressure may provide an effective renal protective strategy. TRIAL REGISTRATION Registered on October 11, 2010, ClinicalTrials.gov Identifier: NCT01219998. Correspondence to Mirela Bojan, MD, PhD, Department of Anaesthesiology and Critical Care, Necker-Enfants Malades University Hospital, Assistance Publique – Hôpitaux de Paris, 149, rue de Sèvres, 75743 Paris, France Tel: +33 171396663; e-mail: mirela.bojan@nck.aphp.fr © 2018 European Society of Anaesthesiology

http://ift.tt/2Ejad3I

Dexmedetomidine as a part of general anaesthesia for caesarean delivery in patients with pre-eclampsia: Efficacy and foetal outcome a randomised double-blinded trial

BACKGROUND During general anaesthesia, endotracheal intubation of patients with pre-eclampsia causes stimulation of the sympathetic nervous system and catecholamine release, which may lead to maternal and neonatal complications. OBJECTIVE To attenuate both the stress response and the haemodynamic response to tracheal intubation in patients with pre-eclampsia. DESIGN A randomised, double-blind, controlled study. SETTING Single University Hospital. PATIENTS Sixty patients aged 18 to 45 years with pre-eclampsia receiving general anaesthesia for caesarean section. INTERVENTIONS The patients were randomly allocated to three groups. Groups D1and D2 received an infusion of dexmedetomidine 1 μg kg−1 over the 10 min before induction of general anaesthesia, then 0.4 and 0.6 μg kg−1 h−1 dexmedetomidine, respectively. Group C received equivalent volumes of 0.9% saline. MAIN OUTCOME MEASURES The primary outcome was the effect of dexmedetomidine on mean arterial blood pressure measured before induction of general anaesthesia at 1 and 5 min after intubation, and then every 5 min until 10 min after extubation. The secondary outcomes were blood glucose and serum cortisol (measured before induction of general anaesthesia, and at 1 and 5 min after intubation), postoperative visual analogue pain scores, time to first request for analgesia, the total consumption of analgesia, Ramsay sedation score, maternal and placental vein blood serum levels of dexmedetomidine and neonatal Apgar score at 1 and 5 min. RESULTS At all assessment times, the mean arterial pressures were significantly lower in the dexmedetomidine groups than in the control group. Compared with group C, the heart rate was significantly lower in both groups D1 and D2. In group D2, the heart rate was lower than in group D1. Serum glucose and cortisol were significantly higher in the controls than in either group D1 or D2. Group D2 patients were significantly more sedated on arrival in the recovery room followed by D1. Time to first analgesia was significantly longer in groups D2 and D1 than in group C, and the visual analogue pain scores were significantly lower in groups D1 and D2 than in group C at 1, 2, 3 and 5 h. Total morphine consumption was significantly lower in groups D1 and D2 than in the control group. There was no difference in Apgar scores across the three groups despite significantly higher dexmedetomidine concentrations in group D2 (both maternal and placental vein) than in group D1. CONCLUSION Administration of dexmedetomidine in doses 0.4 and 0.6 μg kg−1 h−1 was associated with haemodynamic and hormonal stability, without causing significant adverse neonatal outcome. TRIAL REGISTRATION Pan African Clinical Trial Registry (PACTR201706002303170), (www.pactr.org). Correspondence to Ashraf M. Eskandr, MD, Department of Anesthesia, ICU and Pain Therapy, Faculty of Medicine, Menoufiya University, 3 Yassin Abd-Elghafar Street, Shibin El-koom, Egypt E-mail: ameskandr@yahoo.com © 2018 European Society of Anaesthesiology

http://ift.tt/2EjETBM

Low anaesthetic waste gas concentrations in postanaesthesia care unit: A prospective observational study

BACKGROUND Volatile anaesthetics are a potential hazard during occupational exposure, pregnancy or in individuals with existing disposition to malignant hyperthermia. Anaesthetic waste gas concentration in postanaesthesia care units (PACU) has rarely been investigated. OBJECTIVE(S) The current study aims to assess concentrations of volatile anaesthetics in relation to room size, number of patients and ventilator settings in different PACUs. DESIGN A prospective observational study. SETTING Two different PACUs of the Hannover Medical School (Hannover, Germany) were evaluated in this study. The rooms differed in dimensions, patient numbers and room ventilation settings. PATIENTS During the observation period, sevoflurane anaesthesia was performed in 65 of 140 patients monitored in postanaesthesia unit one and in 42 of 70 patients monitored in postanaesthesia unit two. MAIN OUTCOME MEASURES Absolute trace gas room concentrations of sevoflurane measured with a compact, closed gas loop high-resolution ion mobility spectrometer. RESULTS Traces of sevoflurane could be detected in 805 out of 970 samples. Maximum concentrations were 0.96 ± 0.20 ppm in postanaesthesia unit one, 0.82 ± 0.07 ppm in postanaesthesia unit two. Median concentration was 0.12 (0.34) ppm in postanaesthesia unit one and 0.11 (0.28) ppm in postanaesthesia unit two. CONCLUSION Low trace amounts of sevoflurane were detected in both PACUs equipped with controlled air exchange systems. Occupational exposure limits were not exceeded. Correspondence to Dr. Sebastian Heiderich, MD, Clinic of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany E-mail: heiderich.sebastian@mh-hannover.de © 2018 European Society of Anaesthesiology

http://ift.tt/2EY3yx2

Low perfusion pressure is associated with renal tubular injury in infants undergoing cardiac surgery with cardiopulmonary bypass: A secondary analysis of an observational study

BACKGROUND Earlier work on adults undergoing surgery with cardiopulmonary bypass suggests that there is a close relationship between the lower limit of the cerebral and renal autoregulation pressures. Although cerebral autoregulation during bypass in infants has been extensively investigated, the impact of bypass on kidney function is not well known. It is, nevertheless, acknowledged that the main pathophysiological process involved in cardiac surgery-related kidney damage is tubular injury, and that urine neutrophil gelatinase-associated lipocaline (uNGAL) is a reliable biomarker of injury. OBJECTIVE To identify the most predictive bypass variable for the measurement of renal injury, its threshold value and the most predictive time below that threshold. DESIGN Observational study linking electronically recorded bypass perfusion pressure and oxygen delivery rate with intra-operative uNGAL excretion. Variations in bypass variables were accounted for by their excursions below several thresholds. SETTING French tertiary referral paediatric cardiac centre. PATIENTS A total of 72 infants in whom uNGAL was measured within 1 h of bypass. INTERVENTIONS None. MAIN OUTCOME MEASURE Renal injury, identified by a high creatinine normalised uNGAL concentration (>21.2 μg mmol−1). RESULTS At the end of bypass, 43.75% of infants had high uNGAL. A more than 40% pressure drop below the normal age-standardised mean arterial pressure was associated with high uNGAL. Receiver operating curve [interquartile range] areas were 0.626 [0.501 to 0.752] for a more than 40% drop, and 0.679 [0.555 to 0.804] for a more than 50% drop. A more than 40% pressure drop for 19.5 min provided a 0.65 negative predictive value for high uNGAL, and a more than 50% pressure drop for 5.4 min provided a 0.67 negative predictive value. The link between uNGAL and oxygen delivery rate was negligible. CONCLUSION Maintaining the perfusion pressure above 60% of the normal age-standardised mean arterial pressure may provide an effective renal protective strategy. TRIAL REGISTRATION Registered on October 11, 2010, ClinicalTrials.gov Identifier: NCT01219998. Correspondence to Mirela Bojan, MD, PhD, Department of Anaesthesiology and Critical Care, Necker-Enfants Malades University Hospital, Assistance Publique – Hôpitaux de Paris, 149, rue de Sèvres, 75743 Paris, France Tel: +33 171396663; e-mail: mirela.bojan@nck.aphp.fr © 2018 European Society of Anaesthesiology

http://ift.tt/2Ejad3I

Ethosuximide-induced Stevens–Johnson syndrome: Beneficial effect of early intervention with high-dose corticosteroid therapy

Abstract

We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens–Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.

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Case of deep vein thrombosis in a patient with advanced malignant melanoma treated with dabrafenib and trametinib

http://ift.tt/2Ej2XJ0

Immunocryosurgery as monotherapy for lentigo maligna or combined with surgical excision for lentigo maligna melanoma

Abstract

The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area. Subsequently, a combined treatment with topical imiquimod and cryosurgery was performed. The LM patient received immunocryosurgery directly. All of them were free of local and systemic disease at 48, 42 and 41 months after discontinuation of therapy. We consider that immunocryosurgery is an alternative option for LM or even for LMM (after removal of the invasive tissue with narrow margins) in poor surgical candidates, with good therapeutic, functional and cosmetic results.

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Benign cephalic histiocytosis: A case with infiltration of CD1a-positive langerin-negative cells

http://ift.tt/2EhYmqB

Electromyographic findings in sporadic inclusion body myositis

Publication date: Available online 11 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Monika Nojszewska, Malgorzata Gawel, Biruta Kierdaszuk, Janusz Sierdziński, Elżbieta Szmidt-Sałkowska, Andrzej Seroka, Anna M. Kamińska, Anna Kostera-Pruszczyk
IntroductionClinically oriented diagnostic criteria can be as specific for diagnosis of sporadic inclusion body myositis (sIBM) as pathological criteria, especially at the time of presentation. EMG may provide an convincing proof that a muscle biopsy should be performed.Aimsto compare the EMG results in patients with sIBM divided into subgroups based on the newest ENMC criteria for sIBM and to obtain the utility of EMG in the diagnostic process at the time of presentation.MethodsWe retrospectively analysed 16 patients with sIBM for motor unit action potential (MUAP) morphology as well as occurrence and distribution of abnormal spontaneous activity (SA) in muscles.ResultsAbnormal SA was recorded in 62.5% of sIBM patients. We found statistically significant differences between subgroups in the incidence of polyphasic MUAPs and high amplitude outliers which were more commonly seen in the "clinico-pathologically defined sIBM". Duration of MUAP in the tibialis anterior was significantly shorter in "probable sIBM". Discussion"Pseudo-neurogenic" MUAPs, mainly in lower limb muscles, are more commonly seen in "clinico-pathologically defined sIBM" while myopathic MUAPs with prominent abnormal SA are recorded in patients diagnosed with "probable sIBM". Both EMG patterns may be suggestive of sIBM and be an indication for further diagnosis.



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Radiation Pneumonitis in Pediatric Hodgkin Lymphoma Patients receiving Radiotherapy to the Chest

Publication date: Available online 4 February 2018
Source:Practical Radiation Oncology
Author(s): Gary D. Lewis, Jennifer E. Agrusa, Bin S. Teh, Maria M. Gramatges, Viral Kothari, Carl E. Allen, Arnold C. Paulino
PurposeThe purpose of this study is to determine the incidence of radiation pneumonitis (RP) in children receiving radiotherapy (RT) for Hodgkin lymphoma (HL).Patients/MethodsA retrospective chart review was conducted of pediatric HL patients who received multiagent chemotherapy followed by RT to any part of the chest. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to determine the RP grade. Parameters analyzed included gender, age, bleomycin dose, and RT dosimetric variables such as mean lung dose (MLD), mean individual (right versus left) lung dose or iMLD, V5 to V25 and individual (i) lung V5 to V25.ResultsFrom 2008-2016, 54 children with HL received RT to the chest and had follow-up and dosimetry information. All patients received induction chemotherapy; the most common regimen was ABVE-PC based chemotherapy (n = 48). All received a prescribed dose of 21 Gy in 14 fractions. Median follow-up from completion of RT was 39.5 months. Three of 54 patients (5.6%) or 3 of 108 (2.8%) lungs developed RP; two lungs had Grade 1 while one had Grade 2 RP. RP was seen only in patients with MLD > 12.4 Gy (p = 0.009), V5 > 66% (p = 0.033), V10 >55% (p = 0.015), V15 >45% (p = 0.005) and V20 > 32% (p = 0.007). Likewise, RP was only seen in lungs with iMLD > 13.8 Gy, iV5 > 75% (p =0.02), iV10 > 64% (p = 0.02), iV15 > 47% (< 0.005), and iV20 >34% (p = 0.003).ConclusionsRP in pediatric HL patients is an uncommon complication. MLD, iMLD, V5-V20 and iV5-iV20 correlated with RP.



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Design and Evaluation of a Safety-Centered User Interface for Radiation Therapy

Publication date: Available online 4 February 2018
Source:Practical Radiation Oncology
Author(s): Ashleigh P. Shier, Plinio P. Morita, Colleen Dickie, Mohammad Islam, Catherine Burns, Joseph A Cafazzo
PurposeAs radiotherapy treatment grows more complex over time, treatment delivery has become more susceptible to adverse events and patient safety risks due to use error. The radiotherapy monitoring and treatment delivery user interface explored in this study was redesigned using ecological interface design, a human factors engineering method, and evaluated to improve treatment safety.Methods and MaterialsAn initial design concept was created based on previously completed analysis, and informally evaluated in focus groups with radiation therapists. Sixteen newly graduated radiation therapists used both the redesigned and current system in a usability test to determine if the redesigned system better supported detection of errors.ResultsThe redesigned system successfully improved the error detection rate of two errors, wrong treatment volume and wrong treatment site (p < 0.03 and p < 0.01, respectively). It also improved Level 2 and Level 3 situation awareness, i.e. comprehension of the meaning of the information and the projection of the behavior of the technology (p < 0.01 and p < 0.01 respectively), and achieved a higher user satisfaction.ConclusionsThe ecological interface design approach was found to be effective in redesigning a radiotherapy treatment delivery interface. Radiation therapists were able to deliver simulated radiation therapy with a higher rate of error detection, improved higher-level situation awareness, and participants preferred the redesigned interface to the current interface. Overall, the redesigned interface improved the radiation therapists' system understanding and ability to detect errors that affect patient safety.



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Impact of timing of radiotherapy on outcomes in atypical meningioma: a clinical audit

Publication date: Available online 4 February 2018
Source:Practical Radiation Oncology
Author(s): Sidharth Pant, Raees Tonse, Sadhana Kannan, Aliasgar Moiyadi, Prakash Shetty, Sridhar Epari, Ayushi Sahay, Goda Jayant Sastri, Rakesh Jalali, Tejpal Gupta
BackgroundRole of early adjuvant radiotherapy (RT) in patients with atypical meningioma remains controversial.PurposeTo report the impact of timing of RT on outcomes in atypical meningioma.MethodsPatients of atypical meningioma were identified through electronic search of institutional database. Following surgery, RT was delivered either in upfront adjuvant setting (early adjuvant RT) or after recurrence/progression (salvage RT).ResultsThere were 51 patients in early adjuvant RT group and 30 patients in salvage RT group. Six of 51 (12%) patients in early adjuvant RT group recurred/progressed compared to 34 of 35 (97%) patients kept on observation after initial surgery. Thirty of these 34 patients received salvage RT, mostly after re-excision. Twelve of 30 (40%) patients recurred/progressed after salvage RT, compared to 6 of 51 (12%) patients after early adjuvant RT (p=0.003). Post-RT 5-year progression-free survival was significantly better for early adjuvant RT compared to salvage RT (69% vs 28%, log-rank p<0.001).ConclusionsWithin the limitations of any retrospective analysis, upfront early adjuvant RT can significantly reduce the risk of local recurrence/progression in atypical meningiomas compared to initial observation. A sizeable proportion of patients who are observed initially recur/progress over time necessitating salvage therapy. However, re-excision followed by salvage RT may not be as effective as early adjuvant RT.



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Management of Paranasal Sinus Metastasis by Percutaneous CT guided Permanent Seed Brachytherapy: Technical Report

Publication date: Available online 1 February 2018
Source:Practical Radiation Oncology
Author(s): Stephen Doggett, Shigeru Chino, Todd Lempert, Kunal Sidhar




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Pre-Operative Contralateral Radiation Lung Dose is Associated with Post-Operative Pulmonary Toxicity in Patients with Locally-Advanced Non-Small Cell Lung Cancer Treated with Trimodality Therapy

Publication date: Available online 31 January 2018
Source:Practical Radiation Oncology
Author(s): Wenji Guo, Xuan Hui, Salem Alfaifi, Lori Anderson, Scott Robertson, Russell Hales, Chen Hu, Todd McNutt, Stephen Broderick, Jarushka Naidoo, Richard Battafarano, Stephen Yang, K. Ranh Voong
PurposeIn patients with non-small cell lung cancer (NSCLC) who undergo trimodality therapy (chemoradiation followed by surgical resection), it is unknown whether limiting pre-operative radiation dose to the uninvolved lung reduces post-surgical morbidity. This study evaluated whether radiation fall-off dose parameters to the contralateral lung, that is unaffected by NSCLC, are associated with post-operative complications in NSCLC patients treated with trimodality therapy.Methods and materialsWe retrospectively reviewed NSCLC patients who underwent trimodality therapy between March 2008-October 2016, with available restored digital radiation plans. Fischer's exact test was used to assess associations between patient and treatment characteristics and the development of treatment-related toxicity. Spearman's rank correlation was used to measure the strength of association between dosimetric parameters.ResultsForty-six patients were identified who received trimodality therapy with intensity modulated radiation (median 59.4 Gy, range 45-70) and concurrent platinum doublet chemotherapy, followed by surgical resection. The median age was 64.9 years (range 45.6-81.6 years). The median follow-up time was 1.9 years (range 0.3-8.4 years). Twenty-four (52.2%) patients developed any grade pulmonary toxicity and 14 (30.4%) patients developed grade 2+ pulmonary toxicity. There was an increased incidence of any grade pulmonary toxicity in patients with contralateral lung V20≥7% compared to <7% (90%, n=9 versus 41.7%, n=15; p=0.01). Similarly, contralateral lung V10≥20% was associated with an increased rate of any grade pulmonary toxicity compared to V10<20% (80%, n=12 versus 38.7%, n=12; p=0.01). Pneumonectomy/bilobectomy was associated with grade 2+ pulmonary toxicity (p=0.04).ConclusionsPatients who received a higher radiation fall-off dose volume parameter (V20≥7% and V10≥20%) to the contralateral uninvolved lung had a higher incidence of any grade post-operative pulmonary toxicity. Limiting radiation fall-off dose to the uninvolved lung may be an important modifiable radiation parameter in limiting post-operative toxicity in trimodality patients.



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NRG Oncology Medical Physicists’ Manpower Survey Quantifying Support Demands for Multi-Institutional Clinical Trials

Publication date: Available online 4 February 2018
Source:Practical Radiation Oncology
Author(s): James I Monroe, Karan Boparai, Ying Xiao, David Followill, James M Galvin, Eric E Klein, Daniel Low, Jean M Moran, Haoyu Zhong, Jason W Sohn
PurposeA survey was created by XXXX to assess a medical physicists' percent Full Time Equivalent (FTE) contribution to multi-institutional clinical trials. A 2012 ASTRO report, 'Safety Is No Accident', quantified medical physics staffing contributions in FTE Factors for clinical departments. No quantification of FTE effort associated with clinical trials was included.MethodsTo address this lack of information, the XXXX Medical Physics Subcommittee decided to obtain manpower data from the medical physics community to quantify the amount of time medical physicists spent supporting clinical trials. A survey, consisting of sixteen questions, was designed to obtain information regarding physicists' time spent supporting clinical trials. The survey was distributed to medical physicists at 1996 radiotherapy institutions included on the membership rosters of the five NCTN clinical trial groups.ResultsOf the 451 institutions who responded; fifty percent (226) of the respondents reported currently participating in radiotherapy trials. On average, the designated physicist at each institution spent 2.4 hours (SD: 5.5 hours) per week supervising or interacting with clinical trial staff. On average, 1.2 hours (SD: 3.1 hours), 1.8 hours (SD: 3.9 hours), and 0.6 hours (SD: 1.1 hours) per week were spent on trial patient simulations, treatment plan reviews, and maintaining a DICOM server, respectively. For all trial credentialing activities, physicists spent an average of 32 hours (SD: 57.2 hours) yearly. Reading protocols and supporting dosimetrists, clinicians, and therapists took an average of 2.1 hours (SD: 3.4 hours) per week. Physicists also attended clinical trial meetings, on average, 1.2 hours (SD: 1.9 hours) per month.ConclusionOn average, physicist spent a non-trivial total of 9 hours per week (0.21 FTE) supporting an average of 10 active clinical trials. This time commitment indicates the complexity of radiotherapy clinical trials and should be taken into account when staffing radiotherapy institutions.



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Utilizing 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) to define suspected non-enhancing tumor for radiotherapy planning of glioblastoma

Publication date: Available online 31 January 2018
Source:Practical Radiation Oncology
Author(s): Aimee R Hayes, Dasantha Jayamanne, Edward Hsiao, Geoffrey P Schembri, Dale L Bailey, Paul J Roach, Mustafa Khasraw, Allison Newey, Helen R Wheeler, Michael Back
AimTo evaluate the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiotherapy planning for patients diagnosed with glioblastoma (GBM) and presence of suspected non-enhancing tumors compared with standard magnetic resonance imaging (MRI).MethodsPatients with GBM and contrast-enhancing MRI showing regions suspicious of non-enhancing tumor underwent post-operative FET-PET prior to commencing radiotherapy. Two Clinical Target Volumes (CTVs) were created using pre- and post-operative MRI; MRI-FLAIR sequences (CTVFLAIR) and MRI contrast sequences with an expansion on the surgical cavity (CTVSx). FET-PET was used to create Biological Tumor Volumes (BTVs) by encompassing FET avid regions, forming a BTVFLAIR and BTVSx. Volumetric analyses were conducted between CTVs and respective BTVs using Wilcoxon signed-rank tests. The volume increase with addition of FET was analyzed with respect to BTVFLAIR and BTVSx. Presence of focal gadolinium contrast enhancement within previously non-enhancing tumor or within the FET avid region was noted on MRI at one and three months after radiotherapy.ResultsTwenty-six patients were identified retrospectively from our database, of which 24 had demonstrable FET uptake. The median CTVFLAIR, CTVSx, BTVFLAIR and BTVSx was 57.1 cc (range 1.1-217.4), 83.6 cc (range 27.2-275.8), 62.8 cc (range 1.1-307.3) and 94.7 cc (range 27.2-285.5) respectively. When FET-PET was utilized, there was a mean increase in volume from CTVFLAIR to BTVFLAIR by 26.8% and CTVSx to BTVSx by 20.6%. A statistically significant difference was noted on Wilcoxon signed-rank test when assessing volumetric change between CTVFLAIR and BTVFLAIR (P<0.0001) and CTVSx and BTVSx (p<0.0001). Six out of 24 patients (25%), with FET avidity prior to radiotherapy, showed focal gadolinium enhancement within the radiotherapy portal.ConclusionFET-PET may help improve delineation of GBM in cases with a suspected non-enhancing component. This may result in improved radiotherapy target delineation and reduce the risk of potential geographical miss.SummaryWe investigated the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiotherapy planning for patients diagnosed with glioblastoma (GBM) and a suspected non-enhancing tumor compared with standard magnetic resonance imaging (MRI). We performed volumetric analyses between clinical target volumes and respective biological target volumes using Wilcoxon signed-rank tests. In conclusion, FET-PET may help improve delineation of GBM in cases with a suspected non-enhancing component and reduce the risk of potential geographical miss.



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Development of a Virtual Radiation Oncology Clinic for training and simulation of errors in the radiation oncology workflow

Publication date: Available online 12 January 2018
Source:Practical Radiation Oncology
Author(s): TR Willoughby, SL Meeks, P Kelly, T Dvorak, K. Muller, T. Dana, F Bova




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An interactive contouring module improves engagement and interest in radiation oncology among pre-clinical medical students: Results of a randomized trial

Publication date: Available online 12 January 2018
Source:Practical Radiation Oncology
Author(s): Pushpa Neppala, Michael Sherer, Grant Larson, Alex Bryant, Neil Panjwani, James D. Murphy, Erin F Gillespie
PurposeStudies have shown significant gaps in knowledge of radiation therapy among medical students and primary care providers. The goal of this study was to evaluate the impact of an interactive contouring module on knowledge and interest in radiation oncology among pre-clinical medical students.Methods and MaterialsSecond year medical students at *** were randomized to participate in an interactive contouring exercise or watch a traditional didactic lecture on radiation oncology. Participants completed knowledge tests and surveys at baseline, immediately following the exercise, and 3 months later. Statistical analysis included Wilcoxon signed-rank test for pre- and post-test comparisons and Wilcoxon rank sum test for comparison between groups.ResultsForty-three medical students participated in the trial (21 in the didactic group and 22 in the contouring group). Students completing the contouring module demonstrated similar overall knowledge improvement compared to the traditional didactic group (+8.6% vs. +6.6%, NS) but endorsed greater engagement on a 5-point Likert-type scale (3.10 vs 3.76, p=0.02). At 3-month follow-up, there was a non-significant trend toward improved overall knowledge in the contouring group (43% vs. 51%, p=0.10), with a significance difference in a subset of questions on knowledge of the process of radiation therapy as well as side effects (51% vs. 75%, p=0.002). Students in the contouring group demonstrated more interest in pursuing a clinical radiation oncology rotation (2.52 vs 3.27, p=0.01).ConclusionsUse of an interactive contouring module was an effective method to teach pre-clinical medical students about radiation oncology, with no significant difference in knowledge gained compared to a traditional didactic lecture. However, higher engagement among students completing the contouring module led to improved retention of knowledge of radiation side effects and greater interest in radiation oncology. These data suggest a potential benefit of integrating an interactive radiation oncology module into the pre-clinical medical school curriculum.



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Stereotactic body radiotherapy for high-risk prostate cancer: Not ready

Publication date: Available online 12 January 2018
Source:Practical Radiation Oncology
Author(s): Trevor J. Royce, Ronald C. Chen




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On the origin of epileptic High Frequency Oscillations observed on clinical electrodes

Publication date: Available online 11 February 2018
Source:Clinical Neurophysiology
Author(s): Mohamad Shamas, Pascal Benquet, Isabelle Merlet, Mohamad Khalil, Wassim El Falou, Anca NICA, Fabrice Wendling
ObjectiveIn this study we aim to identify the key (patho)physiological mechanisms and biophysical factors which impact the observability and spectral features of High Frequency Oscillations (HFOs).MethodsIn order to accurately replicate HFOs we developed virtual-brain / virtual-electrode simulation environment combining novel neurophysiological models of neuronal populations with biophysical models for the source/sensor relationship. Both (patho)physiological mechanisms (synaptic transmission, depolarizing GABAA effect, hyperexcitability) and physical factors (geometry of extended cortical sources, size and position of electrodes) were taken into account. Simulated HFOs were compared to real HFOs extracted from intracerebral recordings of 2 patients.ResultsOur results revealed that HFO pathological activity is being generated by feed-forward activation of cortical interneurons that produce fast depolarizing GABAergic post-synaptic potentials (PSPs) onto pyramidal cells. Out of phase patterns of depolarizing GABAergic PSPs explained the shape, entropy and spatiotemporal features of real human HFOs.ConclusionsThe terminology "high-frequency oscillation" (HFO) might be misleading as the fast ripple component (200-600Hz) is more likely a "high-frequency activity" (HFA), the origin of which is independent from any oscillatory process.SignificanceNew insights regarding the origins and observability of HFOs along depth-EEG electrodes were gained in terms of spatial extent and 3D geometry of neuronal sources.



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10-10 Electrode Placement System

Publication date: Available online 11 February 2018
Source:Clinical Neurophysiology
Author(s): Marc R. Nuwer




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To warn or not to warn: A reappraisal of brainstem auditory evoked potential warning criteria during surgery

Publication date: Available online 11 February 2018
Source:Clinical Neurophysiology
Author(s): Aatif M. Husain




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A novel antibody-based approach to detect the functional ERCC1-202 isoform

Publication date: Available online 11 February 2018
Source:DNA Repair
Author(s): Mei-Shiue Kuo, Julien Adam, Nicolas Dorvault, Angélique Robin, Luc Friboulet, Jean-Charles Soria, Ken A. Olaussen
ERCC1/XPF endonuclease plays an important role in multiple DNA repair pathways and stands as a potential prognostic and predictive biomarker for cisplatin-based chemotherapy. Four distinct ERCC1 isoforms arising from alternative splicing have been described (201, 202, 203 and 204) but only the 202 isoform is functional in DNA excision repair, when interacting with its obligate partner XPF. Currently, there is no tool to assess specifically the expression of ERCC1-202 due to high sequence homology between the four isoforms. Here, we generated monoclonal antibodies directed against the heterodimer of ERCC1 and its obligate interacting partner XPF by genetic immunization. We obtained three monoclonal antibodies (2C11, 7C3 and 10D10) recognizing specifically the heterodimer ERCC1-202/XPF as well as the ERCC1-204/XPF with no affinity to ERCC1 or XPF monomers. By combining one of these three heterodimer-specific antibodies with a commercial anti-ERCC1 antibody (clone 4F9) unable to recognize the 204 isoform in a proximity ligation assay (PLA), we managed to specifically detect the functional ERCC1-202 isoform. This methodological breakthrough can constitute a basis for the development of clinical tests to evaluate ERCC1 functional proficiency.



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The role of the N-terminal domain of human apurinic/apyrimidinic endonuclease 1, APE1, in DNA glycosylase stimulation

Publication date: Available online 11 February 2018
Source:DNA Repair
Author(s): Olga Kladova, Milena Bazlekowa-Karaban, Sonia Baconnais, Olivier Pietrement, Alexander A. Ishchenko, Bakhyt T. Matkarimov, Olga S. Fedorova, Eric Le Cam, Barbara Tudek, Nikita A. Kuznetsov, Murat Saparbaev
The base excision repair (BER) pathway consists of sequential action of DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease necessary to remove a damaged base and generate a single-strand break in duplex DNA. Human multifunctional AP endonuclease 1 (APE1, a.k.a. APEX1, HAP-1, or Ref-1) plays essential roles in BER by acting downstream of DNA glycosylases to incise a DNA duplex at AP sites and remove 3′-blocking sugar moieties at DNA strand breaks. Human 8-oxoguanine-DNA glycosylase (OGG1), methyl-CpG-binding domain 4 (MBD4, a.k.a. MED1), and alkyl-N-purine-DNA glycosylase (ANPG, a.k.a. Aag or MPG) excise a variety of damaged bases from DNA. Here we demonstrated that the redox-deficient truncated APE1 protein lacking the first N-terminal 61 amino acid residues (APE1-NΔ61) cannot stimulate DNA glycosylase activities of OGG1, MBD4, and ANPG on duplex DNA substrates. Electron microscopy imaging of APE1–DNA complexes revealed oligomerization of APE1 along the DNA duplex and APE1-mediated DNA bridging followed by DNA aggregation. APE1 polymerizes on both undamaged and damaged DNA in cooperative mode. Association of APE1 with undamaged DNA may enable scanning for damage; however, this event reduces effective concentration of the enzyme and subsequently decreases APE1-catalyzed cleavage rates on long DNA substrates. We propose that APE1 oligomers on DNA induce helix distortions thereby enhancing molecular recognition of DNA lesions by DNA glycosylases via a conformational proofreading/selection mechanism. Thus, APE1-mediated structural deformations of the DNA helix stabilize the enzyme–substrate complex and promote dissociation of human DNA glycosylases from the AP site with a subsequent increase in their turnover rate.Significance StatementThe major human apurinic/apyrimidinic (AP) endonuclease, APE1, stimulates DNA glycosylases by increasing their turnover rate on duplex DNA substrates. At present, the mechanism of the stimulation remains unclear. We report that the redox domain of APE1 is necessary for the active mode of stimulation of DNA glycosylases. Electron microscopy revealed that full-length APE1 oligomerizes on DNA possibly via cooperative binding to DNA. Consequently, APE1 shows DNA length dependence with preferential repair of short DNA duplexes. We propose that APE1-catalyzed oligomerization along DNA induces helix distortions, which in turn enable conformational selection and stimulation of DNA glycosylases. This new biochemical property of APE1 sheds light on the mechanism of redox function and its role in DNA repair.

Graphical abstract

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Functional capacity in adults with cerebral palsy: Lower limb muscle strength matters.

Publication date: Available online 10 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jarred G. Gillett, Glen A. Lichtwark, Roslyn N. Boyd, Lee A. Barber
ObjectiveTo investigate the relationship between lower limb muscle strength, passive muscle properties and functional capacity outcomes in adults with cerebral palsy (CP).DesignCross-sectional study.SettingTertiary institution biomechanics laboratory.ParticipantsSample of 33 adults with spastic-type CP with a mean age of 25 (range, 15-51) years; mean ± SD body mass 70.15 ± 21.35 kg; Gross Motor Function Classification System (GMFCS) level I n=20, level II n=13.InterventionsNot applicable.Main Outcome MeasuresSix-minute walk test (6MWT) distance (m); lateral step-up (LSU) test performance (total repetitions); timed up-stairs (TUS) performance (s); maximum voluntary isometric strength of plantar flexors (PF) and dorsiflexors (DF) (Nm.kg^-1); and passive ankle joint and muscle stiffness.ResultsMaximum isometric PF strength independently explained 61% of variance in 6MWT performance; 57% of variance in LSU test performance; and 50% of variance in TUS test performance. GMFCS level was significantly and independently related to all three functional capacity outcomes, and age was retained as a significant independent predictor of LSU, and TUS test performance. Passive medial gastrocnemius muscle fascicle stiffness and ankle joint stiffness were not significantly related to functional capacity measures in any of the multiple regression models.ConclusionsLow isometric PF strength was the most important independent variable related to distance walked on the 6MWT, fewer repetitions on the LSU test, and slower TUS test performance. These findings suggest lower isometric muscle strength contributes to the decline in functional capacity in adults with CP.



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What factors are associated with the recovery of autonomy after a hip fracture? A prospective multicentric cohort study

Publication date: Available online 10 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Mattia Morri, Paolo Chiari, Cristiana Forni, Antonella Orlandi Magli, Domenica Gazineo, Natalia Franchini, Lorenzo Marconato, Tiziana Giamboi, Andrea Cotti
Objectiveto identify the factors associated with recovering autonomy in the activities of daily livingDesignA prospective cohort studySettingThe orthopedic and orthogeriatric departments of 2 regional hospitalsParticipantsPatients 65 years of age or older with a diagnosis of fragility hip fracture. There were 840 eligible patients. Forty-three patients were excluded and 55 were lost. Seven hundred and forty-two consecutive patients was enrolled at the time of hospitalization and 727 at follow-up.Main Outcome MeasuresThe level of autonomy at 4 months was assessed using the ADL scale.ResultsThe score of the ADL scale at 4 months had a median equal to 3 (IQR=5). Half of the population was unable to recover their prefracture autonomy levels. The following were found to be risk factors: increasing age (B= 0.02; p<0.001), an elevated number of comorbidities (B=0.044; p=0.005); a lower level of prefracture autonomy (B=0.087; p<0.001); more frequent use of an anti-decubitus mattress (B=0.211; p<0.001), an increased number of days with disorientation (B=0.002; p=0.012); failure to recover deambulation (B=0.199; p<0.001); an increased number of days with diapers (B=0.003; p<0.001), with a urinary catheter (B=0.03; p<0.001) and with bed rails (B=0.001; p=0.014), and a non-intensive care pathway (B=0,199; p=0,014).ConclusionIn the initial phase, treatment of patients with hip fractures is significantly associated with the functional recovery of autonomy and should be activated starting from those factors which have the possibility of being modified in clinical practice: recovery of deambulation, treatment for disorientation and management of incontinence.



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Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities

Publication date: Available online 10 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Weiming Luo, David Tweedie, Shaunna L. Beedie, Neil Vargesson, William D. Figg, Nigel H. Greig, Michael T. Scerba
A library of 15 novel and heretofore uncharacterized adamantyl and noradamantyl phthalimidines was synthesized and evaluated for neuroprotective and anti-angiogenic properties. Phthalimidine treatment in LPS-challenged cells effected reductions in levels of secreted TNF-α and nitrite relative to basal amounts. The primary SAR suggests nitration of adamantyl phthalimidines has marginal effect on TNF- α activity but promotes anti-nitrite activity; thioamide congeners retain anti-nitrite activity but are less effective reducing TNF- α. Site-specific nitration and thioamidation provided phthalimidine 24, effecting an 88.5% drop in nitrite concurrent with only a 4% drop in TNF- α. Notable anti-angiogenesis activity was observed for 20, 21 and 22.

Graphical abstract

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Synthesis and evaluation of novel dolastatin 10 derivatives for versatile conjugations

Publication date: Available online 11 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Shinya Yokosaka, Akiko Izawa, Chizuka Sakai, Eri Sakurada, Yasuhiro Morita, Yukihiro Nishio
Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC50 < 5.0 nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative structures used in known conjugated drugs. These novel analogs showed excellent potency in a tumor cell proliferation assay, and thus this series of dolastatin 10 analogs is suitable as versatile payloads in conjugated drugs. Insights into the structure-activity relationships of the analogs are also discussed.

Graphical abstract

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Selenite and methylseleninic acid epigenetically affects distinct gene sets in myeloid leukemia: A genome wide epigenetic analysis

Publication date: Available online 10 February 2018
Source:Free Radical Biology and Medicine
Author(s): Prajakta Khalkar, Hani Abdulkadir Ali, Paula Codó, Nuria Díaz Argelich, Anni Martikainen, Mohsen Karimi Arzenani, Sören Lehmann, Julian Walfridsson, Johanna Ungerstedt, Aristi P. Fernandes
Selenium compounds have emerged as promising chemotherapeutic agents with proposed epigenetic effects, however the mechanisms and downstream effects are yet to be studied. Here we assessed the effects of the inorganic selenium compound selenite and the organic form methylseleninic acid (MSA) in a leukemic cell line K562, on active (histone H3 lysine 9 acetylation, H3K9ac and histone H3 lysine 4 tri-methylation, H3K4me3) and repressive (histone H3 lysine 9 tri-methylation, H3K9me3) histone marks by Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq). Both selenite and MSA had major effects on histone marks but the effects of MSA were more pronounced. Gene ontology analysis revealed that selenite affected genes involved in response to oxygen and hypoxia, whereas MSA affected distinct gene sets associated with cell adhesion and glucocorticoid receptors, also apparent by global gene expression analysis using RNA sequencing. The correlation to adhesion was functionally confirmed by a significantly weakened ability of MSA treated cells to attach to fibronectin and linked to decreased expression of integrin beta 1. A striking loss of cellular adhesion was also confirmed in primary patient AML cells. Recent strategies to enhance the cytotoxicity of chemotherapeutic drugs by disrupting the interaction between leukemic and stromal cells in the bone marrow are of increasing interest; and organic selenium compounds like MSA might be promising candidates. In conclusion, these results provide new insight on the mechanism of action of selenium compounds, and will be of value for the understanding, usage, and development of new selenium compounds as anticancer agents.

Graphical abstract

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Accuracy of frozen section in determining meningioma subtype and grade

Publication date: Available online 10 February 2018
Source:Annals of Diagnostic Pathology
Author(s): Richard A. Prayson
Frozen section intraoperative consultation is a well-established means of evaluating brain tumors at the time of surgery. Limitations to the procedure are also well recognized resulting in less than perfect specificity of diagnosis. This study retrospectively reviewed 424 consecutive meningioma cases (N = 310 females; mean age 57.3 years) to examine concordance between frozen section evaluation of meningioma subtype and grade as compared with the final diagnosis subtype and grade. A discrepancy between frozen section diagnosis and final diagnosis was observed in 114 (26.9%) of cases. Of the WHO grade I subtypes, the most common discrepancy involved transitional meningiomas (N = 31) which were most commonly diagnosed at frozen section as either fibrous (N = 18) or meningothelial (N = 13) meningiomas. None of the grade I tumors were diagnosed as higher grade lesions. Of the higher grade meningiomas (WHO grade II and III) (N = 145) reviewed, concordance between tumor type and grade was seen in only 26.2% of cases; most commonly, 73/98 atypical meningiomas were under-graded as some subtype of WHO grade I meningioma (71/73 cases). In conclusion, discrepancies at frozen section with respect to accurately identifying higher grade meningiomas and higher grade meningioma subtypes are common and are generally due to tumor sampling and heterogeneity.



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Cutaneous infiltration of plasmacytoid dendritic cells and t regulatory cells in skin lesions of polymorphic light eruption

Abstract

Background

Polymorphic light eruption (PLE) is the most common autoimmune photodermatosis. Plasmacytoid dendritic cells (PDCs) are important mediators of innate anti-microbial immunity involved in the pathogenesis of many inflammatory skin diseases. In addition to PDCs, regulatory T cells (Tregs) are involved in controlling inflammation and adaptative immunity in skin by their immunosoppressive capacity.

Objective

The aim of the present study was to investigate the presence of PDCs and Tregs in photoexposed skin from PLE compared to healthy skin.

Methods

Patients with PLE diagnosis and healthy controls were recruited and underwent a photoprovocative test. A 4- mm punch biopsy was taken from the site of positive photoprovocation test reaction and immunohistochemistry for BDCA2 as marker for PDCs, CD4 and FOXP3 as markers for Tregs was performed. Double immunostain for FOXP3 and CD4 was performed as well.

Absolute counts for CD4, BDCA2 and FOXP3 were performed in at least 5 High Power Fields (HPF). Percentage of CD4, BDCA2 and CD4FOXP3 positive cells over the total inflammatory infiltrate was assessed for each case.

Results

We enrolled 23 patients and controls. BDCA2+ cells were present in 91.3% of PLE skin samples, and 100% of healthy volunteer. Both in PLE patients and healthy controls, PDCs distribution was mainly dermic (p<0.05).

Compared to healthy controls, both epidermic and dermic BDCA2+ cells count was significantly higher in PLE patients (p<0.05).

Both in PLE patients and healthy controls, Tregs distribution was mainly dermic (p<0.05).

The presence of both CD4+ cells and FOXP3+ cells was significantly higher in the dermis of PLE patients compared to controls (p<0.05). Relative percentages of cellular infiltrations confirmed these results.

Conclusions

D-PDCS and Tregs may play a significant role in the development of PLE and dermal distribution of PDCs in PLE skin biopsies seems to confirm a possible overlap with Cutaneous Lupus Erythematosus (CLE).

This article is protected by copyright. All rights reserved.

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Focal facial hyperhidrosis associated with internal carotid artery dissection successfully treated with botulinum toxin A

Abstract

Hyperhidrosis affects up to 3% of the population⁽¹⁾. Secondary hyperhidrosis may be associated with infections, malignancies, endocrine or neurological diseases⁽²⁾. We report the first case of localized hyperhidrosis associated to Pourfour du Petit syndrome secondary to internal carotid artery dissection successfully and safely treated with botulinum toxin.

This article is protected by copyright. All rights reserved.

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The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: Analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study)

Abstract

Background

Psychological aspect and quality of life should be considered in treating patients with psoriasis.

Objective

We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis.

Methods

The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1,260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the psoriatic arthritis (PsA) screening and evaluation (PASE), dermatology life quality index (DLQI), MOS 36-item short-form health survey (SF-36), work productivity and activity impairment questionnaire psoriasis (WPAI: PSO), and medication satisfaction questionnaire (MSQ).

Results

Patients with a DLQI score>5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA), and had higher PASE scores than patients with DLQI≤5 (n = 266). The group of patients with exposed lesions (n=871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n=389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment, and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental).

Conclusion

The presence of exposed lesions has a negative impact on quality of life, mental health, and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

This article is protected by copyright. All rights reserved.

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Dermoscopic Features of Tungiasis

Abstract

Tungiasis is a parasitic infection caused by the sand flea Tunga penetrans. Tungiasis is prevalent in rural Central and South America, the Caribbean and sub-Saharan Africa.¹ In some endemic areas, the overall infestation prevalence exceeds 50 percent, and it remains an important public health problem for poor communities.^1,2 In some cases, the eruptions can mimic viral warts, furuncles, abscesses and paronychia.¹ Dermoscopy is reported to be a useful tool for differentiating between these and tungiasis lesions.^3,4 Moreover, the majority of cases have multiple lesions, with the ectoparasites causing more than 50 lesions in a single individual in some cases,⁵ and dermoscopy can help find the lesions. Despite the clinical utility of dermoscopy, no reports have assessed the significance of each dermoscopic finding in tungiasis. Here we report a case of tungiasis and we review the dermoscopic findings of 11 lesions of the patient to reveal the characteristic findings.

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Psoriatic arthritis screening by the dermatologist: development and first validation of the “PURE-4 scale”

Abstract

Background

Dermatologists are recommended to ask psoriasis patients about musculoskeletal complaints to allow early detection and treatment of psoriatic arthritis (PsA). Screening tools have been developed to help identifying patients warranting further rheumatologic assessment, but evidence suggests room for improvement in their diagnostic value and ease of use for outpatient practice.

Objective

To develop and internally validate a brief tool for dermatologists to screen patients to refer to a rheumatologist for PsA diagnosis.

Methods

After literature review, 23 items were selected, covering pain at various locations and inflammatory signs of PsA. The validation study was conducted in medically diagnosed psoriasis patients consecutively recruited between 2012-2014 (Saint Joseph Hospital, Paris, France). Patients were enrolled by a dermatologist who helped to complete the questionnaire. Diagnosis of PsA was established by a rheumatologist based on CASPAR criteria. Multivariate logistic regression models were performed to build the scale, assessing discrimination through sensitivity, specificity and area under the ROC curve (AUC). Final model was internally validated using bootstrapping techniques.

Results

168 patients were recruited, of whom 9 were excluded for known PsA and 21 did not attend the rheumatologist consultation. Out of 137 included patients (median age 43 years, 59.6% men), 21 (15.3%) had a PsA diagnosis. Final regression model retained 4 independent items, including evocative signs of dactylitis, inflammatory heel pain, bilateral buttock pain and peripheral joint pain with swelling in patients aged<50. A total score (the PURE-4) was computed (0-4 points) that demonstrated excellent discriminative power (AUC=87.6%; Sensitivity=85.7% and Specificity=83.6% at the threshold of ≥1/4 points), with no evidence for over-optimism in bootstrapped internal validation.

Conclusion

These findings demonstrate the good diagnostic properties of a new screening scale using only 4 easy-to-collect items. If confirmed in other populations, it may prove useful in outpatient dermatology clinics for triage of psoriasis patients requiring further assessment by the rheumatologist.

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Patients affected by Dent disease 2 could be predisposed to hidradenitis suppurativa

Abstract

Dent disease 2 (DD2) is a rare X-Linked disorder characterized by proximal tubule dysfunction. It is considered as mild variant of Lowe Syndrome (LS) and both conditions are secondary to OCRL1 gene mutations.¹ Mutations in this gene drastically reduce (<10%) inositol polyphosphate 5-phosphatase (OCRL1) activity.¹

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Rapid Improvement of Psoriasis in a Patient with Lung Cancer after Treatment with Erlotinib

Abstract

We report the case of a 48-year-old woman with a rapid improvement of her psoriasis after treatment with erlotinib.A metastasised non-small cell lung cancer (NSCLC) was diagnosed and the psoriasis treatment with ustekinumab was stopped which caused a flare up of her psoriasis.

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In situ monitoring of PTHLH secretion in neuroblastoma cells cultured onto nanoporous membranes

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Alfredo de la Escosura-Muñiz, Marisol Espinoza-Castañeda, Alejandro Chamorro-García, Carlos J. Rodríguez-Hernández, Carmen de Torres, Arben Merkoçi
In this work, we propose for the first time the use of anodic aluminum oxide (AAO) nanoporous membranes for in situ monitoring of parathyroid hormone-like hormone (PTHLH) secretion in cultured human cells. The biosensing system is based on the nanochannels blockage upon immunocomplex formation, which is electrically monitored through the voltammetric oxidation of Prussian blue nanoparticles (PBNPs). Models evaluated include a neuroblastoma cell line (SK-N-AS) and immortalized keratinocytes (HaCaT) as a control of high PTHLH production. The effect of total number of seeded cells and incubation time on the secreted PTHLH levels is assessed, finding that secreted PTHLH levels range from approximately 60 to 400 ng/mL. Moreover, our methodology is also applied to analyse PTHLH production following PTHLH gene knockdown upon transient cell transfection with a specific silencing RNA (siRNA). Given that inhibition of PTHLH secretion reduces cell proliferation, survival and invasiveness in a number of tumors, our system provides a powerful tool for the preclinical evaluation of therapies that regulate PTHLH production. This nanoporous membrane – based sensing technology might be useful to monitor the active secretion of other proteins as well, thus contributing to characterize their regulation and function.

Graphical abstract

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Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes

Abstract

Objective

Previous studies have shown that enolase-1 (ENO1) in the stratum corneum (SC) is more highly expressed in patients with atopic dermatitis (AD) than in healthy individuals, suggesting that it is a novel biomarker for evaluating skin condition in patients with AD. However, the mechanism underlying high ENO1 expression in the SC and its pathological relevance in AD are unclear. In this study, the relationship between ENO1 expression and keratinization of epidermis was investigated and the role of high ENO1 expression in keratinocytes was characterized.

Methods

ENO1 expression and morphological characteristics were examined in SC from the cheeks of 24 patients with AD. Additionally, the localization of ENO1 in the excised human epidermis was observed. Moreover, to analyze the role of ENO1 in cellular barrier function, tight junction proteins (TJs) and trans-epithelial electrical resistance (TEER) in keratinocytes with ENO1 overexpression were evaluated. Furthermore, the localization of ENO1 and plasminogen in keratinocytes was evaluated by immunostaining, and the cellular barrier function in keratinocytes was examined after treatment with tranexamic acid (TXA).

Results

ENO1 expression was substantially correlated with the rate of nucleated corneocytes in AD. In addition, ENO1 localized in the basal to spinous layers, but was its expression dramatically decreased in healthy human SC. ENO1 overexpression in human epidermal keratinocytes reduced the expression of TJs (claudin-4, E-cadherin, tricellulin, and occludin) and TEER, and treatment with anti-ENO1 IgG reversed these effects. ENO1 co-localized with plasminogen in keratinocytes. Treatment with TXA rescued the ENO1-induced reductions in TJ and TEER expression.

Conclusion

We found a substantial correlation between ENO1 expression and the rate of nucleated corneocytes in AD and decreased ENO1 expression with nuclear disappearance. These results suggest that high ENO1 expression in the SC of AD is caused by deficient keratinization, which is an AD characteristic. Moreover, ENO1 overexpression in keratinocytes promoted dysfunction of TJ dynamics, leading to reduced integrity of the cellular barrier, and these effects might be mediated by plasmin activity. We propose that ENO1 is a useful indicator of parakeratosis and might have a potential role in cellular TJ barrier function in the epidermis.

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Breaking paradigms in severe epistaxis: the importance of looking for the S-point.

Breaking paradigms in severe epistaxis: the importance of looking for the S-point.

Braz J Otorhinolaryngol. 2018 Jan 20;:

Authors: Kosugi EM, Balsalobre L, Mangussi Gomes J, Tepedino MS, San da Silva DM, Cabernite EM, Hermann D, Stamm AC

Abstract
INTRODUCTION: Since the introduction of nasal endoscopy into the field of Otorhinolaryngology, the treatment paradigm for cases of severe epistaxis has shifted toward early and precise identification of the bleeding site. Although severe epistaxis is usually considered to arise from posterior bleeding, an arterial vascular pedicle in the superior portion of the nasal septum, around the axilla projection of the middle turbinate, posterior to the septal body, frequently has been observed. That vascular pedicle was named the S-point.
OBJECTIVE: The aim of this study was to describe the S-point and report cases of severe epistaxis originating from it.
METHODS: A retrospective case series study was conducted. Nine patients with spontaneous severe epistaxis, where the S-point was identified as the source of bleeding, were treated between March 2016 and March 2017.
RESULTS: Male predominance (77.8%) with age average of 59.3 years old were reported. Most cases presented comorbidities (88.9%) and were not taking acetylsalicylic acid (66.7%). A predominance of left sided involvement (55.6%) and anteroposterior bleeding being the principal initial presentation (77.8%) was seen. Six patients (66.7%) presented with hemoglobin levels below 10g/dL, and four (44.4%) required blood transfusion. Cauterization of S-point was performed in all patients, with complete resolution of bleeding. No patient experienced recurrence of severe epistaxis.
CONCLUSION: The S-point, a novel source of spontaneous severe epistaxis, is reported, and its cauterization was effective and safe. Otolaryngologists must actively seek this site of bleeding in cases of severe epistaxis.

PMID: 29426784 [PubMed - as supplied by publisher]

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Cholesterol and vitamin E-conjugated PEGylated polymeric micelles for efficient delivery and enhanced anticancer activity of curcumin: evaluation in 2D monolayers and 3D spheroids.

Cholesterol and vitamin E-conjugated PEGylated polymeric micelles for efficient delivery and enhanced anticancer activity of curcumin: evaluation in 2D monolayers and 3D spheroids.

Artif Cells Nanomed Biotechnol. 2018 Feb 09;:1-14

Authors: Muddineti OS, Vanaparthi A, Rompicharla SVK, Kumari P, Ghosh B, Biswas S

Abstract
A newly synthesized PEGylated cholesterol/α-tocopheryl succinate (α-TOS) linked polymer (CV) was self-assembled and loaded with curcumin to form a micellar system (C-CVM). The tri-functionalized amphiphilic polymer was constituted of hydrophobic cholesterol and α-TOS connected to hydrophilic PEG via a lysine linker. The synthesized polymer and the micelles were characterized by 1H NMR, DLS, zeta potentiometer, TEM, CMC determination and hemolysis studies. CVM displayed low CMC value of 15 µM with extent of hemolysis as less than 4%. The stable C-CVM with optimum % drug loading (14.2 ± 0.24) displayed Z average of 175.8 ± 0.68 nm with PDI (0.248 ± 0.075) and released curcumin in sustained manner in the in vitro drug release study. C-CVM demonstrated dose-dependent cellular uptake and cytotoxicity in murine melanoma, B16F10 and human breast cancer, MDA-MB-231 cell lines. CV exhibited marked reversal of drug resistance as indicated by significantly higher retention of P-glycoprotein substrate, rhodamine-123 in the resistant B16F10 cell line compared to standard P-glycoprotein inhibitor, verapamil. C-CVM demonstrated significantly higher spheroidal growth inhibition compared to C-PPM. The results provide strong evidence for CVM as promising drug delivery system and confirm the potential of C-CVM as chemotherapy in cancer.

PMID: 29426248 [PubMed - as supplied by publisher]

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Albumin coated cadmium nanoparticles as chemotherapeutic agent against MDA-MB 231 human breast cancer cell line.

Albumin coated cadmium nanoparticles as chemotherapeutic agent against MDA-MB 231 human breast cancer cell line.

Artif Cells Nanomed Biotechnol. 2018 Feb 09;:1-11

Authors: Azizi M, Ghourchian H, Yazdian F, Alizadehzeinabad H

Abstract
With the aim of dedicating toxicity of cadmium nanoparticles (CdNPs) against invasive breast cancer, with minimum damage to surrounding healthy cells, CdNPs were coated with albumin nanocarrier by nanoprecipitation method and named CdNPs@BSA. The characterization was done by TEM image, DLS and UV-Vis, fluorescence, circular dichroism spectroscopy. The cytotoxic efficacy of the CdNPs@BSA against human breast cancer cells (MDA-MB 231 cells) was examined by MTT assay. Apoptosis, as the mechanism of cell death, was verified by inverted microscopy, fluorescent microscopy, gel electrophoresis and flow cytometry. The role of ROS generation in apoptosis was also studied. It was found that the resulted CdNPs@BSA (diameter of 88 nm and zeta potential of about -18.85 mV) was suitable for penetration in tumour micro vessels. In the form of CdNPs@BSA, the 77% of the secondary structure and almost all of the tertiary structure remain intact. Comparing to CdNPs, CdNPs@BSA could significantly suppress the MDA-MB 231 while they were less toxic on WBCs. Therefore, they could be a brilliant candidate to be used as a chemotherapeutic agent against invasive breast cancer cells.

PMID: 29426245 [PubMed - as supplied by publisher]

http://ift.tt/2EBrTuR

Ideal Characteristics of a Laser-Protected Endotracheal Tube: ABEA and AHNS Member Survey and Biomechanical Testing.

Ideal Characteristics of a Laser-Protected Endotracheal Tube: ABEA and AHNS Member Survey and Biomechanical Testing.

Ann Otol Rhinol Laryngol. 2018 Feb 01;:3489418757549

Authors: Friedman AD, Gerber ME, Bhayani MK, Kuchta K, Kumar K, Ma A, Ren Y, Zhang LQ

Abstract
OBJECTIVES: To determine the characteristics of laser-protected endotracheal tubes (LPETs) valued by otolaryngologists performing transoral laser surgery in the head and neck and to measure LPET stiffness.
METHODS: An online questionnaire was completed by American Broncho-Esophagological Association (ABEA) and American Head and Neck Society (AHNS) members. LPET distal end compliance was measured in a biomechanics laboratory.
RESULTS: A total of 228 out of 2109 combined ABEA and AHNS members completed the survey. The following LPET characteristics, which were properties of the Medtronic Laser-Shield II tube (MLST), were highly valued: softness and flexibility, surface smoothness, and a tight-to-shaft balloon (all P < .01). Prior to industry-driven discontinuation of the MLST, 52% of surgeons (78% of fellowship-trained laryngologists [FTLs]) reported using it; afterward, 58% reported using the stainless steel, Mallinckrodt Laser-Flex tube (MLFT). Forty-six percent of all respondents (69% of FTLs) did not consider cost being a factor in LPET choice. Biomechanical testing revealed the distal end of the MLST to be 3.45 times more compliant than the MLFT ( P < .01).
CONCLUSION: Members of the ABEA and AHNS, particularly FTLs, highly value distinguishing properties of the now discontinued MLST. Manufacturers should consider this in the design of new LPETs.

PMID: 29426244 [PubMed - as supplied by publisher]

http://ift.tt/2G4hQv6

External Auditory Canal Dimensions, Age, and Cerumen Retention or Impaction in Persons With Down Syndrome.

External Auditory Canal Dimensions, Age, and Cerumen Retention or Impaction in Persons With Down Syndrome.

Ann Otol Rhinol Laryngol. 2018 Feb 01;:3489418756678

Authors: Dy AES, Lapeña JFF

Abstract
OBJECTIVE: To investigate associations between age, external auditory canal (EAC) dimensions, and cerumen retention/impaction among persons with Down syndrome (DS).
METHODS: This cross-sectional study evaluated EAC dimensions, cerumen retention/impaction, and middle ear status with pneumatoscopy after extraction in 130 persons with DS. Descriptive and inferential statistics correlated age, presence of impacted/retained cerumen, and EAC diameter.
RESULTS: Of 260 ears in 67 males and 63 females with average age of 9.48 years, 72.3% (188) had EAC of ≤4 mm. Those ≤1 year were 4.97 times more likely to have cerumen problems than those >1 year (95% CI, 1.45-17.02, P = .011). The odds of having cerumen problems with an EAC diameter of ≤4 mm were 3.31 times higher than with a diameter of 5 mm (95% CI, 1.46-7.50, P = .004), and odds of having cerumen impaction were as much as 6.19 times higher (95% CI, 2.38-16.08, P < .001). Male gender and low-lying external ear were also associated with increased odds of cerumen problems.
CONCLUSION: There is a high prevalence of cerumen retention/impaction in persons with DS compared to the general Philippine population and a higher prevalence rate for EAC stenosis than elsewhere. A canal diameter of 4 mm and below and age 1 year or less are associated with a significantly higher likelihood of cerumen retention/impaction.

PMID: 29426243 [PubMed - as supplied by publisher]

http://ift.tt/2nQQ3HY

Martin Vahlensieck, Maximilian Reiser: MRI of the musculoskeletal system : Thieme, Stuttgart, New York, Delhi, Rio de Janeiro, 2018, 677 p., format 23.5 × 31.5 cm, 2062 illustrations, ISBN 978-3-13-1165725, eISBN 978-3-13-1607928.

Martin Vahlensieck, Maximilian Reiser: MRI of the musculoskeletal system : Thieme, Stuttgart, New York, Delhi, Rio de Janeiro, 2018, 677 p., format 23.5 × 31.5 cm, 2062 illustrations, ISBN 978-3-13-1165725, eISBN 978-3-13-1607928.

Surg Radiol Anat. 2018 Feb 09;:

Authors: Grignon B

PMID: 29427175 [PubMed - as supplied by publisher]

http://ift.tt/2BkVkz8

Intralesional cryotherapy versus excision with corticosteroid injections or brachytherapy for keloid treatment: Randomised controlled trials.

Intralesional cryotherapy versus excision with corticosteroid injections or brachytherapy for keloid treatment: Randomised controlled trials.

J Plast Reconstr Aesthet Surg. 2018 Feb 06;:

Authors: Bijlard E, Timman R, Verduijn GM, Niessen FB, Hovius SER, Mureau MAM

Abstract
BACKGROUND: Keloids are a burden for patients due to physical, aesthetic and social consequences. Treatment remains a challenge due to therapy resistance and high recurrence rates. The main goals of treatment are to improve scar appearance and symptoms and patients' quality of life (QoL).
METHODS: Two multicentre, randomised controlled open trials that compared 1) intralesional cryotherapy with excision and corticosteroid injections for primary keloids, and 2) intralesional cryotherapy with excision and brachytherapy for therapy resistant keloids. Primary outcome was scar appearance assessed with the Patient and Observer Scar Assessment Scale. Secondary outcomes were patient reported QoL (Skindex-29, SF-36, EQ-5D-5L), recurrence rates and scar volume reduction. For analysis, a linear mixed model was used. Power analysis indicated 33 patients in each group were needed.
RESULTS: The trial was prematurely terminated after inclusion of 26 patients due to unexpectedly inferior outcomes after intralesional cryotherapy. For primary keloids no convincing difference between treatments was found, but surgery improved scar appearance while cryotherapy did not. For resistant keloids, excision followed by brachytherapy improved scar appearance (POSAS) and scar symptoms (itch and pain) significantly (p < 0.001, p < 0.001 and p = 0.006 respectively) while cryotherapy did not. Neither of the treatments caused indisputable improvements in QoL.
CONCLUSIONS: Intralesional cryotherapy is inferior to keloid excision followed by brachytherapy for resistant keloids. In primary keloids, intralesional cryotherapy reduced keloid volume and, therefore, may be used in these patients and specific cases. Primary keloid group size was too small to draw valid conclusions, further research on the efficacy of intralesional cryotherapy for primary keloids is warranted.

PMID: 29426811 [PubMed - as supplied by publisher]

http://ift.tt/2nSm5Dz