Head and Neck Diseases by Alexandros G.Sfakianakis: 07/16/17

Κυριακή 16 Ιουλίου 2017

Moving Beyond the Audiogram Towards a Patient-Centered, Interactive First Fit

This article describes the development, implementation and verification of the Hearing Profile in Connexx hearing aid fitting software that is based on objective and subjective hearing related factors in addition to the audiogram.

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Posterior cordotomy in bilateral vocal cord paralysis using monopolar microelectrodes and radiofrequency in 18 patients

Abstract

Posterior cordotomy is an option in the surgical treatment of bilateral vocal cord paralysis in adduction.

We present results obtained in 18 patients with bilateral vocal cord paralysis in adduction treated using microelectrodes terminal with tips in several angles, and a radiofrequency generator from 2008 to 2013.

The functional outcome was evaluated using postoperative spirometry, the decannulation time, and swallowing.

All patients except one were successfully decannulated and showed an increase in mid-inspiratory flow rates.

The angled shape of the ME tips permits a very good resection for cordotomy; ME and radiofrequency are an excellent alternative to CO2 laser.

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Extranasopharyngeal Angiofibroma Revisited

Abstract

Background

Angiofibromas in the head and neck region usually arise in the nasopharynx, but may also occur elsewhere. This study aims at evaluating the incidence and clinical features of extranasopharyngeal angiofibroma (ENA).

Material and Methods

Systematic review of the literature (Medline^® and Google^™) up to December 31^st, 2015.

Results

174 cases of ENA were retrieved from a total of 170 publications. In contrast to former publications and previous understanding, the nasal septum was by far the most common site of the disease. Four patients had a congenital lesion, the oldest patient was 87 years old (mean: 28.7 years; median: 23 years). Male gender was predominantly affected, but the sex ratio was more balanced (2.13:1) than in previous reports in the literature until 12/2015. The majority of patients presented with nasal obstruction, either in combination with epistaxis (25.8%) or other symptoms (12.6%). Symptoms had developed within 13.1 months on average (median: 4 months). Brisk bleeding resulted in 11 of 43 biopsy procedures. Surgical resection as first-line therapy was performed in 170 patients. A tumor regrowth within 12 months was registered in four patients.

Conclusion

The increasing awareness of ENA and the willingness to publish case reports -not only in Medline listed journals- resulted in a significant increase of published case reports lately. Although extremely rare, ENAs have to be taken into account in the differential diagnosis of unclear masses, particularly in adult patients presenting with a rapidly developing nasal obstruction resulting from a nasal septum tumor. Female gender or normal vascularity does not exclude the diagnosis. Transnasal resection is sufficient in most cases and recurrences are rare. Pathologists as well as clinicians should consider ENA in their differential diagnosis of any mass of the upper airway.

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The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma

Abstract

Objectives

Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between Human Papilloma Virus (HPV)-positive and negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR.

Methods

88 surgically treated patients were included in this retrospective chart review. HPV-positive and negative OPSCC were evaluated for prediction of outcome by LNR separately. The endpoints were five-year overall survival (OS) and recurrence free survival (RFS).

Results

The OS of all patients was 60.1%. In univariate analysis LNR was a significant predictor of overall survival rate (p=0.008) in OPSCC independently of the HPV status, as well as extracapsular spread. T-classification was only a significant predictor in the univariate analysis in HPV-positive OPSCC carcinoma. However, in the multivariate analysis LNR remained predictor of prognosis in all OPSCC and in HPV-negative OPSCC. In patients with HPV-positive OPSCC only T-classification reached significance to predict OS.

Conclusion

Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.

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Posterior cordotomy in bilateral vocal cord paralysis using monopolar microelectrodes and radiofrequency in 18 patients

Abstract

Posterior cordotomy is an option in the surgical treatment of bilateral vocal cord paralysis in adduction.

The functional outcome was evaluated using postoperative spirometry, the decannulation time, and swallowing.

All patients except one were successfully decannulated and showed an increase in mid-inspiratory flow rates.

The angled shape of the ME tips permits a very good resection for cordotomy; ME and radiofrequency are an excellent alternative to CO2 laser.

http://ift.tt/2tZNOWh

Extranasopharyngeal Angiofibroma Revisited

Abstract

Background

Material and Methods

Systematic review of the literature (Medline^® and Google^™) up to December 31^st, 2015.

Results

Conclusion

http://ift.tt/2twqJXP

The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma

Abstract

Objectives

Methods

Results

Conclusion

http://ift.tt/2u0hPoX

Involvement of adenosine triphosphate-binding cassette subfamily B member 1 in the augmentation of triacylglycerol excretion by Propionibacterium acnes in differentiated hamster sebocytes

Abstract

An onset of acne, a common inflammatory skin disease, is associated with excess sebum production and secretion in sebaceous glands. Because Propionibacterium acnes has been reported to augment intracellular sebum accumulation in sebaceous glands in hamsters, it remains unclear whether P. acnes influences sebum secretion from differentiated sebocytes. Both P. acnes culture media (Acnes73-CM) and formalin-killed P. acnes (F-Acnes73) dose-dependently increased the extracellular levels of triacylglycerol (TG), a major sebum component, and Rhodamine 123, a substrate of adenosine triphosphate-binding cassette (ABC) transporter, from differentiated hamster sebocytes (DHS). In addition, the gene expression of the ABC subfamily B member 1 (ABCB1) was dose-dependently augmented by adding Acnes73-CM and F-Acnes73 into DHS. Furthermore, the F-Acnes73-induced increase of TG excretion was suppressed by PSC833, a selective ABCB1 inhibitor. On the other hand, peptidoglycan (PGN), which is a Toll-like receptor 2 (TLR2) ligand in P. acnes, increased extracellular TG levels, transporter activity and ABCB1 mRNA expression in DHS. The PGN-augmented TG excretion was suppressed by PSC833. Thus, these results provide novel evidence that P. acnes facilitates sebum secretion due to the activation of ABCB1 concomitantly with the increased ABCB1 expression, which may result from the activation of the TLR2 pathway in DHS. Therefore, the ABCB1 inhibitor is likely to become a candidate as a possible therapeutic for the treatment of acne.

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Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo-controlled phase 3 trial

Abstract

Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16. Other end-points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI-75 (50% and 75% vs 0%, P < 0.01) and PGA response (59% and 75% vs 0%, P < 0.001). Substantial improvements in ISI, DLQI and NAPSI score were observed with both tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis.

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Novel COL5A1 mutation in a Chinese family with classic type of Ehlers–Danlos syndrome

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Secondary syphilis primarily presenting with multiple nodules on the scalp: Case report and published work review

Abstract

Syphilis, a sexually transmitted disease caused by Treponema pallidum, manifests with a broad spectrum of clinical presentations that usually involves skin. Nodular secondary syphilis occurs rarely, and mostly manifests as disseminated papulonodules or plaques over the trunk and limbs. We report an extremely rare case of nodular secondary syphilis that primarily presented with multiple nodules on the scalp, resembling Rosai–Dorfman disease or cutaneous malignant metastasis. Immunohistochemistry confirmed T. pallidum spirochetes microscopically.

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Increased endocan expression in lesional skin and decreased endocan expression in sera in atopic dermatitis

Abstract

Endocan is a novel human endothelial cell-specific molecule and is mainly expressed in endothelial cells in various tissues. Endocan has the capacity to inhibit leukocytes binding to the vascular endothelium. It also can promote the angiogenesis alongside vascular endothelial growth factor A. Through these functions, endocan has been implicated in the pathogenesis of various inflammatory diseases. To investigate the possible roles of endocan in atopic dermatitis (AD), we examined endocan expression in lesional skin and sera in patients with AD. Endocan mRNA and protein levels were increased in lesional skin of AD compared with healthy skin and endocan was expressed on epidermal keratinocytes and dermal endothelial cells. On the other hand, serum endocan levels in patients with AD were significantly lower than those in healthy controls. Our results suggest that elevated endocan expression in lesional skin may be associated with development of AD through angiogenesis and that decreased endocan expression in sera may be associated with increased leukocyte recruitment in AD.

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Case of inflammatory tinea corporis affecting the dorsal surface of the thumb in a nail salon technician

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European guideline for the management of pediculosis pubis

Abstract

Pediculosis pubis is caused by Phthirus pubis. The disease can be sexually transmitted. Patients main complain is of itch in the pubic area. The parasite can be spotted with the naked eye and blue macules can be observed in the pubic area. First line therapy consists of permethrin or pyrethrins with piperonyl butoxide. Second line therapy contains phenothrin, malathion and oral ivermectin. Partner management needs a look-back period of time of 3 months. Pubic lice incidence is increased in populations groups living in crowded spaces with scarce sanitary conditions as in time of war or disaster.

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Neural control of sweat secretion: a review

Abstract

Humans have 4 million exocrine sweat glands, which can be classified into two types: eccrine and apocrine glands. Sweat secretion is a constitutive feature, which is directly involved in thermoregulation and metabolism. Sweat secretion is regulated by both the central nervous system¹ and autonomic nervous system.² In peripheral areas, the ANS, especially the sympathetic nervous system (SNS), mediates the transmission of neurotransmitters to sweat glands. Two principal chemical mediators, acetylcholine and noradrenaline (NA)/adrenaline (ADR), are released by the SNS, which stimulate sweat secretion. In the CNS, the thermoregulatory center in the hypothalamus responds to the elevated body temperature by increasing sweating, whereas emotional stresses stimulate the limbic system to induce sweating. The ANS mediates sweating that is due to stimulation of the thermoregulatory center and limbic system. In this review, we focus on the neural control of sweat secretion and the mechanisms by which chemical mediators induce sweating. In addition, we will discuss the sweating disorders associated with neural anomaly as well as the treatments.

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The BRAF and NRAS mutation prevalence in dermoscopic subtypes of acquired naevi reveals constitutive MAPK pathway activation

Summary

Background

Acquired naevi can have unique dermoscopic patterns that correspond to distinct microanatomical growth patterns. Previous studies on acquired naevi stratified according to dermoscopic pattern, focused on the frequency of somatic BRAF mutations, whereas NRAS mutations remained to be elucidated.

Objectives

To investigate the BRAF and NRAS mutation prevalence and activation of the MAPK pathway in distinct dermoscopic subtypes of acquired naevi.

Methods

Common mutations present in BRAF and NRAS were assessed in 40 globular, reticular, and peripheral rim of globules (PG) subtypes of acquired naevi from 27 participants (19 male, 8 female; mean age 46.7 years) selected from 1261 eligible volunteers. Mutations were determined using the highly sensitive and quantitative QX200 droplet digital^™ PCR (ddPCR) system.

Results

The BRAFV600E (c.1799T>A or c.1799_1800delTGinsA) and BRAFV600K mutations were detected in 85% (n=34/40) of naevi. All BRAF wild-type naevi (15%; n=6/40) harboured an NRAS codon 12/13 or 61 mutation. BRAF mutations were present in 92% (n=12/13) of globular and 100% (n=12/12) of PG naevi, whereas reticular naevi were 67% (n=10/15) BRAF and 33% (n=5/15) NRAS mutant (p=0.037).

Conclusions

We discovered that 100% of the assessed acquired naevi had either a BRAF or NRAS mutation. Using sensitive techniques capable of single-cell mutation detection, it is likely that all acquired naevi will be mutated for BRAF or NRAS. Since both of these mutations are prevalent in distinct dermoscopic naevus subsets, our study supports the role of the MAPK pathway in the development of benign melanocytic proliferations, indicating that additional genomic events besides somatic mutations in BRAF or NRAS are required for melanoma development.

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Neural control of sweat secretion: a review

Abstract

http://ift.tt/2uztnB8

The BRAF and NRAS mutation prevalence in dermoscopic subtypes of acquired naevi reveals constitutive MAPK pathway activation

Summary

Background

Objectives

To investigate the BRAF and NRAS mutation prevalence and activation of the MAPK pathway in distinct dermoscopic subtypes of acquired naevi.

Methods

Results

Conclusions

http://ift.tt/2v8eUcn

An uncommon cause of warm foot

Description

A 66-year-old man presented with swelling and redness of right foot of 1 month duration. He was a known diabetic for 20 years; glycaemic control was suboptimal. There was no history of trauma, fever, ulcer or deformity. He had numbness of both feet and was earlier documented to have mild non-proliferative diabetic retinopathy. On examination, he was not feverish with erythema, swelling (figure 1), local rise of temperature of the right foot and a difference of 2°C between both feet and no tenderness on palpation. There was loss of protective sensations with absent ankle jerks with bounding pulses in both feet. Systemic examination was unremarkable. His blood investigations revealed haemoglobin of 12 g/dL (N 12–15), total white cell count of 9.8x10⁹ /L/cmm (N 4000–11000), erythrocyte sedimentation rate of 48 mm/hour and haemoglobin A1c of 8.1% (n<5.7). Based on history and clinical findings and absent elevation of acute inflammatory markers, a diagnosis of acute...

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IgG4-related disease: long-term natural history and management of a relapsing multisystem disease entity

Although awareness of IgG4-related disease has grown over the past decade, with earlier diagnosis and treatment, understanding of its natural history over the long term and the optimal management remains unclear. We report the case of a 48-year-old man who presented with a pancreatic pseudotumour causing bile duct obstruction with coexisting autoimmune hepatitis and multisystem involvement. His symptoms settled on steroids and maintenance with azathioprine was commenced, however periodic relapses occurred involving multiple organs. A timeline-relating IgG4 levels, clinical features and immunosuppressive therapy are presented. The protean and relapsing–remitting nature of this condition is emphasised, and a brief review of long-term therapeutic options is provided.

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Solitary fibrous tumour: a rare tumour of the pleural cavity

Solitary fibrous tumours are a rare group of tumours that originate from connective tissues such as the pleura and mediastinum. When growing within the thoracic cavity these tumours exert pressure on vital organs and large vessels. We have successfully operated on two patients with large solitary fibrous tumours and managed the pathophysiological changes manifested as superior vena cava syndrome resulting from these tumours.

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Necrotising enterocolitis after supraventricular tachycardia: an unusual precursor to a common problem

Supraventricular tachycardia (SVT) is the most common neonatal arrhythmia. Necrotising enterocolitis (NEC) is a disease with multifactorial aetiology, most common in preterm infants. There are three previous case reports in the literature of NEC following neonatal SVT. We present two cases of late preterm infants with NEC, characterised by pneumatosis on abdominal X-ray and ultrasound, following recurrent SVT without haemodynamic instability. The infants were successfully treated with antibiotic therapy and bowel rest.

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The Duari hernia and recognition of the femoral vein compression sign

Femoral hernias can be difficult to diagnose and are at high risk of strangulation. This report is of a rare case of an irreducible femoral hernia containing caecum and appendix presenting as an emergency. To the authors' knowledge, there have only been three cases reported, the first described by Duari. This case was incorrectly diagnosed preoperatively as an inguinal hernia, so the CT diagnosis of femoral hernias is reviewed, in particular demonstrating the radiological use of the femoral vein compression sign.

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Syndromic congenital diarrhoea: new SPINT2 mutation identified in the UAE

We are reporting a new mutation in the SPINT2 gene (c.443G>A (p. Arg148His)) that explains the association of choanal atresia with congenital sodium diarrhoea (CSD) in an Emirati family in the Middle East. To our knowledge, this mutation is neither listed in a mutation database nor described in the literature. Similar to other patients with CSD associated with SPINT2, this child remains dependent on parenteral nutrition for fluids and nutritional support resulting in failure to thrive. The determination of the molecular basis of syndromic CSD will facilitate prenatal and postnatal diagnosis of patients and will contribute to counselling of affected families, especially in areas like the UAE where consanguineous marriages are not uncommon.

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Preparing pathology for the molecular era

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Alpha subunit in clinically non-functioning pituitary adenomas: an immunohistochemical study

Publication date: Available online 16 July 2017
Source:Pathology - Research and Practice
Author(s): Michael Solarski, Fabio Rotondo, Luis V. Syro, Michael D. Cusimano, Kalman Kovacs
Pituitary adenomas may be classified as either functioning or non-functioning, depending on whether excess hormone secretion can be clinically identified. Of the six hormones produced in the anterior pituitary, TSH, FSH and LH are known as glycoproteins and contain two subunits (α and β). While α-subunit is identical within all of them, each β-subunit is unique and biologically specific. Independently, the α- and β-subunits are inactive and only induce a hormonal response when they are non-covalently associated. Studies have shown that in certain cases, pituitary adenomas may abnormally secrete only α-subunit, detectable the serum or through immunohistochemical analysis. In the present study, we examined α-subunit immunoexpression in surgically removed non-functioning pituitary adenomas and analyzed its prognostic value. Results showed that expression of α-subunit in clinically non-functioning pituitary adenomas is not a rare occurrence. While there were no age/gender differences between tumors that expressed α-subunit and those that did not, α-subunit immunonegative adenomas presented with suprasellar extension more frequently and had an Ki67 proliferation more than 3%. The use of immunohistochemical techniques to determine the presence of α-subunit may provide information on tumor cell proliferation and biologic behavior. To fully understand the role of α-subunit in pituitary adenomas more work is needed.

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Letter to the editor: health professionals’ attitudes toward individuals with eating disorders: who do we think they are?

Abstract

Health professionals are not immune to stigmatizing attitudes and stereotypes found in society-at-large. Along with patients and their loved ones, treatment providers are important stakeholders – and gatekeepers – in the successful delivery of mental healthcare. Prevailing attitudes among professionals can facilitate timely recognition, enable access to care and uptake of evidence-based practices, or undermine help-seeking and therapeutic engagement. At an interactive activity at the 2016 Nordic Eating Disorders Society (NEDS) meeting, we asked health professionals to describe individuals with eating disorders. The most common descriptive term used was "anxiety" followed by "thin", "sad", "control", "female", and "suffering/pain". Further research on professionals' attitudes toward individuals with eating disorders is necessary to inform education, awareness, and advocacy efforts following the diagnostic revisions in the DSM-5.

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Twenty-five years of gene therapy for genetic diseases and leukemia: The road to marketing authorization of the first ex vivo gene therapies

Publication date: Available online 16 July 2017
Source:Journal of Autoimmunity
Author(s): Claudio Bordignon

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Diagnosing allergic sensitizations in the third millennium: why clinicians should know allergen molecule structures

Diagnostic tests to detect allergic sensitization were introduced at the end of the nineteenth century but only in the late 1990s did the advent of molecular allergology revolutionize the approach to the aller...

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Diagnosing allergic sensitizations in the third millennium: why clinicians should know allergen molecule structures

DNA binding and unwinding by Hel308 helicase requires dual functions of a winged helix domain.

Publication date: Available online 16 July 2017
Source:DNA Repair
Author(s): Sarah J. Northall, Ryan Buckley, Nathan Jones, J. Carlos Penedo, Panos Soultanas, Edward L. Bolt
Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in a "ratchet" for directional translocation. A winged helix domain (WHD) is also present, but its function is mysterious. We investigated the WHD in full-length Hel308, identifying that mutations in a solvent exposed α-helix resulted in reduced DNA binding and unwinding activities. When isolated from the rest of Hel308, the WHD protein alone bound to duplex DNA but not ssDNA, and DNA binding by WHD protein was abolished by the same mutations as were analyzed in full-length Hel308. Isolated WHD from a human Hel308 homologue (HelQ) also bound to duplex DNA. By disrupting the interface between the Hel308 WHD and a RecA-like domain, a topology typical of Ski2 helicases, we show that this is crucial for ATPase and helicase activities. The data suggest a model in which the WHD promotes activity of Hel308 directly, through binding to duplex DNA that is distinct from ssDNA binding by core helicase, and indirectly through interaction with the RecA-like domain. We propose how the WHD may contribute to ssDNA translocation, resulting in DNA helicase activity or in removal of other DNA bound proteins by "reeling" ssDNA.

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Planktonic Growth of Pseudomonas aeruginosa around a Dual-Species Biofilm Supports the Growth of Fusobacterium nucleatum within That Biofilm

Purpose. The goal of this study was to understand the potential interaction between Pseudomonas aeruginosa and Fusobacterium nucleatum within the middle ear. Methods. We examined the microbiota of ear fluid and tympanostomy tubes (TTs) obtained from patients with posttympanostomy tube otorrhea. We also examined biofilms formed by P. aeruginosa and F. nucleatum, singly or together, under aerobic or anaerobic conditions. Results. While the facultative anaerobe P. aeruginosa dominated the bacterial population within the ear fluid, strict anaerobes, including F. nucleatum, dominated bacterial populations within the TTs. F. nucleatum was able to grow under aerobic conditions only in the presence of P. aeruginosa, whose growth reduced the level of dissolved oxygen within the broth to nearly anoxic condition within 4 h after inoculation. The presence of P. aeruginosa allowed F. nucleatum to maintain its growth for 72 h within the dual-species biofilm but not within the planktonic growth. Visualization of the biofilms revealed coaggregation of P. aeruginosa and F. nucleatum. Conclusion. Extrapolation of these results suggests that, within the middle ear fluid, the growth of P. aeruginosa produces the anaerobic conditions required for the growth of F. nucleatum, both within effusion and within biofilms.

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Planktonic Growth of Pseudomonas aeruginosa around a Dual-Species Biofilm Supports the Growth of Fusobacterium nucleatum within That Biofilm

Spectral Doppler ultrasound of peripheral arteries: a pictorial review

Publication date: Available online 16 July 2017
Source:Clinical Imaging
Author(s): Zachary Nuffer, Andrey Rupasov, Neel Bekal, Jacqueline Murtha, Shweta Bhatt
This article reviews the pathophysiology and sonographic findings of peripheral arterial lesions, with emphasis on the spectral Doppler waveforms encountered in each. It discusses the characteristic features of the Doppler spectra in obstructive conditions, including thromboembolism, atherosclerotic disease, bypass graft occlusion, dissection, trauma, and compartment syndrome, as well as non-obstructive conditions, including hyperemia, pseudoaneurysm, and arteriovenous fistula. Familiarity with the commonly-encountered spectral waveforms in the setting of these lesions is necessary for timely and accurate diagnosis and treatment.

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Preoperative clinic: Non-essential cost or catalyst for process efficiency, safety and care outcomes?

As the inevitable consequences of healthcare reform legislations are hitting the bottom line of hospitals, perioperative communities are undergoing continued intense scrutiny for opportunities to improve efficiency, safety and patient centered care. In the current issue of JCA Epstein and colleagues [1] studied the effect of bypassing an anesthesiologist-directed preoperative evaluation clinic on first-case tardiness and turnover times. In their institution, efforts to reduce cost increasingly directed patients away from their anesthesiologist-directed preoperative clinic.

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Participation of Colon and Rectal Fellows in Robotic Rectal Cancer Surgery: Effect on Surgical Outcomes

Publication date: Available online 15 July 2017
Source:Journal of Surgical Education
Author(s): Danielle Collins, Nikolaos Machairas, Emilie Duchalais, Ron G. Landmann, Amit Merchea, Dorin T. Colibaseanu, Scott R. Kelley, Kellie L. Mathis, Eric J. Dozois, David W. Larson
ObjectivesTo determine whether involvement of colon and rectal fellows has an effect on short-term surgical and oncological outcomes in robotic rectal cancer surgery.Patients and MethodsFrom a dataset of 263 robotic-assisted rectal cancer operations, 114 case-matched patients over a 5-year period (January 2010-December 2015) were included in the study. Patients who underwent resection with and without fellow involvement were compared. Cases were matched according to age, body mass index, neoadjuvant therapy, and tumor location. Intraoperative, postoperative, and pathological outcomes were compared between the 2 groups.ResultsThere was no difference in tumor grade, type of surgical procedure, presence of an anastomosis, or diverting stoma between groups. In addition, there was no difference in the incidence of intraoperative or postoperative complications between the 2 groups. Estimated blood loss was higher in the fellow group compared to the consultant group (mean difference of 70mL, p = 0.007). For pathological outcomes, there was no difference in surrogate oncological quality indicators, specifically margin positivity and lymph node yield, between the 2 groups. Furthermore, fellow involvement did not adversely affect operative time.ConclusionThis study demonstrates that equivalent short-term surgical and oncological outcomes can be achieved with colorectal fellow participation in the field of robotic-assisted rectal cancer surgery.

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Toward Best Practices for Surgical Morbidity and Mortality Conferences: A Mixed Methods Study

Publication date: Available online 15 July 2017
Source:Journal of Surgical Education
Author(s): Marit S. de Vos, Perla J. Marang-van de Mheen, Ann D. Smith, Danny Mou, Edward E. Whang, Jaap F. Hamming
ObjectiveTo assess formats for surgical morbidity and mortality conferences (M&M) for strengths and challenges.DesignA mixed methods approach with local observations to assess key domains of M&M practice (i.e., goals, structure, and process/content) and surveys to assess participants' expectations and experiences.SettingSurgical departments of two teaching hospitals (Boston, USA and Leiden, Netherlands).ParticipantsParticipants of surgical M&M, including attending surgeons, residents, physician assistants, and medical students (total n = 135).ResultsSurgical M&M practices at both hospitals had education as its overarching goal, but varied in structure and process/content. Expectations were similar at both sites with ≥80% of participants (n = 90; 67% response) expecting M&M to be focused on education as well as quality improvement (QI), blame-free, mandatory for both residents and attendings, and to lead to changes in clinical practice. However, compared to expectations, significantly fewer participants at both sites experienced: a QI focus (both p < 0.001); mandatory faculty attendance (p = 0.004; p < 0.001) and changes to practice (both p < 0.001). In comparison, at the site where an active moderator and QI committee are present, respondents seemed more positive about experiencing a QI focus (73% vs 30%) and changes to practice (44% vs 16%).ConclusionDespite variation in M&M practice, the same (unmet) expectations existed at both hospitals, indicating that certain challenges may be more universal. M&M was reported to be well-focused on education, and certain aspects (e.g., active moderator and QI committee) seemed beneficial, but expectations were not met for the conference's focus and function for QI. Greater exchange of "best practices" for M&M may enhance the conference's value for improving surgical care.

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The terminal latency of the phrenic nerve correlates with respiratory symptoms in amyotrophic lateral sclerosis

Publication date: September 2017
Source:Clinical Neurophysiology, Volume 128, Issue 9
Author(s): Jin-Sung Park, Donghwi Park
ObjectiveThe aim of the study was to investigate the electrophysiological parameters in phrenic nerve conduction studies (NCS) that sensitively reflect latent respiratory insufficiency present in amyotrophic lateral sclerosis (ALS).MethodForty-nine patients with ALS were examined, and after exclusion, 21 patients with ALS and their phrenic NCS results were reviewed. The patients were divided into two groups according to their respiratory sub-score in the ALS functional rating scale - revised (Group A, sub-score 12vs. Group B, sub-score 11). We compared the parameters of phrenic NCS between the two groups.ResultsThere were no significant differences in the clinical characteristics between the two groups. Using a multivariate model, we found that the terminal latency of the phrenic nerve was the only parameter that was associated with early symptoms of respiratory insufficiency (p<0.05). The optimal cutoff value for the terminal latency of the phrenic nerve was 7.65ms (sensitivity 80%, specificity 68.2%).ConclusionThe significantly prolonged terminal latency of the phrenic nerve in our study may reflect a profound distal motor axonal dysfunction of the phrenic nerve in patients with ALS in the early stage of respiratory insufficiency that can be used as a sensitive electrophysiological marker reflecting respiratory symptoms in ALS.SignificanceThe terminal latency of the phrenic nerve is useful for early detection of respiratory insufficiency in patients with ALS.

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Using wheel availability to shape running behavior of the rat towards improved behavioral and neurobiological outcomes

Publication date: Available online 15 July 2017
Source:Journal of Neuroscience Methods
Author(s): Julia C. Basso, Joan I. Morrell
BackgroundThough voluntary wheel running (VWR) has been used extensively to induce changes in both behavior and biology, little attention has been given to the way in which different variables influence VWR. This lack of understanding has led to an inability to utilize this behavior to its full potential, possibly blunting its effects on the endpoints of interest.New MethodWe tested how running experience, sex, gonadal hormones, and wheel apparatus influence VWR in a range of wheel access "doses".ResultsVWR increases over several weeks, with females eventually running 1.5 times farther and faster than males. Limiting wheel access can be used as a tool to motivate subjects to run but restricts maximal running speeds attained by the rodents. Additionally, circulating gonadal hormones regulate wheel running behavior, but are not the sole basis of sex differences in running. Comparison with Existing Method(s): Limitations from previous studies include the predominate use of males, emphasis on distance run, variable amounts of wheel availability, variable light-dark cycles, and possible food and/or water deprivation. We designed a comprehensive set of experiments to address these inconsistencies, providing data regarding the "microfeatures" of running, including distance run, time spent running, running rate, bouting behavior, and daily running patterns.ConclusionsBy systematically altering wheel access, VWR behavior can be finely tuned – a feature that we hypothesize is due to its positive incentive salience. We demonstrate how to maximize VWR, which will allow investigators to optimize exercise-induced changes in their behavioral and/or biological endpoints of interest.

Graphical abstract

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Evolutionary basis of a new approach for the treatment of malignant brain tumors: From mice to humans

Publication date: Available online 15 July 2017
Source:Clinical Immunology
Author(s): Pedro R. Lowenstein, Maria G. Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14–20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials. Why the immune system fails to recognize the growing brain tumor is not completely understood. We believe that one reason for this failure is that the brain lacks cells that perform the role that dendritic cells serve in other organs. The lack of functional dendritic cells from the brain causes the brain to be deficient in priming systemic immune responses to glioma antigens. To overcome this drawback we reconstituted the brain immune system for it to initiate and prime anti-glioma immune responses from within the brain. To achieve brain immune reconstitution adenoviral vectors are injected into the resection cavity or remaining tumor. One adenoviral vector expresses the HSV-1 derived thymidine kinase which converts ganciclovir into phospho-ganciclovir which becomes cytotoxic to dividing cells. The second adenovirus expresses the cytokine fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L differentiates precursors into dendritic cells and acts as a chemokine for dendritic cells. This results in HSV-1/ganciclovir killing of tumor cells, and the release of tumor antigens, which are then taken up by dendritic cells recruited to the brain tumor microenvironment by Flt3L. Concomitant release of HMGB1, a TLR2 agonist that activates dendritic cells, stimulates dendritic cells loaded with glioma antigens to migrate to the cervical lymph nodes to prime a systemic CD8+ T cytotoxic killing of brain tumor cells. This induced immune response causes glioma-specific cytotoxicity, induces immunological memory, and does not cause brain toxicity or autoimmunity. A Phase I Clinical Trial, to test our hypothesis in human patients, was opened in December 2013 (see: NCT01811992, Combined Cytotoxic and Immune-Stimulatory Therapy for Glioma, at ClinicalTrials.gov). This trial is a first in person trial to test whether the re-engineering of the brain immune system can serve to treat malignant brain tumors. The long and winding road from the laboratory to the clinical trial follows below.

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Evolutionary basis of a new approach for the treatment of malignant brain tumors: From mice to humans

Pharmacokinetics of intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor [ 14 C]copanlisib (BAY 80-6946) in a mass balance study in healthy male volunteers

Abstract

Purpose

To determine the pharmacokinetics of radiolabeled copanlisib (BAY 80-6946) in healthy male volunteers and to investigate the disposition and biotransformation of copanlisib.

Methods

A single dose of 12 mg copanlisib containing 2.76 MBq [¹⁴C]copanlisib was administered as a 1-h intravenous infusion to 6 volunteers with subsequent sampling up to 34 days. Blood, plasma, urine and feces were collected to monitor total radioactivity, parent compound and metabolites.

Results

Copanlisib treatment was well tolerated. Copanlisib was rapidly distributed throughout the body with a volume distribution of 1870 L and an elimination half-life of 52.1-h (range 40.4–67.5-h). Copanlisib was the predominant component in human plasma (84% of total radioactivity AUC) and the morpholinone metabolite M1 was the only circulating metabolite (about 5%). Excretion of drug-derived radioactivity based on all 6 subjects was 86% of the dose within a collection interval of 20–34 days with 64% excreted into feces as major route of elimination and 22% into urine. Unchanged copanlisib was the main component excreted into urine (15% of dose) and feces (30% of dose). Excreted metabolites (41% of dose) of copanlisib resulted from oxidative biotransformation.

Conclusions

Copanlisib was eliminated predominantly in the feces compared to urine as well as by hepatic biotransformation, suggesting that the clearance of copanlisib would more likely be affected by hepatic impairment than by renal dysfunction. The dual mode of elimination via unchanged excretion of copanlisib and oxidative metabolism decreases the risk of clinically relevant PK-related drug–drug interactions.

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Methylation-associated silencing of SFRP1 gene in high-grade serous ovarian carcinomas

Publication date: Available online 15 July 2017
Source:Annals of Diagnostic Pathology
Author(s): Vedran Kardum, Valentina Karin, Mislav Glibo, Anita Skrtic, Tamara Nikuseva Martic, Nermina Ibisevic, Faruk Skenderi, Semir Vranic, Ljiljana Serman
Wnt is a highly conserved signaling pathway responsible for tissue regeneration, maintenance and differentiation of stem cells in adults. Its aberrant activation through reduced expression of Wnt signaling pathway inhibitors, such as proteins from the SFRP family, is commonly seen in many tumors. In the present study we explored SFRP1 protein expression using immunohistochemistry in 11 low-grade serous ovarian carcinomas (LGSC), 42 high-grade serous ovarian carcinomas (HGSC), and 5 normal ovarian tissues (controls). SFRP1 gene methylation was analyzed by methylation-specific PCR in 8 LGSCs, 13 HGSCs and control samples. SFRP1 gene was unmethylated and SFRP1 protein expression was strong in normal ovaries (n=5). Although SFRP1 gene was unmethylated in almost all of the LGSC cases (7/8, 88%), SFRP1 protein expression was significantly lower than in normal ovaries (p<0.05). Seven out of 13 HGSCs (54%) showed SFRP1 gene hypermethylation and protein expression level was also significantly lower than in normal ovaries (p<0.001). Our preliminary data show loss of SFRP1 protein expression caused by the SFRP1 promoter hypermethylation in a subset of HGSCs. SFRP1 protein expression was also lost in LGSCs but different regulatory mechanisms may be involved. Further studies should elucidate the clinical and therapeutic relevance of the observed molecular alterations.

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Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab.

Publication date: Available online 16 July 2017
Source:Journal of Dermatological Science
Author(s): Yasuhiro Fujisawa, Koji Yoshino, Atsushi Otsuka, Takeru Funakoshi, Taku Fujimura, Yuki Yamamoto, Hiroo Hata, Masahiko Gosho, Ryota Tanaka, Kei Yamaguchi, Yumi Nonomura, Ikuko Hirai, Sadanori Furudate, Hisako Okuhira, Keisuke Imafuku, Megumi Aoki, Shigeto Matsushita
BackgroundAlthough nivolumab significantly prolongs survival of metastatic melanoma, about 10% of patients experience severe, even fatal immune-related adverse events (irAEs). Biomarkers to predict irAEs are, therefore, of great interest.ObjectiveWe aimed to correlate changes in routine blood count parameters to the occurrence of serious irAEs (grade 3/4 [G3/4] or lung/gastrointestinal [lung/GI] irAEs) in patients with melanoma who were treated with nivolumab.MethodsWe retrospectively analyzed data from 101 patient with melanoma treated with nivolumab from 8 institutes in Japan. We used logistic regression analyses to investigate associations between severe irAEs and fluctuations in routine blood count parameters (total white blood cell [WBC] count, relative neutrophil, monocyte, lymphocyte, and eosinophil count) during the treatment. Receiver-operating characteristic curve was used to determine a cutoff value for the blood count parameters and area under the curve (AUC).ResultsUnivariate analysis revealed that G3/4 irAEs were associated with increased total WBC count (P=0.034, cutoff value=+27%, AUC=0.68, odds ratio [OR]=1.58) and decreased relative lymphocyte count (RLC, P=0.042, cutoff value=−23%, AUC=0.65, OR=1.65). However, multivariate analysis showed that the same factors, increased WBC count (P=0.014, cutoff value=+59.1%, AUC=0.79, OR=6.04) and decreased RLC (P=0.012, cutoff value=−32.3%, AUC=0.81, OR=5.01) were independent factors associated with lung/GI irAEs.ConclusionsOur results suggest that increased WBC count and decreased RLC are associated with G3/4 and lung/GI irAEs. Our analysis was based on the data point at which irAE occurrence was noticed and, therefore, these factors are not predictive, however, they could be a "signal" of severe irAE occurrence in patients with melanoma treated with nivolumab.

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Increased frequencies of basophils, type 2 innate lymphoid cells and Th2 cells in skin of patients with atopic dermatitis but not psoriasis

Publication date: Available online 15 July 2017
Source:Journal of Dermatological Science
Author(s): Shunya Mashiko, Heena Mehta, Robert Bissonnette, Marika Sarfati
BackgroundPathogenesis of atopic dermatitis (AD) involves interaction between type 2 cells that include basophils, mast cells, innate lymphoid type 2 cells (ILC2), and Th2 cells. Levels of IL-4 and IL-13 are elevated in AD patients.ObjectiveHere, we investigated the distribution of type 2 cells and the source of IL-4 and IL-13 in skin and blood of AD relative to psoriasis.MethodsLesional skin biopsies and blood were collected from patients. Skin cell suspensions were prepared by mild enzymatic digestion and mechanical dissociation. IL-4 and IL-13 expression was analyzed at single-cell level before or after stimulation using flow cytometry.ResultsFrequencies of basophils, ILC2 and Th2 but not mast cells were significantly elevated in skin, and not blood, of AD relative to psoriasis. IL-4 production by circulating basophils and Th2 cells, and IL-13 by ILCs and Th2 cells was similar in both diseases. In contrast, skin T cells expressed IL-4 and IL-13 prior to stimulation in AD when compared to psoriasis. Moreover, skin basophils, which were detected in AD only, expressed IL-4 following stimulation. Interestingly, basophils and ILC2 were positively correlated in skin whereas skin basophils were inversely correlated with blood ILC2.ConclusionsLesional AD skin harbors a distinctive innate and adaptive type 2 profile, which is characterized by basophils producing IL-4, Th2 cells expressing IL-4 or IL-13, and ILC2. This underlies the therapeutic efficacy of targeting IL-4 and IL-13 signaling pathways in AD.

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Epidemiology and comorbidities of patients with chronic urticaria in Taiwan‏: a nationwide population-based study

Publication date: Available online 15 July 2017
Source:Journal of Dermatological Science
Author(s): Chia-Yu Chu, Yung-Tsu Cho, Jhih-Hua Jiang, Eve I-Chun Lin, Chao-Hsiun Tang
BackgroundComprehensive data regarding the epidemiology of chronic urticaria (CU) in general populations are scant.ObjectivesTo investigate the prevalence, incidence, and comorbidities of CU in general population.MethodsThe data were sourced from the National Health Insurance Research Database (NHIRD) for 2009-2012. Patients who had a primary/secondary ICD-9-CM diagnosis code of 708.1, 708.8, or 708.9 during the year with at least two outpatient visits and an antihistamine prescription, were identified as the cases of CU for each year. The incidence, persistence and comorbidities of CU were examined.ResultsThe prevalence of CU ranged from 0.69% to 0.79% for each year from 2009-2012, and the incidence was around 0.50% per year from 2010-2012. Comparing to the Standard Population, the standardized prevalence ratios (SPRs) for the rheumatic diseases, thyroid disorders, inflammatory diseases, and psychiatric disorders among CU patients were 2.74, 1.81, 1.57 and 1.87, respectively.ConclusionThe prevalence of CU in Taiwan is about 0.69-0.79%. CU is associated with a significantly increased risk of psychiatric disorders, inflammatory diseases, thyroid disorders, and rheumatic diseases. Except for thyroid disorders, the prevalence of these comorbidities tends to increase the longer CU persists.

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Determination of chemical forms of 14C in liquid discharges from nuclear power plants

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): I. Svetlik, M. Fejgl, P.P. Povinec, T. Kořínková, L. Tomášková, J. Pospíchal, M. Kurfiřt, R. Striegler, M. Kaufmanová
Developments of radioanalytical methods for determination of radiocarbon in wastewaters from nuclear power plants (NPP) with pressurized light water reactors, which would distinguish between the dissolved organic and inorganic forms have been carried out. After preliminary tests, the method was used to process pilot samples from wastewater outlets from the Temelín and Dukovany NPPs (Czech Republic). The results of analysis of pilot water samples collected in 2015 indicate that the instantaneous ¹⁴C releases into the water streams would be about 7.10⁻⁵ (Temelín) and 4.10⁻⁶ (Dukovany) of the total quantity of the ¹⁴C liberated into the environment.

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Langerhans Cells – The Macrophage in Dendritic Cell Clothing

Publication date: Available online 15 July 2017
Source:Trends in Immunology
Author(s): Thomas Doebel, Benjamin Voisin, Keisuke Nagao
Our assumptions on the identity and functions of Langerhans cells (LCs) of the epidermis have undergone considerable changes. Once thought to be prototypic representatives of the dendritic cell (DC) lineage, they are now considered to be a specialized subset of tissue-resident macrophages. Despite this, LCs display a remarkable mixture of properties. Like many tissue macrophages, they self-maintain locally. However, unlike tissue macrophages and similar to DCs, they homeostatically migrate to lymph nodes and present antigen to antigen-specific T cells. Current evidence indicates that the immune responses initiated by LCs are complex and dependent on antigenic properties and localization of the stimulus. This complexity is reflected in the recently demonstrated roles of LCs in type 17, regulatory, and humoral immune responses.

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Therapeutic effect of capsaicin nasal treatment in patients with mixed rhinitis unresponsive to intranasal steroids

Abstract

Literature is convincing regarding the efficacy of capsaicin nasal treatment in idiopathic rhinitis (IR). However, up to 50% of IR patients do not meet the strict inclusion criteria of the trials conducted so far. As a consequence, the efficacy of capsaicin is unknown in a significant number of IR patients that do not meet the strict inclusion/exclusion criteria (1)(2). 'Mixed rhinitis' (MR) patients have more than one major etiologic factor involved in the mucosal pathology. We have no idea about the efficacy of capsaicin nasal spray in these patients nor about the time interval to seek a second application. We report here that capsaicin nasal spray is effective in a broader group of IR than the purely selected ones described before, that subjective nasal hyperreactivity is a good predictor of positive outcome and that the time interval for seeking a second treatment is likely to be shorter in MR patients than in the strictly selected IR patients.

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Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid-treated eosinophilic esophagitis

Abstract

Background

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil-predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in EoE patients is owing to pre-existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid (CS) therapy.

Methods

Medical histories, as well as serum and tissue samples of 60 EoE patients (15 CS-naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database (SEED) and Biobank, were analyzed. We applied ImmunoCAP to measure IgE levels and immunofluorescence techniques to examine epithelial barrier components.

Results

EoE patients had higher total IgE levels and were more frequently sensitized to Candida albicans than controls. In EoE tissue specimens, increased numbers of eosinophils and mast cells, a higher expression levels of thymic stromal lymphopoietin (TSLP), cathelicidin, proteases, i.e. the kallikreins (KLK)-5 and KLK-7, were observed as compared with controls, while reduced expression of lympho-epithelial Kazal-type-related inhibitor (LEKTI), filaggrin, E-cadherin, claudin, occludin, demoglein-1 was found, independent of CS therapy. In CS-treated EoE, significantly lower numbers of CD1a+ cells and cathelicidin expression were noted as compared to CS-naive EoE.

Conclusion

This study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote Candida albicans colonization and likely subsequent sensitization.

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Therapeutic effect of capsaicin nasal treatment in patients with mixed rhinitis unresponsive to intranasal steroids

Abstract

http://ift.tt/2ttOFet

Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid-treated eosinophilic esophagitis

Abstract

Background

Methods

Results

Conclusion

http://ift.tt/2tXmurv

Cover Image

The cover image, by Tetsuro Sekine et al., is based on the Original Article Local resectability assessment of head and neck cancer: Positron emission tomography/MRI versus positron emission tomography/CT, DOI: 10.1002/hed.24783.

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Issue Information - Contents

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Cover Image

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Issue Information - Contents

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Prognostic significance of recurrent additional chromosomal abnormalities in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Publication date: October 2017
Source:Cancer Genetics, Volumes 216–217
Author(s): Chang Ahn Seol, Young-Uk Cho, Seongsoo Jang, Chan-Jeoung Park, Jung-Hee Lee, Je-Hwan Lee, Kyoo Hyung Lee, Eul-Ju Seo
In Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL), additional chromosomal abnormalities (ACAs) are frequently observed. We investigated the cytogenetic characteristics and prognostic significance of ACAs in Ph-positive ALL. We reviewed the clinical data and bone marrow cytogenetic findings of 122 adult Ph-positive ALL patients. The ACAs were examined for partial or whole chromosomal gains or losses, and structural aberrations. The overall survival (OS) and disease-free survival (DFS) of patients who received hematopoietic cell transplantation were compared between the isolated Ph group and ACA group. ACAs were present in 73.0% of all patients. The recurrent ACAs were extra Ph (24.7%), 9/9p loss (20.2%), and 7/7p loss (19.1%). Complex karyotype was found in 28.1% of patients in the ACA group. Younger patients (19–30 years) in the ACA group showed the highest frequency of extra Ph (54%) compared to other age groups. The OS in the ACA group was significantly shorter than in the isolated Ph group. The presence of an extra Ph chromosome or 9/9p loss was significantly associated with shorter OS and DFS, whereas 7/7p loss and complex karyotype were not associated with poorer prognosis. We suggest that subclassification of ACAs could be applied to prognostic investigation of Ph-positive ALL.

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Groin Sentinel Node Biopsy and 18F-FDG PET/CT-supported preoperative lymph node assessment in cN0 patients with vulvar cancer currently unfit for minimally invasive inguinal surgery: The GroSNaPET study

Publication date: Available online 16 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Giorgia Garganese, Angela Collarino, Simona M. Fragomeni, Vittoria Rufini, Germano Perotti, Stefano Gentileschi, Maria T. Evangelista, Francesco P. Ieria, Luca Zagaria, Sonia Bove, Alessandro Giordano, Giovanni Scambia
ObjectiveThe study aims were: 1) to verify the role of sentinel node biopsy (SNB) in a subset of patients with clinical N0 (cN0) invasive vulvar cancer (VC) who were still candidates for radical inguinal surgery according to the current guidelines; 2) to investigate whether a preoperative 18F-FDG PET/CT (PET/CT) evaluation could improve the selection of node negative patients.MethodsFrom July 2013 to July 2016, all patients with VC admitted to our Division were evaluated by standard imaging and clinical exam. Among the patients assessed as cN0 we enrolled those unsuitable for SNB, due to: T > 4 cm, multifocal tumors, complete tumor diagnostic excision, contralateral nodal involvement and local recurrence. A preoperative PET/CT was performed. For each patient surgery included SNB, performed using a combined technique (radiotracer plus blue dye), followed by standard inguino-femoral lymphadenectomy. The reference standard was histopathology.ResultsForty-seven patients entered the study for a total of 73 groins. Histopathology revealed 12 metastatic SNs in 9 groins. No false-negative SNs were found (NPV 100%). PET/CT showed a negative predictive value of 93%.ConclusionsOur data suggest that SNB is accurate and safe even in cN0 patients currently excluded from this procedure, providing that a careful preoperative selection is performed. PET/CT allows a reliable assessment of LN status and may be an effective support for the selection of patients who are safe candidates for SNB.

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Improved survival after retrieval of 12 or more regional lymph nodes in appendiceal cancer

Publication date: Available online 15 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Isabella Fleischmann, Rene Warschkow, Ulrich Beutner, Lukas Marti, Bruno M. Schmied, Thomas Steffen
BackgroundTo evaluate the role of regional lymph node (RLN) retrieval on stage migration, overall (OS), and cancer-specific survival (CSS) in appendiceal cancer.MethodsBetween 2004 and 2012, 1046 patients with primary stage I-III carcinoma of the appendix were identified in the Surveillance, Epidemiology and End Results database. The impact of the number of RLN removed on OS and CSS was assessed using joinpoint regression, Cox regression, and propensity score methods.ResultsThe rate of node-positive cancer increased with the number of retrieved RLN from 10.5% in patients with one RLN removed to 30.6% in patients with 10 RLNs removed. This leveling off at 10 RLN was confirmed by joinpoint regression analysis (p=0.023).Despite the finding that retrieval of 10 RLN should be sufficient for appendiceal cancer, for the survival analysis the somewhat higher cutoff of 12 RLN was applied, since this cutoff is recommended by the guidelines for colorectal cancer. Retrieval of 12 or more RLN was beneficial compared to less than 12 RLN retrieved for OS (HR=0.60, p<0.001) and CSS (HR=0.67, p=0.020) in multivariable analysis, as well as in propensity score matched analysis (OS: HR=0.58, p=0.001, CSS: HR=0.61, p=0.005).ConclusionThe rate of node-positive cancer increased with the number of retrieved RLN up to about 10 RLN (95%CI: 3.6 to 16.3, p=0.023). Over 10 retrieved RLN, the node-positive cancer rate no longer increased. This correlates with the recommended number of 12 RLN to be retrieved in colorectal cancer, but differs from the guideline for neuroendocrine tumors.

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Do some epithelial ovarian cancers originate from a fallopian tube ciliate cell lineage?

Publication date: Available online 16 July 2017
Source:Medical Hypotheses
Author(s): Jan Rohozinski, Conception Diaz-Arrastia, Creighton L. Edwards
There is a general agreement that a large subpopulation of serous ovarian cancers arise from the fallopian tube mucosal epithelium. However, there is still some debate as to whether the cancers originate from a secretory or ciliate cell lineage. One well established method for determining the origin of a cell line is to document the expression of genes and proteins that are cell type specific. Lineage or tissue specific patterns of gene expression are evidence of direct decent from a given cell type within a tissue. It has recently been established that the Tumor Protein TAp73 gene (TP73) is expressed in basal epithelial cells that develop into multiciliate cells. TP73 expression is therefore a marker for basal stem cells that are predestined to differentiate into cells with motile cilia and its expression is maintained in fully differentiated multiciliate cells. Interestingly TP73 expression has also been observed in a high percentage of epithelial ovarian cancers. With this in mind, it is hypothesized that a high percentage of epithelial ovarian cancers which express TP73 originate from a ciliate cell lineage.

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Decreased Use of Spatial Pattern Separation in Contemporary Lifestyles May Contribute to Hippocampal Atrophy and Diminish Mental Health

Publication date: Available online 15 July 2017
Source:Medical Hypotheses
Author(s): Birkel LP
The spatial pattern separation process has not yet been proposed as a pivotal neural activity affecting hippocampal volume, a metric of mental health. The dentate gyrus/CA3 region is increasingly implicated in hippocampal atrophy and its putative role in spatial pattern separation is impaired in mental health disorders. Spatial pattern separation is thought to utilize the heightened neural plasticity of newborn neurons in the dentate gyrus to distinguish highly similar aspects of scene so that these remain distinct in memory rather than lost. The level of such activity associates with BDNF secretion, which may affect neuroplasticity and therefore hippocampal volume. Distinguishing fine-grained aspects of surroundings was likely of great importance during hunting and gathering for survival in nature. However the need to make subtle environmental discriminations is much reduced in modern survival activity. Ancestrally, exploration and utilization of the spatial pattern separation process may have resulted in detection of potential food items, an activity that was likely followed by intensive effort-based reward (EBR) activity to obtain the food. EBR activity and restorative walking in nature demonstrate positive mental health benefits, while their lack indicates negative effects on mental health. Data support the hypothesis that spatial pattern separation activity and neural circuitry are separate from, and may precede, those of EBR as well as restorative walking in nature. Spatial pattern separation therefore represents an additional nature-related neural process whose modern decrease in use may negatively affect mental health. Interventions that increase spatial pattern separation experiences may enhance BDNF secretion, hippocampal volume and mental health.

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Tumor-associated immune aggregates in oral cancer: their cellular composition and potential prognostic significance

Publication date: Available online 16 July 2017
Source:Medical Hypotheses
Author(s): Maria Luiza Diniz de Sousa Lopes, Yi Liu, Kelly Yi-Ping Liu, Éricka Janine Dantas da Silveira, Catherine F. Poh
There is growing evidence supporting the importance of immune microenvironment in cancer development and progression, especially with the rapid development of immunotherapy. Presence of immune cell aggregates in solid tumors has been associated with clinical outcomes, but little is known about the immune microenvironment in oral squamous cell carcinoma (OSCC), which has high morbidity and mortality. Based on our preliminary observation, we hypothesize that there is the presence of tumor-associated immune aggregates (TaIAs) during oral cancer development. Adapting to the dynamic change of the composition of cellular membership and co-evolving with the tumor at invasion fronts, these TaIAs, either pro-inflammatory or immune suppressive, are associated with clinical consequences. With the unique access to a set of prospectively collected, highly annotated OSCC surgical samples and the use of multi-color immunostaining of key immune cells, the confirmation of our hypothesis may shed light of the underlying biology related to OSCC and the knowledge learned can potentially be used to identify prognostic markers, response predictive markers for immunotherapies, as well as novel therapeutic targets.

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IgA nephropathy during treatment with TNF-alpha blockers: could it be predicted?

Publication date: Available online 16 July 2017
Source:Medical Hypotheses
Author(s): Vito Di Lernia
Immunoglobulin A (IgA) nephropathy (IgAN) may sometimes be related to exposure to pharmacological agents, among which anti-Tumor Necrosis Factor (TNF)-alpha agents. The characteristic pathological feature is a deposition of IgA-containing immune complexes in vessel walls in the kidney mesangium. The link between TNF-alpha blockers and IgAN may be hypothesized examining diseases which share pathologic features. In this respect, idiopathic IgAN and Henoch Schonlein Purpura have been the object of studies revealing a pathogenetic role of aberrant glycosylation of IgA1 molecules. The Authors suggest that anti-drug antibodies against glycan structures of TNF-alpha inhibitors may cross react against serum aberrant IgA1 leading to large antigen-antibody complexes. These large polymeric IgA complexes are then able to deposit in the mesangium and activate the complement cascade. Such hypothesis may be tested by measuring serum levels of galactose-deficient IgA1 of patients developing IgAN following introduction of TNF-alpha blockers. Such a test would be useful also before administration of anti-TNF alpha agents. The presence of aberrant IgA1 may represent a contraindication for treatment with TNF blockers.

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Syntrophic Imbalance and the Etiology of Bacterial Endoparasitism Diseases

Publication date: Available online 15 July 2017
Source:Medical Hypotheses
Author(s): James F. White
This article outlines the proposed 'syntrophic imbalance hypothesis' for etiology of bacterial endoparasitism diseases. This hypothesis involves microbes (archaea and bacteria) that exist in human body biofilms in syntrophic associations, where bacteria ferment nutrients to produce short chain fatty acids (SCFAs) that are used by methanogenic archaeons to produce methane. Overgrowth of archaea on human tissues (e.g., in association with intestines, teeth or lungs) results in excessive removal of SCFAs from the biofilms and this triggers bacteria in the free-living biofilm state to convert to the endoparasitic state and become intracellular in host cells where they incite inflammation and disease. The proposed model provides the mechanism to explain dysbiosis etiology of several human diseases, including gingivitis, leaky gut syndrome, Crohn's disease, irritable bowel syndrome, among others.

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Outcomes of oral cavity cancer patients treated with surgery followed by postoperative intensity modulated radiation therapy

Publication date: September 2017
Source:Oral Oncology, Volume 72
Author(s): Sean R. Quinlan-Davidson, Abdallah S.R. Mohamed, Jeffrey N. Myers, Gary B. Gunn, Faye M. Johnson, Heath Skinner, Beth M. Beadle, Ann M. Gillenwater, Jack Phan, Steven J. Frank, William N. William, Andrew J. Wong, Stephen Y. Lai, Clifton D. Fuller, William H. Morrison, David I. Rosenthal, Adam S. Garden
ObjectivesAlthough treatment paradigms have not changed significantly, radiotherapy, surgery, and imaging techniques have improved, leading us to investigate oncologic and survival outcomes for oral cavity squamous cell cancer (OCSCC) patients treated with surgery followed by postoperative IMRT.Material and methodsRecords of patients with pathological diagnosis of OCSCC treated between 2000 and 2012 were retrospectively reviewed. Patients' demographic, disease, and treatment criteria were extracted. Kaplan-Meier method was used to calculate survival curves.ResultsTwo hundred eighty-nine patients were analyzed. Median follow-up was 35months. Two hundred sixty-eight had neck dissections (93%), of which 66% had nodal involvement, and 51% of those positive dissections had extracapsular extension. Forty patients received induction chemotherapy and 107 received concurrent chemotherapy. Median dose to high risk clinical target volume was 60Gy/30 fractions. The 5-year locoregional control and overall survival rates were 76% and 57%, respectively. Tumors with >1.5cm depth of invasion had significantly higher risk of local failure compared with ≤1.5cm (p<0.001). In multivariate analysis, positive and no neck dissection (p=0.01), positive lymphovascular invasion (p=0.006) and >1.5cm depth of invasion (p=0.003) were independent predictors of poorer survival.ConclusionsDisease outcomes were consistent with historical data and did not appear compromised by the use of IMRT.

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Incidence of, and risk factors for, mandibular osteoradionecrosis in patients with oral cavity and oropharynx cancers

Publication date: September 2017
Source:Oral Oncology, Volume 72
Author(s): Dominic H. Moon, Sung Ho Moon, Kyle Wang, Mark C. Weissler, Trevor G. Hackman, Adam M. Zanation, Brian D. Thorp, Samip N. Patel, Jose P. Zevallos, Lawrence B. Marks, Bhishamjit S. Chera
ObjectivesTo evaluate the incidence of, and risk factors associated with, mandibular osteoradionecrosis (MORN) following radiation therapy (RT) for oral cavity and oropharyngeal cancers.Materials and MethodsPatient and treatment records of 252 consecutive patients with oral cavity or oropharynx cancers treated with RT by a single radiation oncologist at a high volume academic institution from August 2009 to December 2015 were retrospectively reviewed. A Cox regression model was used to assess factors associated with the development of MORN. RT dosimetry was compared between patients with MORN and a matched cohort of patients without MORN.ResultsMORN developed in 14 patients (5.5%), occurring 3–40 (median 8) months post-RT. Factors associated with MORN on univariable analysis included primary diagnosis of oral cavity vs oropharynx cancer (hazard ratio [HR]: 3.0, p=0.04), smoking at the time of RT (HR: 3.1, p=0.04), mandibular invasion of the primary (HR: 3.7, p=0.04), pre-RT tooth extraction (HR: 4.52, p=0.01), and treatment with 3D-conformal RT vs intensity-modulated RT (HR: 5.1, p=0.003). On multivariable analysis, pre-RT tooth extractions and RT technique remained significant. A dosimetric comparison between patients with and without MORN showed no significant differences.Conclusions and RelevanceThe incidence of MORN is low in the modern era at a high volume academic center. Modifiable risk factors including pre-RT tooth extractions, smoking, and RT technique are associated with MORN, and the risk should be minimized with appropriate dental evaluation and treatment, smoking cessation efforts, and the use of intensity-modulated RT.

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Transoral robotic total laryngopharyngectomy and free jejunal flap reconstruction for hypopharyngeal cancer

Publication date: Available online 15 July 2017
Source:Oral Oncology
Author(s): Jimmy Yu Wai Chan, Richie Chiu Lung Chan, Velda Ling Yu Chow, Raymond King Ying Tsang, Stanley Thian Sze Wong, William Ignace Wei
BackgroundTo report on the feasibility of total laryngopharyngectomy and free jejunal flap transfer for patient with hypopharyngeal cancer via the transoral robotic surgery (TORS) approach.Material and methodsA patient with hypopharyngeal cancer involving the post-cricoid region is used for demonstration of the TORS total laryngopharyngectomy and free jejunal flap reconstruction.ResultsThe procedure starts with a cruciate incision for terminal tracheostomy. The trachea and cervical esophagus is exposed and transected, making sure that the resection margins are adequate. This is followed by the transoral dissection using the robotic surgical system. The laryngopharyngectomy specimen is delivered and the free jejunal flap is replaced transorally. Jejuno-oesophageal suturing and the microvascular anastomosis are performed through the tracheostomy wound. The remaining pharyngo-jejunal anastomosis is performed transorally via the TORS approach.ConclusionTORS total laryngopharyngectomy and free jejunal flap reconstruction is feasible and provides and alternative option to the traditional transcervical approach.

http://ift.tt/2trqMUy

Discovery of potent molecular chimera (CM358) to treat human metastatic melanoma.

Discovery of potent molecular chimera (CM358) to treat human metastatic melanoma.

Eur J Med Chem. 2017 Jun 29;138:602-615

Authors: Gilad Y, Tuchinsky H, Ben-David G, Minnes R, Gancz A, Senderowitz H, Luboshits G, Firer MA, Gellerman G

Abstract
The resistance of cancer cells to chemotherapeutic agents, whether through intrinsic mechanisms or developed resistance, motivates the search for new chemotherapeutic strategies. In the present report, we demonstrate a facile synthetic strategy towards the discovery of new anti-cancer substances. This strategy is based on simple covalent coupling between known anti-cancer drugs, which results in novel 'chimeric' small molecules. One of these novel compounds, CM358, is the product of an amide bond formation between the known Topoisomerase II (Topo II) inhibitor amonafide (AM) and the known DNA mustard alkylator chlorambucil (CLB). It demonstrates significant enhanced cytotoxicity over an equimolar mixture of AM and CLB in various cancer cell lines and in a xenograft model of human metastatic melanoma. Topo II inhibition as well as in silico docking studies suggest that CM358 is a stronger Topo II binder than AM. This may be attributed, at least partially, to the placement of the CLB moiety in a favorable orientation with respect to DNA cross-linking with nearby guanines. In a human metastatic melanoma (WM 266-4) xenograft model, this compound was profoundly superior to a mixture of AM and CLB in reduction of tumor growth, maintenance of body weight and extension of overall survival.

PMID: 28710962 [PubMed - as supplied by publisher]

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Characterization of Potent and Selective Iodonium-Class Inhibitors of NADPH Oxidases.

Characterization of Potent and Selective Iodonium-Class Inhibitors of NADPH Oxidases.

Biochem Pharmacol. 2017 Jul 11;:

Authors: Lu J, Risbood P, Kane CT, Hossain MT, Anderson L, Hill K, Monks A, Wu Y, Antony S, Juhasz A, Liu H, Jiang G, Harris E, Roy K, Meitzler JL, Konaté M, Doroshow JH

Abstract
The NADPH oxidases (NOXs) play a recognized role in the development and progression of inflammation-associated disorders, as well as cancer. To date, several NOX inhibitors have been developed, through either high throughput screening or targeted disruption of NOX interaction partners, although only a few have reached clinical trials. To improve the efficacy and bioavailability of the iodonium class NOX inhibitor diphenylene iodonium (DPI), we synthesized 36 analogs of DPI, focusing on improved solubility and functionalization. The inhibitory activity of the analogs was interrogated through cell viability and clonogenic studies with a colon cancer cell line (HT-29) that depends on NOX for its proliferative potential. Lack of altered cellular respiration at relevant iodonium analog concentrations was also demonstrated. Additionally, inhibition of ROS generation was evaluated with a luminescence assay for superoxide, or by Amplex Red(®) assay for H2O2 production, in cell models expressing specific NOX isoforms. DPI and four analogs (NSCs 740104, 751140, 734428, 737392) strongly inhibited HT-29 cell growth and ROS production with nanomolar potency in a concentration-dependent manner. NSC 737392 and 734428, which both feature nitro functional groups at the meta position, had >10-fold higher activity against ROS production by cells that overexpress dual oxidase 2 (DUOX2) than the other compounds examined (IC50 ≈ 200-400 nM). Based on these results, we synthesized and tested NSC 780521 with optimized potency against DUOX2. Iodonium analogs with anticancer activity, including the first generation of targeted agents with improved specificity against DUOX2, may provide a novel therapeutic approach to NOX-driven tumors.

PMID: 28709950 [PubMed - as supplied by publisher]

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Lessons Learned from Two Decades of Anticancer Drugs.

Lessons Learned from Two Decades of Anticancer Drugs.

Trends Pharmacol Sci. 2017 Jul 11;:

Authors: Liu Z, Delavan B, Roberts R, Tong W

Abstract
Tremendous efforts have been made to elucidate the basis of cancer biology with the aim of promoting anticancer drug development. Especially over the past 20 years, anticancer drug development has developed from conventional cytotoxic agents to target-based and immune-related therapies. Consequently, more than 200 anticancer drugs are available on the market. However, anticancer drug development still suffers high attrition during the later phases of clinical development and is considered to be a difficult and risky therapeutic category within the drug development arena. The disappointing performance of investigational anticancer candidates implies that there are some shortcomings in the translation of preclinical in vitro and in vivo models to humans, and that heterogeneity in the patient population presents a significant challenge. Here, we summarize both successful and failed experiences in anticancer development during the past 20 years and help identify why the current paradigm may be suboptimal. We also offer potential strategies for improvement.

PMID: 28709554 [PubMed - as supplied by publisher]

http://ift.tt/2tfMkZg

Broad-range potential of Asphodelus microcarpus leaves extract for drug development.

Broad-range potential of Asphodelus microcarpus leaves extract for drug development.

BMC Microbiol. 2017 Jul 14;17(1):159

Authors: Di Petrillo A, Fais A, Pintus F, Santos-Buelga C, González-Paramás AM, Piras V, Orrù G, Mameli A, Tramontano E, Frau A

Abstract
BACKGROUND: Many plants have been used in traditional medicine for their antibacterial, antifungal, antiprotozoal, antiviral, antidiarrhoeal, analgesic, antimalarial, antioxidant, anti-inflammatory and anticancer activities. In order to find novel antimicrobial and antiviral agents, the aim of the present study was the evaluation of the antibacterial and antibiofilm susceptibility of Asphodelus microcarpus leaves extract. Moreover, the antiviral activity and the phytochemical composition of the active extract were also determined.
METHODS: Antimicrobial and antibiofilm activities of leaves ethanol extract of A. microcarpus were evaluated on 13 different microbial strains. We selected three different sets of microorganisms: (i) Gram-positive bacteria, (ii) Gram-negative bacteria and (iii) yeasts. The potential antiviral activity of A. microcarpus leaves ethanol extract was evaluated with a luciferase reporter gene assay in which the dsRNA-dependent RIG-I-mediated IFN-β activation was inducted or inhibited by the Ebola virus VP35 protein. HPLC-DAD-MS was used to identify phenolic profile of the active extract.
RESULTS: A. microcarpus leaves extract showed a potent inhibitory activity on Gram-positive bacteria while only a reduced inhibition was observed on Gram-negative bacteria. No activity was detected against Yeasts. The extract also showed an interesting antibiofilm motif on various bacterial strains (E. coli, S. aureus, S. haemolyticus and B. clausii). Moreover, this extract significantly affected the Ebola virus VP35 inhibition of the viral RNA (vRNA) induced IFN response.
CONCLUSIONS: The overall results provide supportive data on the use of A. microcarpus as antimicrobial agent and a potential source of anti-viral natural products. Data collected set the bases for further studies for the identification of single active components and the development of new pharmaceuticals.

PMID: 28709400 [PubMed - in process]

http://ift.tt/2tYxPG8

Risk of treatment-related mortality in cancer patients treated with ipilimumab: A systematic review and meta-analysis

Publication date: September 2017
Source:European Journal of Cancer, Volume 83
Author(s): Sheng Zhang, Fei Liang, Wenfeng Li, Qing Wang
BackgroundFatal adverse events (FAEs) have been reported in cancer patients receiving ipilimumab—a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, but the risk of treatment-related mortality is unknown. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) of ipilimumab to determine the overall risk of FAEs associated with ipilimumab.MethodsWe systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, ClinicalTrial.gov and conference proceedings from inception to December 2016, for prospective trials that randomly assigned patients to ipilimumab treatment (with or without concurrent therapy) or controls with available data regarding incidence of FAEs. Two reviewers extracted data independently. Incidence of FAEs was pooled using a random effects model, and the risk of FAEs associated with ipilimumab was estimated using Peto odds ratios (ORs).ResultsA total of 5775 patients with solid tumours included in 12 RCTs (10 from journal reports and 2 from ClinicalTrials.gov) were included in the meta-analysis. The pooled incidence of FAEs for patients treated with ipilimumab was 1.13% (95% confidence interval [CI], 0.56–1.86), compared with 0.22% in the control arms. Ipilimumab was associated with statistically significantly increased risk of FAEs, with a pooled Peto OR of 2.3 (95% CI, 1.4–3.6; P < 0.001). Analyses according to cancer type (melanoma versus other cancers); treatment mode (combination therapy or monotherapy); control type (active control versus placebo/best supportive care only); ipilimumab dose (high versus low dose [10 versus 3 mg/kg every 3 weeks]) found no statistically significantly differential effect by subgroups. Among the specific causes of FAEs, ipilimumab was associated with an increased risk of fatal gastrointestinal toxicity, with an OR of 4.5 (95% CI, 1.5–13.6).ConclusionThe use of ipilimumab, compared with controls, was associated with increased risk of treatment-related mortality.

http://ift.tt/2ttdabw

A Unique Case for Spinal Cord Stimulation: Successful Treatment of Small Fiber Neuropathy Pain Using Multiple Spinal Cord Stimulators

Spinal cord stimulators have commonly been used to treat multiple pain conditions. This case report represents a unique case of using multiple spinal cord stimulators for widespread small fiber neuropathy pain. This case report concerns patient JJ who first presented with generalized neuropathic pain. His pain was an intermittent burning, stinging quality that originally focused in both of his feet and progressed to include his legs and arms and eventually involved his entire body. The pain would last moments to hours at least daily. He reported a poor quality of life. He was diagnosed with small fiber neuropathy with anhydrosis, suggestive of idiopathic erythromelalgia. He had a spinal cord stimulator trial involving both cervical and lower thoracic percutaneous leads. After two spinal cord stimulators were implanted, the patient began to report an improvement in pain. The patient continues to report excellent pain relief. The patient uses the stimulator intermittently as needed, in an abortive fashion for pain flares. The patient is very pleased and has increased his activity. He now attends graduate school full time. This case report hopes to illustrate a unique use of multiple spinal cord stimulators in treating widespread neuropathic pain caused by small fiber neuropathy.

http://ift.tt/2tt9eaL

Interaction between prenatal risk and infant parasympathetic and sympathetic stress reactivity predicts early aggression

Publication date: Available online 15 July 2017
Source:Biological Psychology
Author(s): J. Suurland, K.B. Van der Heijden, S.C.J. Huijbregts, S.H.M. Van Goozen, H. Swaab
Nonreciprocal action of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increases susceptibility to emotional and behavioral problems in children exposed to adversity. Little is known about the PNS and SNS in interaction with early adversity during infancy. Yet this is when the physiological systems involved in emotion regulation are emerging and presumably most responsive to environmental influences. We examined whether parasympathetic respiratory sinus arrhythmia (RSA) and sympathetic pre-ejection period (PEP) response and recovery at six months, moderate the association between cumulative prenatal risk and physical aggression at 20 months (N=113). Prenatal risk predicted physical aggression, but only in infants exhibiting coactivation of PNS and SNS (i.e., increase in RSA and decrease in PEP) in response to stress. These findings indicate that coactivation of the PNS and SNS in combination with prenatal risk is a biological marker for the development of aggression.

http://ift.tt/2untGP3

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Κυριακή 16 Ιουλίου 2017

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