Parameters of Instrumental Swallowing Evaluations: Describing a Diagnostic Dilemma

Abstract

The aim of this study was to compare selected parameters of two swallow evaluations: fiberoptic endoscopic evaluation of swallowing (FEES) and the modified barium swallow (MBS) study. This was a cross-sectional, descriptive study. Fifty-five clinicians were asked to watch video recordings of swallow evaluations of 2 patients that were done using fluoroscopy and endoscopy simultaneously. In a randomized order, clinicians viewed 4 edited videos from simultaneous evaluations: the FEES and MBS videos of patient 1 and 2 each taking one swallow of 5 mL applesauce. Clinicians filled out a questionnaire that asked (1) which anatomical sites they could visualize on each video, (2) where they saw pharyngeal residue after a swallow, (3) their overall clinical impression of the pharyngeal residue, and (4) their opinions of the evaluation styles. Clinicians reported a significant difference in the visualization of anatomical sites, 11 of the 15 sites were reported as better-visualized on the FEES than on the MBS video (p < 0.05). Clinicians also rated residue to be present in more locations on the FEES than on the MBS. Clinicians' overall impressions of the severity of residue on the same exact swallow were significantly different depending on the evaluation type (FEES vs. MBS for patient 1 χ2 = 20.05, p < 0.0001; patient 2 χ2 = 7.52, p = 0.006), with FEES videos rated more severely. FEES advantages were: more visualization of pharyngeal and laryngeal swallowing anatomy and residue. However, as a result, clinicians provided more severe impressions of residue amount on FEES. On one hand, this suggests that FEES is a more sensitive tool than MBS studies, but on the other hand, clinicians might provide more severe interpretations on FEES.

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MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

Abstract

Glioma is a severe and highly lethal brain cancer, a malignancy largely stemming from growing in a relatively restrained area of the brain. Hence, the understanding of the molecular regulation of the growth of glioma is critical for improving its treatment. MicroRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. However, the molecular function and mechanisms of miR-508-5p in gliomagenesis are still unclear. The aim of this study was to investigate miR-508-5p expression in glioma and determine its effects on proliferation. miR-508-5p expression levels, both in glioma cell lines and in tissue, were significantly lower than in a normal human astrocyte cell line or adjacent tissues. Cell growth was analyzed using a MTT assay and over-expression of miR-508-5p was found to decrease glioma cell growth. Moreover, a bioinformatic analysis was performed, showing that glycoprotein non-metastatic melanoma B (GPNMB) was a direct target for miR-508-5p in glioma cells. Furthermore, in vivo treatment with miR-508-5p reduced GPNMB protein levels in the tumor. Additionally, overexpression of GPNMB without 3′-UTR partially reversed the cell growth arrest induced by miR-508-5p over-expression in glioma cells. In conclusion, these results indicate that increased expression of miR-508-5p might be related to glioma progression, indicating a potential role of miR-508-5p for clinical therapy.

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A Novel Supra-Brow Combined with Infra-Brow Lift Approach for Asian Women

Abstract

Background

Direct brow lift surgery remains popular among Asian women despite its disadvantages. The traditional direct brow lift by a supra-brow incision is not suitable for Asian women because of their unique facial features, such as higher eyebrows, wider upper eyelids, and more orbital fat. Therefore, we designed a novel brow lift technique via a supra-brow combined with an infra-brow approach for Asian women.

Methods

An area of skin above and below the eyebrow was measured, demarcated, and surgically removed. The redundant orbicularis oculi muscle (OOM) was excised while keeping the frontalis muscle intact. The OOM in the inferior flap was elevated and sutured to the frontalis muscle. In cases of puffy eyelids, orbital fat was partially removed through an infra-brow incision. Finally, a series of modifications were performed to reduce post-operative scarring.

Results

A total of 496 patients underwent this surgery from July 2009 to December 2013 and 432 patients were followed up for at least 6 months after surgery. Post-operative scars, in most patients (428/432), were inconspicuous. There were no facial nerve injuries documented and eight patients reported transient forehead numbness. The height of the palpebral fissure was increased but there was no marked increase observed of the distance between the upper eyelid edge and the eyebrow. In follow-up visits, 409 out of 432 patients (94.7 %) were satisfied with their surgical results.

Conclusions

This new brow lift technique via a supra-brow combined with an infra-brow approach provided a simple and safe surgical repair of lateral brow ptosis, upper eyelids hooding, and crows' feet in Asian women. The surgical outcomes were predictable and the scars were inconspicuous.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

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Nitrosative Stress in the Nervous System: Guidelines for Designing Experimental Strategies to Study Protein S-Nitrosylation

Abstract

Reactive nitrogen species, such as nitric oxide (NO), exert their biological activity in large part through post-translational modification of cysteine residues, forming S-nitrosothiols. This chemical reaction proceeds via a process that we and our colleagues have termed protein S-nitrosylation. Under conditions of normal NO production, S-nitrosylation regulates the activity of many normal proteins. However, in degenerative conditions characterized by nitrosative stress, increased levels of NO lead to aberrant S-nitrosylation that contributes to the pathology of the disease. Thus, S-nitrosylation has been implicated in a wide range of cellular mechanisms, including mitochondrial function, proteostasis, transcriptional regulation, synaptic activity, and cell survival. In recent years, the research area of protein S-nitrosylation has become prominent due to improvements in the detection systems as well as the demonstration that protein S-nitrosylation plays a critical role in the pathogenesis of neurodegenerative and other neurological disorders. To further promote our understanding of how protein S-nitrosylation affects cellular systems, guidelines for the design and conduct of research on S-nitrosylated (or SNO-)proteins would be highly desirable, especially for those newly entering the field. In this review article, we provide a strategic overview of designing experimental approaches to study protein S-nitrosylation. We specifically focus on methods that can provide critical data to demonstrate that an S-nitrosylated protein plays a (patho-)physiologically-relevant role in a biological process. Hence, the implementation of the approaches described herein will contribute to further advancement of the study of S-nitrosylated proteins, not only in neuroscience but also in other research fields.

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Adhesion molecules and the extracellular matrix as drug targets for glioma

Abstract

The formation of tumor vasculature and cell invasion along white matter tracts have pivotal roles in the development and progression of glioma. A better understanding of the mechanisms of angiogenesis and invasion in glioma will aid the development of novel therapeutic strategies. The processes of angiogenesis and invasion cause the production of an array of adhesion molecules and extracellular matrix (ECM) components. This review focuses on the role of adhesion molecules and the ECM in malignant glioma. The results of clinical trials using drugs targeted against adhesion molecules and the ECM for glioma are also discussed.

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Effect of propofol and sevoflurane on the inflammatory response of patients undergoing craniotomy

Abstract

Background

The purpose of this randomised, single-centre study was to prospectively investigate the impact of anaesthetic techniques for craniotomy on the release of cytokines IL-6, IL-8, IL-10, and to determine whether intravenous anaesthesia compared to inhalational anaesthesia attenuates the inflammatory response.

Methods

The study enroled 40 patients undergoing craniotomy, allocated into two equal groups to receive either sevoflurane (n = 20) or propofol (n = 20) in conjunction with remifentanil and rocuronium. The lungs were ventilated mechanically to maintain normocapnia. Remifentanil infusion was adjusted according to the degree of surgical manipulation and increased when mean arterial pressure and the heart rate increased by more than 30 % from baseline. The depth of anaesthesia was adjusted to maintain a bispectral index (BIS) of 40–60. Invasive haemodynamic monitoring was used. Serum levels of IL-6, IL-8 and IL-10 were measured before surgery and anaesthesia, during tumour removal, at the end of surgery, and at 24 and 48 h after surgery. Postoperative complications (pain, vomiting, changes in blood pressure, infection and pulmonary, cardiovascular and neurological events) were monitored during the first 15 days after surgery.

Results

Compared with patients anaesthetised with sevoflurane, patients who received propofol had higher levels of IL-10 (p = 0.0001) and lower IL-6/IL-10 concentration ratio during and at the end of surgery (p = 0.0001). Both groups showed only a minor response of IL- 8 during and at the end of the surgery (p = 0.57).

Conclusions

Patients who received propofol had higher levels of IL-10 during surgery. Neither sevoflurane nor propofol had any significant impact on the occurrence of postoperative complications. Our findings should incite future studies to prove a potential medically important anti-inflammatory role of propofol in neuroanaesthesia.

Clinical trial registration

Identified as NCT02229201 at http://ift.tt/PmpYKN

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Does mandibular osteotomy affect gonial angle in patients with class III deformity? Vertical ramus osteotomy versus sagittal split osteotomy

Publication date: Available online 22 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): R. Tabrizi, H. Pakshir, H. Behnia, S. Akhlaghi, N. Shahsavari
The mandibular angle represents an important part of facial aesthetics. Mandibular osteotomy can affect the gonial angle. The aim of this study was to compare the effects of sagittal split osteotomy (SSO) and intraoral vertical ramus osteotomy (IVRO) on the gonial angle. This retrospective cohort study assessed subjects with mandibular prognathism who underwent SSO (group 1) or IVRO (group 2). Lateral cephalograms obtained before and 1 year after the osteotomies were analyzed. In this study, age, sex, the change in occlusal plane (OP) and mandibular plane (MP) angles, and the amount of mandibular setback were considered as variable factors, while the type of surgery (SSO or IVRO) was considered the predictive factor. Fifty-six subjects were studied: 26 in group 1 and 30 in group 2. The changes in MP angle and OP angle were not significantly different between the groups (P>0.05). The change in gonial angle was 6.07±4.46° in group 1 and 7.33±5.73° in group 2; assessment of the data did not demonstrate a significant difference between the two groups studied (P=0.53). Mandibular osteotomy (SSO or IVRO) may change the gonial angle, but a significant difference between SSO and IVRO was not detected.

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Probenecid and N-Acetylcysteine Prevent Loss of Intracellular Glutathione and Inhibit Neuronal Death after Mechanical Stretch Injury In Vitro

Journal of Neurotrauma , Vol. 0, No. 0.

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A Novel Supra-Brow Combined with Infra-Brow Lift Approach for Asian Women

Abstract

Background

Direct brow lift surgery remains popular among Asian women despite its disadvantages. The traditional direct brow lift by a supra-brow incision is not suitable for Asian women because of their unique facial features, such as higher eyebrows, wider upper eyelids, and more orbital fat. Therefore, we designed a novel brow lift technique via a supra-brow combined with an infra-brow approach for Asian women.

Methods

An area of skin above and below the eyebrow was measured, demarcated, and surgically removed. The redundant orbicularis oculi muscle (OOM) was excised while keeping the frontalis muscle intact. The OOM in the inferior flap was elevated and sutured to the frontalis muscle. In cases of puffy eyelids, orbital fat was partially removed through an infra-brow incision. Finally, a series of modifications were performed to reduce post-operative scarring.

Results

A total of 496 patients underwent this surgery from July 2009 to December 2013 and 432 patients were followed up for at least 6 months after surgery. Post-operative scars, in most patients (428/432), were inconspicuous. There were no facial nerve injuries documented and eight patients reported transient forehead numbness. The height of the palpebral fissure was increased but there was no marked increase observed of the distance between the upper eyelid edge and the eyebrow. In follow-up visits, 409 out of 432 patients (94.7 %) were satisfied with their surgical results.

Conclusions

This new brow lift technique via a supra-brow combined with an infra-brow approach provided a simple and safe surgical repair of lateral brow ptosis, upper eyelids hooding, and crows' feet in Asian women. The surgical outcomes were predictable and the scars were inconspicuous.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

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Session posters

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Perforator anatomy of the radial forearm free flap versus the ulnar forearm free flap for head and neck reconstruction

Publication date: Available online 21 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): D.D. Hekner, T.A.P. Roeling, E.M. Van Cann
The aim of this study was to investigate the vascular anatomy of the distal forearm in order to optimize the choice between the radial forearm free flap and the ulnar forearm free flap and to select the best site to harvest the flap. The radial and ulnar arteries of seven fresh cadavers were injected with epoxy resin (Araldite) and the perforating arteries were dissected. The number of clinically relevant perforators from the radial and ulnar arteries was not significantly different in the distal forearm. Most perforators were located in the proximal half of the distal one third, making this part probably the safest location for flap harvest. Close to the wrist, i.e. most distally, there were more perforators on the ulnar side than on the radial side. The ulnar artery stained 77% of the skin surface area of the forearm, showing the ulnar forearm free flap to be more suitable than the radial forearm free flap for the restoration of large defects.

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Effect of propofol and sevoflurane on the inflammatory response of patients undergoing craniotomy

Abstract

Background

The purpose of this randomised, single-centre study was to prospectively investigate the impact of anaesthetic techniques for craniotomy on the release of cytokines IL-6, IL-8, IL-10, and to determine whether intravenous anaesthesia compared to inhalational anaesthesia attenuates the inflammatory response.

Methods

The study enroled 40 patients undergoing craniotomy, allocated into two equal groups to receive either sevoflurane (n = 20) or propofol (n = 20) in conjunction with remifentanil and rocuronium. The lungs were ventilated mechanically to maintain normocapnia. Remifentanil infusion was adjusted according to the degree of surgical manipulation and increased when mean arterial pressure and the heart rate increased by more than 30 % from baseline. The depth of anaesthesia was adjusted to maintain a bispectral index (BIS) of 40–60. Invasive haemodynamic monitoring was used. Serum levels of IL-6, IL-8 and IL-10 were measured before surgery and anaesthesia, during tumour removal, at the end of surgery, and at 24 and 48 h after surgery. Postoperative complications (pain, vomiting, changes in blood pressure, infection and pulmonary, cardiovascular and neurological events) were monitored during the first 15 days after surgery.

Results

Compared with patients anaesthetised with sevoflurane, patients who received propofol had higher levels of IL-10 (p = 0.0001) and lower IL-6/IL-10 concentration ratio during and at the end of surgery (p = 0.0001). Both groups showed only a minor response of IL- 8 during and at the end of the surgery (p = 0.57).

Conclusions

Patients who received propofol had higher levels of IL-10 during surgery. Neither sevoflurane nor propofol had any significant impact on the occurrence of postoperative complications. Our findings should incite future studies to prove a potential medically important anti-inflammatory role of propofol in neuroanaesthesia.

Clinical trial registration

Identified as NCT02229201 at http://ift.tt/PmpYKN

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The prevalence and predictive value of the SLC30A8 R325W polymorphism and zinc transporter 8 autoantibodies in the development of GDM and postpartum type 1 diabetes

Abstract

The objectives were to evaluate possible associations between the SLC30A8 R325W polymorphism and gestational diabetes mellitus (GDM) as well as postpartum development of type 2 diabetes. Furthermore, we wanted to confirm the prevalence of zinc transporter 8 autoantibodies (ZnT8A), as previously reported, in a larger population and study its predictive value in relation to other β cell specific autoantibodies in postpartum development of type 1 diabetes. Women diagnosed with GDM (n = 776) and women without diabetes (n = 511) were included in the study. Autoantibodies were analyzed in all women using enzyme-linked immunosorbent assay. DNA was extracted when possible from women with GDM (n = 536) and all of the controls. R325W was detected through polymerase chain reaction and specific restriction digestion. The R325W C-allele were more frequent in women with GDM compared to in controls (OR 1.47, 95 % CI 1.16–1.88, p = 0.0018) but not significantly increased in women with GDM and postpartum development of type 2 diabetes. Autoantibodies were found in 6.8 % (53/776) of the women with GDM and approximately 3.2 % (25/776) were ZnT8A positive. Approximately 19 % (10/53) of the autoantibody positive women with GDM developed postpartum type 1 diabetes. In conclusion, this is the first study to report a significant association between the R325W C-allele and increased risk of developing GDM. All of the autoantibody positive women with GDM who developed postpartum type 1 diabetes were positive for autoantibodies against glutamic acid decarboxylase (GADA). Thus ZnT8A did not have any additional predictive value in postpartum development of type 1 diabetes.

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Does mandibular osteotomy affect gonial angle in patients with class III deformity? Vertical ramus osteotomy versus sagittal split osteotomy

Publication date: Available online 22 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): R. Tabrizi, H. Pakshir, H. Behnia, S. Akhlaghi, N. Shahsavari
The mandibular angle represents an important part of facial aesthetics. Mandibular osteotomy can affect the gonial angle. The aim of this study was to compare the effects of sagittal split osteotomy (SSO) and intraoral vertical ramus osteotomy (IVRO) on the gonial angle. This retrospective cohort study assessed subjects with mandibular prognathism who underwent SSO (group 1) or IVRO (group 2). Lateral cephalograms obtained before and 1 year after the osteotomies were analyzed. In this study, age, sex, the change in occlusal plane (OP) and mandibular plane (MP) angles, and the amount of mandibular setback were considered as variable factors, while the type of surgery (SSO or IVRO) was considered the predictive factor. Fifty-six subjects were studied: 26 in group 1 and 30 in group 2. The changes in MP angle and OP angle were not significantly different between the groups (P>0.05). The change in gonial angle was 6.07±4.46° in group 1 and 7.33±5.73° in group 2; assessment of the data did not demonstrate a significant difference between the two groups studied (P=0.53). Mandibular osteotomy (SSO or IVRO) may change the gonial angle, but a significant difference between SSO and IVRO was not detected.

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Pancreaticobiliary maljunction and choledochal cysts: from embryogenesis to therapeutics aspects

Abstract

Pancreaticobiliary maljunction (PBM) and choledochal cysts (CC) are rare and little-known diseases. Several definitions have been proposed for the PBM, but the most widely accepted is an excessive length of the common pancreaticobiliary duct due to the abnormal convergence of the pancreatic and biliary ducts out of the duodenal wall. This anomaly, thought to develop during embryogenesis, is associated with a loss of regulation of the Oddi's sphincter leading to a pancreaticobiliary or biliopancreatic backflow. This reflux could be responsible, or associated with cystic dilatation of the bile ducts and biliary tract cancers, to various biliary or pancreatic events such as cholangitis or pancreatitis. For the diagnosis of PBM, magnetic resonance cholangiopancreatography has now become the gold standard as a noninvasive imaging tool. However, the main risk of PBM is the development of bile duct cancer, most often on a distended area. PBM without CC increase the occurrence of gallbladder cancer and require a preventive cholecystectomy. Surgical treatment of PBM with concomitant CC is more complex and depends on localization of the dilatation(s) as reported in the Todani's classification. This review describes the pathogenesis, embryogenesis, clinical features, investigation and management of PBM and CC.

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Perforator anatomy of the radial forearm free flap versus the ulnar forearm free flap for head and neck reconstruction

Publication date: Available online 21 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): D.D. Hekner, T.A.P. Roeling, E.M. Van Cann
The aim of this study was to investigate the vascular anatomy of the distal forearm in order to optimize the choice between the radial forearm free flap and the ulnar forearm free flap and to select the best site to harvest the flap. The radial and ulnar arteries of seven fresh cadavers were injected with epoxy resin (Araldite) and the perforating arteries were dissected. The number of clinically relevant perforators from the radial and ulnar arteries was not significantly different in the distal forearm. Most perforators were located in the proximal half of the distal one third, making this part probably the safest location for flap harvest. Close to the wrist, i.e. most distally, there were more perforators on the ulnar side than on the radial side. The ulnar artery stained 77% of the skin surface area of the forearm, showing the ulnar forearm free flap to be more suitable than the radial forearm free flap for the restoration of large defects.

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The promising alliance of anti-cancer electrochemotherapy with immunotherapy

Abstract

Anti-tumor electrochemotherapy, which consists in increasing anti-cancer drug uptake by means of electroporation, is now implanted in about 140 cancer treatment centers in Europe. Its use is supported by the English National Institute for Health and Care Excellence for the palliative treatment of skin metastases, and about 13,000 cancer patients were treated by this technology by the end of 2015. Efforts are now focused on turning this local anti-tumor treatment into a systemic one. Electrogenetherapy, that is the electroporation-mediated transfer of therapeutic genes, is currently under clinical evaluation and has brought excitement to enlarge the anti-cancer armamentarium. Among the promising electrogenetherapy strategies, DNA vaccination and cytokine-based immunotherapy aim at stimulating anti-tumor immunity. We review here the interests and state of development of both electrochemotherapy and electrogenetherapy. We then emphasize the potent beneficial outcome of the combination of electrochemotherapy with immunotherapy, such as immune checkpoint inhibitors or strategies based on electrogenetherapy, to simultaneously achieve excellent local debulking anti-tumor responses and systemic anti-metastatic effects.

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Two cases of gallbladder metastasis from renal cell carcinoma and review of literature

Renal cell carcinoma accounts for 90 % of renal neoplasms and metastatic disease is common. One third of newly diagnosed cases will have synchronous metastases at diagnosis and further 25–50 % will develop met…

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Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report

The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemothe…

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Erratum to: Post-herpetic Neuralgia: a Review

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The genetic diversity of triticale genotypes involved in Polish breeding programs

Genetic diversity analysis of triticale populations is useful for breeding programs, as it helps to select appropriate genetic material for classifying the parental lines, heterotic groups and predicting hybri…

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Retinal artery occlusion by left atrial myxoma misdiagnosed as thrombus

Left atrial mass has been known to have a benign course.

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Does mandibular osteotomy affect gonial angle in patients with class III deformity? Vertical ramus osteotomy versus sagittal split osteotomy

Publication date: Available online 22 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): R. Tabrizi, H. Pakshir, H. Behnia, S. Akhlaghi, N. Shahsavari
The mandibular angle represents an important part of facial aesthetics. Mandibular osteotomy can affect the gonial angle. The aim of this study was to compare the effects of sagittal split osteotomy (SSO) and intraoral vertical ramus osteotomy (IVRO) on the gonial angle. This retrospective cohort study assessed subjects with mandibular prognathism who underwent SSO (group 1) or IVRO (group 2). Lateral cephalograms obtained before and 1 year after the osteotomies were analyzed. In this study, age, sex, the change in occlusal plane (OP) and mandibular plane (MP) angles, and the amount of mandibular setback were considered as variable factors, while the type of surgery (SSO or IVRO) was considered the predictive factor. Fifty-six subjects were studied: 26 in group 1 and 30 in group 2. The changes in MP angle and OP angle were not significantly different between the groups (P>0.05). The change in gonial angle was 6.07±4.46° in group 1 and 7.33±5.73° in group 2; assessment of the data did not demonstrate a significant difference between the two groups studied (P=0.53). Mandibular osteotomy (SSO or IVRO) may change the gonial angle, but a significant difference between SSO and IVRO was not detected.

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Perforator anatomy of the radial forearm free flap versus the ulnar forearm free flap for head and neck reconstruction

Publication date: Available online 21 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): D.D. Hekner, T.A.P. Roeling, E.M. Van Cann
The aim of this study was to investigate the vascular anatomy of the distal forearm in order to optimize the choice between the radial forearm free flap and the ulnar forearm free flap and to select the best site to harvest the flap. The radial and ulnar arteries of seven fresh cadavers were injected with epoxy resin (Araldite) and the perforating arteries were dissected. The number of clinically relevant perforators from the radial and ulnar arteries was not significantly different in the distal forearm. Most perforators were located in the proximal half of the distal one third, making this part probably the safest location for flap harvest. Close to the wrist, i.e. most distally, there were more perforators on the ulnar side than on the radial side. The ulnar artery stained 77% of the skin surface area of the forearm, showing the ulnar forearm free flap to be more suitable than the radial forearm free flap for the restoration of large defects.

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Relationship between cytochrome P450 polymorphisms and prescribed medication in elderly haemodialysis patients

Elderly patients on haemodialysis have a high prevalence of polypharmacy and are at risk of drug-related complications. More than 80 % of all prescribed drugs are metabolized by the cytochrome P450 (CYP) enzym…

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Transvenous extraction of pacemaker and implantable cardioverter defibrillator leads using Evolution® mechan ical dilator sheath: a single center confirmatory experience

In recent years there has been an increase in clinical situations requiring lead extraction procedures of implanted cardiac devices. In our clinic, extraction procedures are performed with Evolution® mechanica…

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Supratentorial subdural hematoma following microvascular decompression: a report of four cases

Microvascular decompression has become an accepted surgical technique for the treatment of trigeminal neuralgia, hemifacial spasm, and other cranial nerve rhizopathies. However, critical complications still ex…

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MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

Abstract

Glioma is a severe and highly lethal brain cancer, a malignancy largely stemming from growing in a relatively restrained area of the brain. Hence, the understanding of the molecular regulation of the growth of glioma is critical for improving its treatment. MicroRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. However, the molecular function and mechanisms of miR-508-5p in gliomagenesis are still unclear. The aim of this study was to investigate miR-508-5p expression in glioma and determine its effects on proliferation. miR-508-5p expression levels, both in glioma cell lines and in tissue, were significantly lower than in a normal human astrocyte cell line or adjacent tissues. Cell growth was analyzed using a MTT assay and over-expression of miR-508-5p was found to decrease glioma cell growth. Moreover, a bioinformatic analysis was performed, showing that glycoprotein non-metastatic melanoma B (GPNMB) was a direct target for miR-508-5p in glioma cells. Furthermore, in vivo treatment with miR-508-5p reduced GPNMB protein levels in the tumor. Additionally, overexpression of GPNMB without 3′-UTR partially reversed the cell growth arrest induced by miR-508-5p over-expression in glioma cells. In conclusion, these results indicate that increased expression of miR-508-5p might be related to glioma progression, indicating a potential role of miR-508-5p for clinical therapy.

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Perforator anatomy of the radial forearm free flap versus the ulnar forearm free flap for head and neck reconstruction

Publication date: Available online 21 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): D.D. Hekner, T.A.P. Roeling, E.M. Van Cann
The aim of this study was to investigate the vascular anatomy of the distal forearm in order to optimize the choice between the radial forearm free flap and the ulnar forearm free flap and to select the best site to harvest the flap. The radial and ulnar arteries of seven fresh cadavers were injected with epoxy resin (Araldite) and the perforating arteries were dissected. The number of clinically relevant perforators from the radial and ulnar arteries was not significantly different in the distal forearm. Most perforators were located in the proximal half of the distal one third, making this part probably the safest location for flap harvest. Close to the wrist, i.e. most distally, there were more perforators on the ulnar side than on the radial side. The ulnar artery stained 77% of the skin surface area of the forearm, showing the ulnar forearm free flap to be more suitable than the radial forearm free flap for the restoration of large defects.

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Effect of propofol and sevoflurane on the inflammatory response of patients undergoing craniotomy

Abstract

Background

The purpose of this randomised, single-centre study was to prospectively investigate the impact of anaesthetic techniques for craniotomy on the release of cytokines IL-6, IL-8, IL-10, and to determine whether intravenous anaesthesia compared to inhalational anaesthesia attenuates the inflammatory response.

Methods

The study enroled 40 patients undergoing craniotomy, allocated into two equal groups to receive either sevoflurane (n = 20) or propofol (n = 20) in conjunction with remifentanil and rocuronium. The lungs were ventilated mechanically to maintain normocapnia. Remifentanil infusion was adjusted according to the degree of surgical manipulation and increased when mean arterial pressure and the heart rate increased by more than 30 % from baseline. The depth of anaesthesia was adjusted to maintain a bispectral index (BIS) of 40–60. Invasive haemodynamic monitoring was used. Serum levels of IL-6, IL-8 and IL-10 were measured before surgery and anaesthesia, during tumour removal, at the end of surgery, and at 24 and 48 h after surgery. Postoperative complications (pain, vomiting, changes in blood pressure, infection and pulmonary, cardiovascular and neurological events) were monitored during the first 15 days after surgery.

Results

Compared with patients anaesthetised with sevoflurane, patients who received propofol had higher levels of IL-10 (p = 0.0001) and lower IL-6/IL-10 concentration ratio during and at the end of surgery (p = 0.0001). Both groups showed only a minor response of IL- 8 during and at the end of the surgery (p = 0.57).

Conclusions

Patients who received propofol had higher levels of IL-10 during surgery. Neither sevoflurane nor propofol had any significant impact on the occurrence of postoperative complications. Our findings should incite future studies to prove a potential medically important anti-inflammatory role of propofol in neuroanaesthesia.

Clinical trial registration

Identified as NCT02229201 at http://ift.tt/PmpYKN

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The prevalence and predictive value of the SLC30A8 R325W polymorphism and zinc transporter 8 autoantibodies in the development of GDM and postpartum type 1 diabetes

Abstract

The objectives were to evaluate possible associations between the SLC30A8 R325W polymorphism and gestational diabetes mellitus (GDM) as well as postpartum development of type 2 diabetes. Furthermore, we wanted to confirm the prevalence of zinc transporter 8 autoantibodies (ZnT8A), as previously reported, in a larger population and study its predictive value in relation to other β cell specific autoantibodies in postpartum development of type 1 diabetes. Women diagnosed with GDM (n = 776) and women without diabetes (n = 511) were included in the study. Autoantibodies were analyzed in all women using enzyme-linked immunosorbent assay. DNA was extracted when possible from women with GDM (n = 536) and all of the controls. R325W was detected through polymerase chain reaction and specific restriction digestion. The R325W C-allele were more frequent in women with GDM compared to in controls (OR 1.47, 95 % CI 1.16–1.88, p = 0.0018) but not significantly increased in women with GDM and postpartum development of type 2 diabetes. Autoantibodies were found in 6.8 % (53/776) of the women with GDM and approximately 3.2 % (25/776) were ZnT8A positive. Approximately 19 % (10/53) of the autoantibody positive women with GDM developed postpartum type 1 diabetes. In conclusion, this is the first study to report a significant association between the R325W C-allele and increased risk of developing GDM. All of the autoantibody positive women with GDM who developed postpartum type 1 diabetes were positive for autoantibodies against glutamic acid decarboxylase (GADA). Thus ZnT8A did not have any additional predictive value in postpartum development of type 1 diabetes.

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Does mandibular osteotomy affect gonial angle in patients with class III deformity? Vertical ramus osteotomy versus sagittal split osteotomy

Publication date: Available online 22 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): R. Tabrizi, H. Pakshir, H. Behnia, S. Akhlaghi, N. Shahsavari
The mandibular angle represents an important part of facial aesthetics. Mandibular osteotomy can affect the gonial angle. The aim of this study was to compare the effects of sagittal split osteotomy (SSO) and intraoral vertical ramus osteotomy (IVRO) on the gonial angle. This retrospective cohort study assessed subjects with mandibular prognathism who underwent SSO (group 1) or IVRO (group 2). Lateral cephalograms obtained before and 1 year after the osteotomies were analyzed. In this study, age, sex, the change in occlusal plane (OP) and mandibular plane (MP) angles, and the amount of mandibular setback were considered as variable factors, while the type of surgery (SSO or IVRO) was considered the predictive factor. Fifty-six subjects were studied: 26 in group 1 and 30 in group 2. The changes in MP angle and OP angle were not significantly different between the groups (P>0.05). The change in gonial angle was 6.07±4.46° in group 1 and 7.33±5.73° in group 2; assessment of the data did not demonstrate a significant difference between the two groups studied (P=0.53). Mandibular osteotomy (SSO or IVRO) may change the gonial angle, but a significant difference between SSO and IVRO was not detected.

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Pancreaticobiliary maljunction and choledochal cysts: from embryogenesis to therapeutics aspects

Abstract

Pancreaticobiliary maljunction (PBM) and choledochal cysts (CC) are rare and little-known diseases. Several definitions have been proposed for the PBM, but the most widely accepted is an excessive length of the common pancreaticobiliary duct due to the abnormal convergence of the pancreatic and biliary ducts out of the duodenal wall. This anomaly, thought to develop during embryogenesis, is associated with a loss of regulation of the Oddi's sphincter leading to a pancreaticobiliary or biliopancreatic backflow. This reflux could be responsible, or associated with cystic dilatation of the bile ducts and biliary tract cancers, to various biliary or pancreatic events such as cholangitis or pancreatitis. For the diagnosis of PBM, magnetic resonance cholangiopancreatography has now become the gold standard as a noninvasive imaging tool. However, the main risk of PBM is the development of bile duct cancer, most often on a distended area. PBM without CC increase the occurrence of gallbladder cancer and require a preventive cholecystectomy. Surgical treatment of PBM with concomitant CC is more complex and depends on localization of the dilatation(s) as reported in the Todani's classification. This review describes the pathogenesis, embryogenesis, clinical features, investigation and management of PBM and CC.

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Perforator anatomy of the radial forearm free flap versus the ulnar forearm free flap for head and neck reconstruction

Publication date: Available online 21 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): D.D. Hekner, T.A.P. Roeling, E.M. Van Cann
The aim of this study was to investigate the vascular anatomy of the distal forearm in order to optimize the choice between the radial forearm free flap and the ulnar forearm free flap and to select the best site to harvest the flap. The radial and ulnar arteries of seven fresh cadavers were injected with epoxy resin (Araldite) and the perforating arteries were dissected. The number of clinically relevant perforators from the radial and ulnar arteries was not significantly different in the distal forearm. Most perforators were located in the proximal half of the distal one third, making this part probably the safest location for flap harvest. Close to the wrist, i.e. most distally, there were more perforators on the ulnar side than on the radial side. The ulnar artery stained 77% of the skin surface area of the forearm, showing the ulnar forearm free flap to be more suitable than the radial forearm free flap for the restoration of large defects.

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The promising alliance of anti-cancer electrochemotherapy with immunotherapy

Abstract

Anti-tumor electrochemotherapy, which consists in increasing anti-cancer drug uptake by means of electroporation, is now implanted in about 140 cancer treatment centers in Europe. Its use is supported by the English National Institute for Health and Care Excellence for the palliative treatment of skin metastases, and about 13,000 cancer patients were treated by this technology by the end of 2015. Efforts are now focused on turning this local anti-tumor treatment into a systemic one. Electrogenetherapy, that is the electroporation-mediated transfer of therapeutic genes, is currently under clinical evaluation and has brought excitement to enlarge the anti-cancer armamentarium. Among the promising electrogenetherapy strategies, DNA vaccination and cytokine-based immunotherapy aim at stimulating anti-tumor immunity. We review here the interests and state of development of both electrochemotherapy and electrogenetherapy. We then emphasize the potent beneficial outcome of the combination of electrochemotherapy with immunotherapy, such as immune checkpoint inhibitors or strategies based on electrogenetherapy, to simultaneously achieve excellent local debulking anti-tumor responses and systemic anti-metastatic effects.

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Two cases of gallbladder metastasis from renal cell carcinoma and review of literature

Renal cell carcinoma accounts for 90 % of renal neoplasms and metastatic disease is common. One third of newly diagnosed cases will have synchronous metastases at diagnosis and further 25–50 % will develop met…

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Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report

The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemothe…

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Erratum to: Post-herpetic Neuralgia: a Review

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The genetic diversity of triticale genotypes involved in Polish breeding programs

Genetic diversity analysis of triticale populations is useful for breeding programs, as it helps to select appropriate genetic material for classifying the parental lines, heterotic groups and predicting hybri…

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Retinal artery occlusion by left atrial myxoma misdiagnosed as thrombus

Left atrial mass has been known to have a benign course.

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Relationship between cytochrome P450 polymorphisms and prescribed medication in elderly haemodialysis patients

Elderly patients on haemodialysis have a high prevalence of polypharmacy and are at risk of drug-related complications. More than 80 % of all prescribed drugs are metabolized by the cytochrome P450 (CYP) enzym…

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Transvenous extraction of pacemaker and implantable cardioverter defibrillator leads using Evolution® mechan ical dilator sheath: a single center confirmatory experience

In recent years there has been an increase in clinical situations requiring lead extraction procedures of implanted cardiac devices. In our clinic, extraction procedures are performed with Evolution® mechanica…

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Supratentorial subdural hematoma following microvascular decompression: a report of four cases

Microvascular decompression has become an accepted surgical technique for the treatment of trigeminal neuralgia, hemifacial spasm, and other cranial nerve rhizopathies. However, critical complications still ex…

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MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

Abstract

Glioma is a severe and highly lethal brain cancer, a malignancy largely stemming from growing in a relatively restrained area of the brain. Hence, the understanding of the molecular regulation of the growth of glioma is critical for improving its treatment. MicroRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. However, the molecular function and mechanisms of miR-508-5p in gliomagenesis are still unclear. The aim of this study was to investigate miR-508-5p expression in glioma and determine its effects on proliferation. miR-508-5p expression levels, both in glioma cell lines and in tissue, were significantly lower than in a normal human astrocyte cell line or adjacent tissues. Cell growth was analyzed using a MTT assay and over-expression of miR-508-5p was found to decrease glioma cell growth. Moreover, a bioinformatic analysis was performed, showing that glycoprotein non-metastatic melanoma B (GPNMB) was a direct target for miR-508-5p in glioma cells. Furthermore, in vivo treatment with miR-508-5p reduced GPNMB protein levels in the tumor. Additionally, overexpression of GPNMB without 3′-UTR partially reversed the cell growth arrest induced by miR-508-5p over-expression in glioma cells. In conclusion, these results indicate that increased expression of miR-508-5p might be related to glioma progression, indicating a potential role of miR-508-5p for clinical therapy.

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Nitrosative Stress in the Nervous System: Guidelines for Designing Experimental Strategies to Study Protein S-Nitrosylation

Abstract

Reactive nitrogen species, such as nitric oxide (NO), exert their biological activity in large part through post-translational modification of cysteine residues, forming S-nitrosothiols. This chemical reaction proceeds via a process that we and our colleagues have termed protein S-nitrosylation. Under conditions of normal NO production, S-nitrosylation regulates the activity of many normal proteins. However, in degenerative conditions characterized by nitrosative stress, increased levels of NO lead to aberrant S-nitrosylation that contributes to the pathology of the disease. Thus, S-nitrosylation has been implicated in a wide range of cellular mechanisms, including mitochondrial function, proteostasis, transcriptional regulation, synaptic activity, and cell survival. In recent years, the research area of protein S-nitrosylation has become prominent due to improvements in the detection systems as well as the demonstration that protein S-nitrosylation plays a critical role in the pathogenesis of neurodegenerative and other neurological disorders. To further promote our understanding of how protein S-nitrosylation affects cellular systems, guidelines for the design and conduct of research on S-nitrosylated (or SNO-)proteins would be highly desirable, especially for those newly entering the field. In this review article, we provide a strategic overview of designing experimental approaches to study protein S-nitrosylation. We specifically focus on methods that can provide critical data to demonstrate that an S-nitrosylated protein plays a (patho-)physiologically-relevant role in a biological process. Hence, the implementation of the approaches described herein will contribute to further advancement of the study of S-nitrosylated proteins, not only in neuroscience but also in other research fields.

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Does mandibular osteotomy affect gonial angle in patients with class III deformity? Vertical ramus osteotomy versus sagittal split osteotomy

Publication date: Available online 22 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): R. Tabrizi, H. Pakshir, H. Behnia, S. Akhlaghi, N. Shahsavari
The mandibular angle represents an important part of facial aesthetics. Mandibular osteotomy can affect the gonial angle. The aim of this study was to compare the effects of sagittal split osteotomy (SSO) and intraoral vertical ramus osteotomy (IVRO) on the gonial angle. This retrospective cohort study assessed subjects with mandibular prognathism who underwent SSO (group 1) or IVRO (group 2). Lateral cephalograms obtained before and 1 year after the osteotomies were analyzed. In this study, age, sex, the change in occlusal plane (OP) and mandibular plane (MP) angles, and the amount of mandibular setback were considered as variable factors, while the type of surgery (SSO or IVRO) was considered the predictive factor. Fifty-six subjects were studied: 26 in group 1 and 30 in group 2. The changes in MP angle and OP angle were not significantly different between the groups (P>0.05). The change in gonial angle was 6.07±4.46° in group 1 and 7.33±5.73° in group 2; assessment of the data did not demonstrate a significant difference between the two groups studied (P=0.53). Mandibular osteotomy (SSO or IVRO) may change the gonial angle, but a significant difference between SSO and IVRO was not detected.

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Perforator anatomy of the radial forearm free flap versus the ulnar forearm free flap for head and neck reconstruction

Publication date: Available online 21 March 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): D.D. Hekner, T.A.P. Roeling, E.M. Van Cann
The aim of this study was to investigate the vascular anatomy of the distal forearm in order to optimize the choice between the radial forearm free flap and the ulnar forearm free flap and to select the best site to harvest the flap. The radial and ulnar arteries of seven fresh cadavers were injected with epoxy resin (Araldite) and the perforating arteries were dissected. The number of clinically relevant perforators from the radial and ulnar arteries was not significantly different in the distal forearm. Most perforators were located in the proximal half of the distal one third, making this part probably the safest location for flap harvest. Close to the wrist, i.e. most distally, there were more perforators on the ulnar side than on the radial side. The ulnar artery stained 77% of the skin surface area of the forearm, showing the ulnar forearm free flap to be more suitable than the radial forearm free flap for the restoration of large defects.

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Effect of propofol and sevoflurane on the inflammatory response of patients undergoing craniotomy

Abstract

Background

The purpose of this randomised, single-centre study was to prospectively investigate the impact of anaesthetic techniques for craniotomy on the release of cytokines IL-6, IL-8, IL-10, and to determine whether intravenous anaesthesia compared to inhalational anaesthesia attenuates the inflammatory response.

Methods

The study enroled 40 patients undergoing craniotomy, allocated into two equal groups to receive either sevoflurane (n = 20) or propofol (n = 20) in conjunction with remifentanil and rocuronium. The lungs were ventilated mechanically to maintain normocapnia. Remifentanil infusion was adjusted according to the degree of surgical manipulation and increased when mean arterial pressure and the heart rate increased by more than 30 % from baseline. The depth of anaesthesia was adjusted to maintain a bispectral index (BIS) of 40–60. Invasive haemodynamic monitoring was used. Serum levels of IL-6, IL-8 and IL-10 were measured before surgery and anaesthesia, during tumour removal, at the end of surgery, and at 24 and 48 h after surgery. Postoperative complications (pain, vomiting, changes in blood pressure, infection and pulmonary, cardiovascular and neurological events) were monitored during the first 15 days after surgery.

Results

Compared with patients anaesthetised with sevoflurane, patients who received propofol had higher levels of IL-10 (p = 0.0001) and lower IL-6/IL-10 concentration ratio during and at the end of surgery (p = 0.0001). Both groups showed only a minor response of IL- 8 during and at the end of the surgery (p = 0.57).

Conclusions

Patients who received propofol had higher levels of IL-10 during surgery. Neither sevoflurane nor propofol had any significant impact on the occurrence of postoperative complications. Our findings should incite future studies to prove a potential medically important anti-inflammatory role of propofol in neuroanaesthesia.

Clinical trial registration

Identified as NCT02229201 at http://ift.tt/PmpYKN

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Male patients require higher optimal effect-site concentrations of propofol during i-gel insertion with dexmedetomidine 0.5 μg/kg

Abstract

Background

The pharmacokinetics and pharmacodynamics of an anesthetic drug may be influenced by gender. The purpose of this study was to compare effect-site half maximal effective concentrations (EC50) of propofol in male and female patients during i-gel insertion with dexmedetomidine 0.5 μg/kg without muscle relaxants.

Methods

Forty patients, aged 20–46 years of ASA physical status I or II, were allocated to one of two groups by gender (20 patients per group). After the infusion of dexmedetomidine 0.5 μg/kg over 2 min, anesthesia was induced with a pre-determined effect-site concentration of propofol by target controlled infusion. Effect-site EC50 values of propofol for successful i-gel insertion were determined using the modified Dixon's up-and-down method.

Results

Mean effect-site EC50 ± SD of propofol for successful i-gel insertion was significantly higher for men than women (5.46 ± 0.26 μg/ml vs. 3.82 ± 0.34 μg/ml, p < 0.01). The EC50 of propofol in men was approximately 40 % higher than in women. Using isotonic regression with a bootstrapping approach, the estimated EC50 (95 % confidence interval) of propofol was also higher in men [5.32 (4.45–6.20) μg/ml vs. 3.75 (3.05–4.43) μg/ml]. The estimated EC95 (95 % confidence interval) of propofol in men and women were 5.93 (4.72–6.88) μg/ml and 4.52 (3.02–5.70) μg/ml, respectively.

Conclusions

During i-gel insertion with dexmedetomidine 0.5 μg/kg without muscle relaxant, male patients had higher effect-site EC50 for propofol using Schnider's model. Based on the results of this study, patient gender should be considered when determining the optimal dose of propofol during supraglottic airway insertion.

Trial registration

ClinicalTrials.gov identifier: NCT02268656. Registered August 26, 2014.

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Perceptions about the relative importance of patient care-related topics: a single institutional survey of its anesthesiologists, nurse anesthetists, and surgeons

Abstract

Background

Persistently variable success has been experienced in locally translating even well-grounded national clinical practice guidelines, including in the perioperative setting. We have sought greater applicability and acceptance of clinical practice guidelines and protocols with our novel Perioperative Risk Optimization and Management Planning Tool (PROMPT™). This study was undertaken to survey our institutional perioperative clinicians regarding (a) their qualitative recommendations for (b) their quantitative perceptions of the relative importance of a series of clinical issues and patient medical conditions as potential topics for creating a PROMPT™.

Methods

We applied a mixed methods research design that involved collecting, analyzing, and "mixing" both qualitative and quantitative methods and data in a single study to answer a research question. Survey One was qualitative in nature and asked the study participants to list as free text up to 12 patient medical conditions or clinical issues that they perceived to be high priority topics for development of a PROMPT™. Survey Two was quantitative in nature and asked the study participants to rate each of these 57 specific, pre-selected clinical issues and patient medical conditions on an 11-point Likert scale of perceived importance as a potential topic for a PROMPT™. The two electronic, online surveys were completed by participants who were recruited from the faculty in our Department of Anesthesiology and Perioperative Medicine and Department of Surgery, and the cohort of hospital-employed certified registered nurse anesthetists.

Results

A total of 57 possible topics for a PROMPT™ was created and prioritized by our stakeholders. A strong correlation (r = 0.82, 95 % CI: 0.71, 0.89, P < 0.001) was observed between the quantitative clinician survey rating scores reported by the anesthesiologists/certified registered nurse anesthetists versus the surgeons. The quantitative survey displayed strong inter-rater reliability (ICC = 0.92, P < 0.001).

Conclusions

Our qualitative clinician stakeholder survey generated a comprehensive roster of clinical issues and patient medical conditions. Our subsequent quantitative clinician stakeholder survey indicated that there is generally strong agreement among anesthesiologists/certified registered nurse anesthetists and surgeons about the relative importance of these clinical issues and patient medical conditions as potential topics for perioperative optimization and risk management.

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The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells

Summary

Inhibitors of kinesin spindle protein Eg5 are characterized by pronounced antitumor activity. Our group has recently synthesized and screened a library of 1,3,4-thiadiazoline analogues with the pharmacophoric structure of K858, an Eg5 inhibitor. We herein report the effects of K858 on four different breast cancer cell lines: MCF7 (luminal A), BT474 (luminal B), SKBR3 (HER2 like) and MDA-MB231 (basal like). We demonstrated that K858 displayed anti-proliferative activity on every analyzed breast cancer cell line by inducing apoptosis. However, at the same time, we showed that K858 up-regulated survivin, an anti-apoptotic molecule. We then performed a negative regulation of survivin expression, with the utilization of wortmannin, an AKT inhibitor, and obtained a significant increase of K858-dependent apoptosis. These data demonstrate that K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis.

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Erratum to: Pharmacokinetic evaluation of nanoparticle albumin-bound paclitaxel delivered via hepatic arterial infusion in patients with predominantly hepatic metastases

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Early impact of the Patient Protection and Affordable Care Act on insurance among young adults with cancer: Analysis of the dependent insurance provision

BACKGROUND

The Patient Protection and Affordable Care Act (ACA) included provisions to extend dependent health care coverage up to the age of 26 years in 2010. The authors examined the early impact of the ACA (before the implementation of insurance exchanges in 2014) on insurance rates in young adults with cancer, a historically underinsured group.

METHODS

Using National Cancer Institute Surveillance, Epidemiology, and End Results data for 18 cancer registries, the authors examined insurance rates before (pre) (January 2007-September 2010) versus after (post) (October 2010-December 2012) dependent insurance provisions among young adults aged 18 to 29 years when diagnosed with cancer during 2007 through 2012. Using multivariate generalized mixed effect models, the authors conducted difference-in-differences analysis to examine changes in overall and Medicaid insurance after the ACA among young adults who were eligible (those aged 18-25 years) and ineligible (those aged 26-29 years) for policy changes.

RESULTS

Among 39,632 young adult cancer survivors, the authors found an increase in overall insurance rates in those aged 18 to 25 years after the dependent provisions (83.5% for pre-ACA vs 85.4% for post-ACA; P<.01), but not among individuals aged 26 to 29 years (83.4% for pre-ACA vs 82.9% for post-ACA; P = .38). After adjusting for patient sociodemographics and cancer characteristics, the authors found that those aged 18 to 25 years had a 3.1% increase in being insured compared with individuals aged 26 to 29 years (P<.01); however, there were no significant changes noted in Medicaid enrollment (P = .17).

CONCLUSIONS

The findings of the current study identify an increase in insurance rates for young adults aged 18 to 25 years compared with those aged 26 to 29 years (1.9% vs -0.5%) that was not due to increases in Medicaid enrollment, thereby demonstrating a positive impact of the ACA dependent care provisions on insurance rates in this population. Cancer 2016. © 2016 American Cancer Society.

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A phase II, open-label trial of bortezomib (VELCADE ® ) in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic non-small cell lung cancer

Abstract

Background

Bortezomib is a selective reversible proteasome inhibitor with proapoptotic effects. Preclinical and phase I clinical data suggest activity of bortezomib in NSCLC, either as monotherapy or in combination with chemotherapeutic agents including gemcitabine and cisplatin.

Methods

Chemotherapy-naïve patients with inoperable stage IIIB or IV NSCLC were administered bortezomib 1 mg/m2 i.v. on days 1 and 8, and starting on day 21 (cycle 2), bortezomib (days 1 and 8) in combination with gemcitabine 1000 mg/m2, (days 1 and 8), and cisplatin 70 mg/m2 (day 1) in cycles of 21 days. Up to 8 cycles of combination therapy could be administered; single-agent bortezomib was continued until disease progression or unacceptable toxicity.

Results

Fifty-three patients [median age 66 years; 79.2 % male; 96.2 % stage IV; performance status (ECOG) 0/1 73.6/26.4 %; adenocarcinoma 45.3 %, squamous cell carcinoma 41.5 %] were enrolled. All patients were evaluable for toxicity and 43 for efficacy. Grade 3–4 hematologic toxicity consisted of neutropenia (22.6 %) and thrombocytopenia (17 %). Grade 2–4 non-hematologic adverse events were fever (9.4 %), fatigue (20.8 %), infection (18.9 %), and dyspnea (15.1 %). There was no >grade 2 neurotoxicity. Febrile neutropenia occurred in two (1.9 %) patients, and there were three possibly treatment-related deaths (5.4 %). In the intention-to-treat population, the objective response rate was 17 % (95 % CI 6.9–27.1 %). No difference in response rate was observed for squamous versus other histology (18.2 vs. 16.1 %, p = 0.845). The median progression-free survival was 2.5 months, the median overall survival 10.6 months and the 1-year survival rate 38.1 %.

Conclusion

The incorporation of bortezomib into the gemcitabine/cisplatin regimen, in the dose and schedule used in this study, could not improve the efficacy of the chemotherapy regimen and has not to be further investigated.

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The IL-1 cytokine family and its role in inflammation and fibrosis in the lung

Abstract

The IL-1 cytokine family comprises 11 members (7 ligands with agonist activity, 3 receptor antagonists and 1 anti-inflammatory cytokine) and is recognised as a key mediator of inflammation and fibrosis in multiple tissues including the lung. IL-1 targeted therapies have been successfully employed to treat a range of inflammatory conditions such as rheumatoid arthritis and gouty arthritis. This review will introduce the members of the IL-1 cytokine family, briefly discuss the cellular origins and cellular targets and provide an overview of the role of these molecules in inflammation and fibrosis in the lung.

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Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia

Abstract

Accumulating evidence indicates that enhancer of zeste homolog 2 (EZH2) promotes the metastatic ability of solid tumors, but the role of EZH2 in extramedullary infiltration (EMI) in acute myeloid leukemia (AML) has not been thoroughly explored. In the present study, we investigated the possible association between EZH2 and EMI. We found that the messenger RNA (mRNA) and protein expression levels of EZH2 in AML patients were both significantly higher than in idiopathic thrombocytopenic purpura (ITP) patients. Furthermore, a positive correlation between EZH2 mRNA expression and percentage of peripheral blood blasts wa s found in AML patients (r = 0.404, p = 0.009). The migratory capacities of Kasumi-1 and HL-60, which both show a high level of EZH2 expression, were markedly higher than those of U937 and KG-1α. In contrast, silencing of EZH2 resulted in reduction in proliferation and migration ability and an increase in apoptosis. The latter observation was accompanied by reduced expression of associated proteins p-ERK, p-cmyc, and matrix metalloproteinase 2 (MMP-2) and an increase in epithelial cadherin (E-cadherin). These data suggest that higher expression of EZH2 may be associated with extramedullary infiltration in acute myeloid leukemia and affect pathogenesis via activation of the p-ERK/p-cmyc/MMP-2 and E-cadherin signaling pathways.

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Pearls & Oy-sters: Symptomatic innominate artery disease

A 64-year-old man presented to the emergency department with left-sided weakness and speech impairment upon awakening. He had a history of multiple myocardial infarctions and had undergone coronary angioplasty and coronary artery bypass graft surgery 1 year previously. He was a heavy smoker and had arterial hypertension. He was taking aspirin 100 mg QD, clopidogrel 75 mg QD, simvastatin 40 mg QD, and enalapril 5 mg BID.

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Hair dye use, regular exercise, and the risk and prognosis of prostate cancer: multicenter case–control and case-only studies

This study investigated the effects that hair dye use and regular exercise exert on the risk and prognosis of prostate cancer.

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Teaching NeuroImages: Severe vasospasm in traumatic brain injury

A 45-year-old man had a severe traumatic brain injury (TBI) with multicompartmental hemorrhages (figure 1). He was initially noted to be awake and following commands with his right side. Two weeks later, his examination deteriorated to coma with flaccid quadriplegia. Initial workup, including EEG, was unrevealing. MRI brain showed new multiterritorial infarcts (figure 1); a catheter-based angiogram confirmed severe vasospasm in several large vessels (figure 2).

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Metabolic changes associated with tumor metastasis, part 1: tumor pH, glycolysis and the pentose phosphate pathway

Abstract

Metabolic adaptations are intimately associated with changes in cell behavior. Cancers are characterized by a high metabolic plasticity resulting from mutations and the selection of metabolic phenotypes conferring growth and invasive advantages. While metabolic plasticity allows cancer cells to cope with various microenvironmental situations that can be encountered in a primary tumor, there is increasing evidence that metabolism is also a major driver of cancer metastasis. Rather than a general switch promoting metastasis as a whole, a succession of metabolic adaptations is more likely needed to promote different steps of the metastatic process. This review addresses the contribution of pH, glycolysis and the pentose phosphate pathway, and a companion paper summarizes current knowledge regarding the contribution of mitochondria, lipids and amino acid metabolism. Extracellular acidification, intracellular alkalinization, the glycolytic enzyme phosphoglucose isomerase acting as an autocrine cytokine, lactate and the pentose phosphate pathway are emerging as important factors controlling cancer metastasis.

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Adjuvant and Novel Treatment of Recurrent Respiratory Papillomatosis

Abstract

Recurrent respiratory papillomatosis (RRP) is a rare benign neoplasm of the respiratory tract caused by human papillomavirus types 6 and 11. Surgical removal of the papilloma by microdebridement or laser is the current standard of care, but in most cases the disease recurs and patients require repeated surgical intervention. Over time, repeated procedures can lead to complications such as significant vocal cord scarring and laryngeal stenosis. There is therefore an urgent need for adjuvant treatments or alternative therapies that can control the disease or prevent recurrence, but unfortunately there is currently no known universally effective adjuvant therapy. Challenges for evaluating the effectiveness of adjuvant treatment in RRP include variable success rates in patients, the highly unpredictable underlying disease process, and potential for side effects. The current adjuvant treatment and novel approaches for RRP are presented.

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Dengue virus infection in a French traveller to the hilly region of Nepal in 2015: a case report

Dengue viral infections are known to pose a significant risk during travel to tropical regions, but it is surprising to find dengue transmission in the hilly region of Nepal, which is over 1800mtr above sea le...

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Volume matters in the systemic treatment of metastatic pancreatic cancer: a population-based study in the Netherlands

Abstract

Purpose

In pancreatic surgery, a relation between surgical volume and postoperative mortality and overall survival (OS) has been recognized, with high-volume centers reporting significantly better survival rates. We aimed to explore the influence of hospital volume on administration of palliative chemotherapy and OS in the Netherlands.

Methods

Patients diagnosed between 2007 and 2011 with metastatic pancreatic cancer were identified in the Netherlands Cancer Registry. Three types of high-volume centers were defined: high-volume (1) incidence center, based on the number of patients diagnosed with metastatic pancreatic cancer, (2) treatment center based on number of patients with metastatic pancreatic cancer who started treatment with palliative chemotherapy and (3) surgical center based on the number of resections with curative intent for pancreatic cancer. Independent predictors of administration of palliative chemotherapy were evaluated by means of logistic regression analysis. The multivariable Cox proportional hazard model was used to assess the impact of being diagnosed or treated in high-volume centers on survival.

Results

A total of 5385 patients presented with metastatic pancreatic cancer of which 24 % received palliative chemotherapy. Being treated with chemotherapy in a high-volume chemotherapy treatment center was associated with improved survival (HR 0.76, 95 % CI 0.67–0.87). Also, in all patients with metastatic pancreatic cancer, being diagnosed in a high-volume surgical center was associated with improved survival (HR 0.74, 95 % CI 0.66–0.83).

Conclusions

Hospital volume of palliative chemotherapy for metastatic pancreatic cancer was associated with improved survival, demonstrating that a volume–outcome relationship, as described for pancreatic surgery, may also exist for pancreatic medical oncology.

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