Head and Neck Diseases by Alexandros G.Sfakianakis: 03/12/16

Σάββατο 12 Μαρτίου 2016

Genetic progression of malignant melanoma

Abstract

Malignant melanoma of the skin is the most aggressive human cancer given that a primary tumor a few millimeters in diameter frequently has full metastatic competence. In view of that, revealing the genetic background of this potential may also help to better understand tumor dissemination in general. Genomic analyses have established the molecular classification of melanoma based on the most frequent driver oncogenic mutations (BRAF, NRAS, KIT) and have also revealed a long list of rare events, including mutations and amplifications as well as genetic microheterogeneity. At the moment, it is unclear whether any of these rare events have role in the metastasis initiation process since the major drivers do not have such a role. During lymphatic and hematogenous dissemination, the clonal selection process is evidently reflected by differences in oncogenic drivers in the metastases versus the primary tumor. Clonal selection is also evident during lymphatic progression, though the genetic background of this immunoselection is less clear. Genomic analyses of metastases identified further genetic alterations, some of which may correspond to metastasis maintenance genes. The natural genetic progression of melanoma can be modified by targeted (BRAF or MEK inhibitor) or immunotherapies. Some of the rare events in primary tumors may result in primary resistance, while further new genetic lesions develop during the acquired resistance to both targeted and immunotherapies. Only a few genetic lesions of the primary tumor are constant during natural or therapy-modulated progression. EGFR4 and NMDAR2 mutations, MITF and MET amplifications and PTEN loss can be considered as metastasis drivers. Furthermore, BRAF and MITF amplifications as well as PTEN loss are also responsible for resistance to targeted therapies, whereas NRAS mutation is the only founder genetic lesion showing any association with sensitivity to immunotherapies. Unfortunately, there are hardly any data on the possible organ-specific metastatic drivers in melanoma. These observations suggest that clinical management of melanoma patients must rely on the genetic analysis of the metastatic lesions to be able to monitor progression-associated changes and to personalize therapies.

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miR clusters target cellular functional complexes by defining their degree of regulatory freedom

Abstract

Using the two paralog miR-23∼27∼24 clusters as an example and combining experimental and clinical data in a systematical approach to microRNA (miR) function and dysregulation, a complex picture of their roles in cancer is drawn. Various findings appear to be contradictory to a larger extent and cannot be fully explained by the classical regulatory network models and feedback loops that are mainly considered by one-to-one regulatory interactions of the involved molecules. Here, we propose an extended model of the regulatory role of miRs that, at least, supplements the usually considered single/oligo-target regulation of certain miRs. The cellular availability of the participating miR members in this model reflects an upper hierarchy level of intracellular and extracellular environmental influences, such as neighboring cells, soluble factors, hypoxia, chemotherapeutic drugs, and irradiation, among others. The novel model is based on the understanding of cellular functional complexes, such as for apoptosis, migration, and proliferation. These complexes consist of many regulatory components that can be targeted by miR cluster members to a different extent but may affect the functional complex in different ways. We propose that the final miR-related effect is a result of the possible degree of regulatory freedom provided by the miR effects on the whole functional complex structure. This degree of regulatory freedom defines to which extent the cellular functional complex can react in response to regulatory triggers, also understood as sensitization (more regulatory response options) or de-sensitization (less regulatory response options) of the system rather than single molecules.

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Personalized treatment of advanced non-small-cell lung cancer in routine clinical practice

Abstract

Personalized treatment of patients with advanced non-small-cell lung cancer based on clinical and molecular tumor features has entered clinical routine practice. The 2015 pathological classification of lung cancer mandates immunohistochemical and molecular analysis. Therapeutic strategies focused on inhibition of angiogenesis and growth factor receptor signaling. Inhibitors of angiogenesis and monoclonal antibodies directed against the epidermal growth factor receptor have shown efficacy in combination with chemotherapy. Mutations in the epidermal growth factor receptor and anaplastic lymphoma kinase have become clinically relevant therapeutic targets. Immune checkpoint inhibitors are also entering routine clinical practice. Identification of predictive biomarkers is essential and faces several challenges including tumor heterogeneity and dynamic changes of tumor features over time. Liquid biopsies may overcome some of these challenges in the future.

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Shear Wave Elastography and Cervical Lymph Nodes: Predicting Malignancy

Publication date: Available online 12 March 2016
Source:Ultrasound in Medicine & Biology
Author(s): Ghobad Azizi, James M. Keller, Michelle L. Mayo, Kelé Piper, David Puett, Karly M. Earp, Carl D. Malchoff
This prospective study evaluates the accuracy of virtual touch imaging quantification (VTIQ), a non-invasive shear wave elastography method for measuring cervical lymph nodes (LN) stiffness in differentiating benign from malignant LN. The study evaluated 270 LN in 236 patients with both conventional B-mode ultrasound and VTIQ shear wave elastography before fine-needle aspiration biopsy (FNAB). LN stiffness was measured as shear wave velocity (SWV) in m/s. Surgical resection was advised for FNAB results that were not clearly benign. Surgical pathology confirmed 54 malignant LN. The receiver operating curve (ROC) identified a single cut-off value of 2.93 m/s as the maximum SWV for predicting a malignant cervical LN. The sensitivity and specificity were 92.59% and 75.46%, respectively. Positive predictive value (PPV) was 48.54% and negative predictive value (NPV) was 97.60%. LN stiffness measured by VTIQ–generated shear wave elastography is an independent predictor of malignancy.

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Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models?

Abstract

In the era of modern radiation therapy, the compromise between the reductions in deterministic radiation-induced toxicities through highly conformal devices may be impacting the stochastic risk of second malignancies. We reviewed the clinical literature and evolving theoretical models evaluating the impact of intensity-modulated radiation therapy (IMRT) on the risk of second cancers, as a consequence of the increase in volumes of normal tissues receiving low doses. The risk increase (if any) is not as high as theoretical models have predicted in adults. Moreover, the increase in out-of-field radiation doses with IMRT could be counterbalanced by the decrease in volumes receiving high doses. Clinical studies with short follow-up have not corroborated the hypothesis that IMRT would drastically increase the incidence of second cancers. In children, the risk of radiation-induced carcinogenesis increases from low doses and consequently the relative risk of second cancers after IMRT could be higher than in adults, justifying current developments of proton therapy with priority given to this population. Although only longer follow-up will allow a true assessment of the real impact of these modern techniques on radiation-induced carcinogenesis, a comprehensive risk-adapted strategy will help minimize the probability of second cancers.

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Characterization of class II β chain major histocompatibility complex genes in a family of Hawaiian honeycreepers: ‘amakihi ( Hemignathus virens )

Abstract

Hawaiian honeycreepers (Drepanidinae) have evolved in the absence of mosquitoes for over five million years. Through human activity, mosquitoes were introduced to the Hawaiian archipelago less than 200 years ago. Mosquito-vectored diseases such as avian malaria caused by Plasmodium relictum and Avipoxviruses have greatly impacted these vulnerable species. Susceptibility to these diseases is variable among and within species. Due to their function in adaptive immunity, the role of major histocompatibility complex genes (Mhc) in disease susceptibility is under investigation. In this study, we evaluate gene organization and levels of diversity of Mhc class II β chain genes (exon 2) in a captive-reared family of Hawaii 'amakihi (Hemignathus virens). A total of 233 sequences (173 bp) were obtained by PCR+1 amplification and cloning, and 5720 sequences were generated by Roche 454 pyrosequencing. We report a total of 17 alleles originating from a minimum of 14 distinct loci. We detected three linkage groups that appear to represent three distinct haplotypes. Phylogenetic analysis revealed one variable cluster resembling classical Mhc sequences (DAB) and one highly conserved, low variability cluster resembling non-classical Mhc sequences (DBB). High net evolutionary divergence values between DAB and DBB resemble that seen between chicken BLB system and YLB system genes. High amino acid identity among non-classical alleles from 12 species of passerines (DBB) and four species of Galliformes (YLB) was found, suggesting that these non-classical passerine sequences may be related to the Galliforme YLB sequences.

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In Memoriam: Dr. William John Garrett, AM

Publication date: Available online 12 March 2016
Source:Ultrasound in Medicine & Biology
Author(s): George Kossoff

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Presenting hydrothorax predicts failure of needle aspiration in primary spontaneous pneumothorax

Publication date: Available online 11 March 2016
Source:The American Journal of Emergency Medicine
Author(s): Kwok Kei Wu, Chun Tat Lui, Chik Leung Ho, Kwok Leung Tsui, Hin Tat Fung
ObjectiveTo evaluate if existence of hydrothorax in initial chest X-ray predict treatment outcome in patients with primary spontaneous pneumothorax received needle thoracostomy.MethodsThis is a retrospective cohort study carried out from January 2011 to August 2014 in one public hospital in Hong Kong. All consecutive adult patients aged 18 years or above who attended the emergency department with the diagnosis of primary spontaneous pneumothorax with needle aspiration was performed as primary treatment were included. Age, smoking status, size of pneumothorax, previous history of pneumothorax, aspirated gas volume and presence of hydropneumothorax in initial X-ray were included in the analysis. The outcome was successful or failure of the needle aspiration. Logistic regression was used to identify the predicting factors of failure of needle aspiration.ResultThere were totally 127 patients included. 73 patients (57.5%) were successfully treated with no recurrence upon discharge. Among 54 failure cases, 13 patients (10.2%) failed immediately after procedure as evident by chest X-ray that require second treatment. 41 patients (32.3%) failed upon subsequent chest X-rays. Multivariate logistic regression showed factors independently associated with the failure of needle aspiration, which included hydropneumothorax in the initial X-ray (OR=4.47 [1.56 – 12.83], p=0.005), previous history of pneumothorax (OR=3.92 [1.57-9.79], p=0.003) and large size of pneumothorax defined as apex-to-cupola disease ≥ 5cm (OR=2.75 [1.21-6.26], p=0.016).ConclusionsHydropneumothorax, previous history of pneumothorax and large size were independent predictors of failure of needle aspiration in treatment of primary spontaneous pneumothorax.

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Do trauma patients with phencyclidine positive urine drug screens have increased morbidity or mortality?

Publication date: Available online 11 March 2016
Source:The American Journal of Emergency Medicine
Author(s): Ryan Gallagher, Jonathan Dangers, Stephen L. Thornton
BackgroundPhencyclidine (PCP) use is anecdotally associated with agitation and injury and is frequently tested for in the setting of trauma. We sought to determine characteristics of trauma patients with a PCP positive urine immunoassay drug screen (UDS) and if they had increased levels of care or mortality.MethodsA five year retrospective review of a level 1 trauma center's trauma registry identified patients with a PCP positive UDS. This group was then compared with two randomly selected control groups from the same trauma registry which were matched for age and sex but differed in that one had no sEtOH detected and a negative UDS (Drug Free group) while the other had sEtOH or an other-than-PCP positive UDS (Other Drugs group). Subgroup analysis was performed comparing PCP positive patients with undetectable sETOH to Other Drug patients with undetectable sEtOH.ResultsThe registry contained 7770 patients of which 156 met inclusion criteria. The mean age was 33.4 years (range 19-63) and 77% were male (n=121). When compared to the Other Drug group the PCP positive group had significantly lower ISS, rates of ICU admission, and sEtOH. No difference was seen in vital signs, mechanism of injury, ventilator days, ICU days, total hospital days, disposition, or mortality between the three groups. This remained true even when subgroups with negative sEToH were compared.ConclusionThis study suggests a PCP positive UDS in the setting of trauma is not associated with increased level of care, length of stay, or mortality.

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Gap Between Official Guidelines and Clinical Practice for the Treatment of Rheumatoid Arthritis in São Paulo, Brazil

Publication date: Available online 11 March 2016
Source:Clinical Therapeutics
Author(s): Iara Alves de Camargo, Bruna Cipriano Almeida Barros, Miriam Sanches do Nascimento Silveira, Claudia Garcia Serpa Osorio-de-Castro, Gordon Guyatt, Luciane Cruz Lopes
PurposeBiological agents used for the treatment of rheumatoid arthritis (RA) are associated with serious adverse events. Guidelines provide standards for the prescribing and monitoring of these drugs. In São Paulo, health litigation for access to medicines has fueled the demand for biological therapy. The extent to which biological agents are being appropriately prescribed and patients are being appropriately monitored is uncertain. Our goal was to determine whether RA clinical guidelines are being translated into clinical practice for patients receiving treatment as a result of lawsuits against the government.MethodsWe identified patients through records of the State Secretary of Health of São Paulo from 2003 to 2011. We consulted guidelines from 5 countries and chose those recommendations endorsed by all of the guidelines reviewed as standards. Pharmacy records provided data regarding biologic use. The guidelines recommended the use of biological agents only when patients had been receiving treatment with at least 1 disease-modifying antirheumatic drug (DMARD) and recommended annual monitoring of laboratory blood tests.FindingsOf the 238 patients identified in the database, 216 patients were interviewed, and 124 (57.4%) patients were still using biological agents at the time of the survey. Of the patients interviewed, 167 patients (77.3%) started biological treatment when using ≥2 DMARDs before, 22 patients (10.2%) were using 1 DMARD before, and 27 patients (12.5%) had never taken a DMARD. Of the 124 patients still taking biological drugs, 117 patients (94.3%) had visited a doctor at least once per year, but 28 patients (22.6%) did not undergo the recommended laboratory blood testing. Only 43 of the 124 patients (34.7%) still taking biological agents met the guideline criteria for both the use of previous agents and the appropriate monitoring.ImplicationsAn important gap between clinical practice and the national guidelines exists among treatments prescribed for plaintiffs obtaining medicines for RA in São Paulo. The results suggest the need for intervention by health authorities.

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Error Rates, Decisive Outcomes and Publication Bias with Several Inferential Methods

Abstract

Background

Statistical methods for inferring the true magnitude of an effect from a sample should have acceptable error rates when the true effect is trivial (type I rates) or substantial (type II rates).

Objective

The objective of this study was to quantify the error rates, rates of decisive (publishable) outcomes and publication bias of five inferential methods commonly used in sports medicine and science. The methods were conventional null-hypothesis significance testing [NHST] (significant and non-significant imply substantial and trivial true effects, respectively); conservative NHST (the observed magnitude is interpreted as the true magnitude only for significant effects); non-clinical magnitude-based inference [MBI] (the true magnitude is interpreted as the magnitude range of the 90 % confidence interval only for intervals not spanning substantial values of the opposite sign); clinical MBI (a possibly beneficial effect is recommended for implementation only if it is most unlikely to be harmful); and odds-ratio clinical MBI (implementation is also recommended when the odds of benefit outweigh the odds of harm, with an odds ratio >66).

Methods

Simulation was used to quantify standardized mean effects in 500,000 randomized, controlled trials each for true standardized magnitudes ranging from null through marginally moderate with three sample sizes: suboptimal (10 + 10), optimal for MBI (50 + 50) and optimal for NHST (144 + 144).

Results

Type I rates for non-clinical MBI were always lower than for NHST. When type I rates for clinical MBI were higher, most errors were debatable, given the probabilistic qualification of those inferences (unlikely or possibly beneficial). NHST often had unacceptable rates for either type II errors or decisive outcomes, and it had substantial publication bias with the smallest sample size, whereas MBI had no such problems.

Conclusion

MBI is a trustworthy, nuanced alternative to NHST, which it outperforms in terms of the sample size, error rates, decision rates and publication bias.

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Renal cell carcinoma: staging and surveillance

Abstract

Renal cell carcinoma is a common malignancy with many histologic subtypes. Appropriate treatment depends not only upon the specific subtype but also the size of the tumor and extent of spread at time of presentation. Approximately 5% of RCCs are part of a hereditary syndrome which must also be considered in the therapeutic decisions. Although some RCCs are detected with ultrasound, CT or MR is required for staging. CT is used most commonly as it is most readily available and relatively less expensive than MR imaging. The TNM classification of the American Joint Committee on Cancer has largely replaced the Robson classification. Early detection, accurate staging, and improved treatment options have resulted in improved 5-year survival of patients with renal carcinoma.

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Imaging wisely: patient safety in CT

Abstract

The past decade has seen a significant growth in diagnostic CT imaging as a direct result of the clinical value provided by CT imaging. At the same time, many new techniques and resources are now available to make CT imaging safe. This article presents the basics of CT dosimetry and their usage in clinical practices, methods to implement CT dose reduction, followed by a summary of legislation, and guidelines related to patient safety in diagnostic CT imaging. Also, CT radiation dose diagnostic reference levels from published regional and national surveys are reviewed and applied in a CT dose tracking and monitoring program.

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Abdominal radiology in the era of the Interventional Radiology/Diagnostic Radiology certificate

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Comparison of hepatocellular carcinoma conspicuity on hepatobiliary phase images with gadoxetate disodium vs. delayed phase images with extracellular cellular contrast agent

Abstract

Objective

To compare the conspicuity of hepatocellular carcinoma (HCC) on hepatobiliary phase of gadoxetate disodium-enhanced vs. delayed phase of gadodiamide-enhanced MR images, relative to liver function.

Methods and materials

We retrospectively identified 86 patients with newly diagnosed HCC between 2010 and 2013 and recorded the severity of liver disease by Child-Pugh class (CPC). 38 patients had gadodiamide-enhanced 5-min delayed and 48 had gadoxetate disodium-enhanced 20-min delayed hepatobiliary MR images. The conspicuity of 86 HCCs (mean size, 2.7 cm) was graded visually on a 3-point scale and quantified by liver-to-tumor contrast ratios (LTC). The relative liver parenchymal enhancement (RPE) was measured. For different CPCs, we compared the conspicuity of HCC and RPE between gadodiamide and gadoxetate.

Results

In patients with CPC A, the visual conspicuity and LTC of the 27 HCCs imaged with gadodiamide were significantly lower than those of the 38 HCCs with gadoxetate (P < 0.01, <0.01, respectively). RPE was lower in gadodiamide scans than gadoxetate scans (P < 0.01). Conversely, in patients with CPC B and C, HCCs appeared more frequently as definite hypointensity when imaged with gadodiamide (72.7%, 8/11) than gadoxetate (20%, 2/10, P = 0.03). LTC (mean 18.1 vs. 7.5, P = 0.04) and RPE (mean 75.5 vs. 45.4, P = 0.04) was significantly higher in the gadodiamide than gadoxetate scans.

Conclusion

In patients with compromised liver function, hypointensity of HCC is more conspicuous in the gadodiamide delayed phase than the gadoxetate hepatobiliary phase. This likely reflects the high extracellular accumulation of gadodiamide and poor hepatocyte uptake of gadoxetate in patients with compromised liver function.

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The “manta ray” pelvis

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The emotional rollercoaster of battling cancer – Philly.com

images?q=tbn:ANd9GcTe2exLkjxqjaaJzBd18UycupXAeEIbegicm-xpEtXklQV6OT-6vHZjKx2RUFohKRs5fyLhXG3n

Philly.com

The emotional rollercoaster of battling cancer
Philly.com
And because salivary glands were also hit with radiation, swallowing any kind of food is difficult, because it's too dry. If you live long enough, it can take two years for things to improve, but taste will never return to 100 percent normal. I lose 30 …

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THYROID STIMULATING ANTIBODIES ARE HIGHLY PREVALENT IN HASHIMOTO'S THYROIDITIS AND ASSOCIATED ORBITOPATHY.

THYROID STIMULATING ANTIBODIES ARE HIGHLY PREVALENT IN HASHIMOTO'S THYROIDITIS AND ASSOCIATED ORBITOPATHY.

J Clin Endocrinol Metab. 2016 Mar 10;:jc20161220

Authors: Kahaly GJ, Diana T, Glang J, Kanitz M, Pitz S, König J

Abstract
CONTEXT: Thyroid-associated orbitopathy (TAO) rarely occurs in patients with Hashimoto's thyroiditis (HT).
OBJECTIVE: There is evidence that TSH receptor (TSHR) stimulating antibodies (TSAb) play a role in the pathogenesis of TAO. In this report, the prevalence of TSAb in HT patients with and without TAO was studied.
DESIGN: Longitudinal observational study Setting: Academic joint thyroid-eye clinic Subjects: A total of 1055 subjects were included Methods: TSAb was measured with a FDA-cleared bioassay that utilizes CHO cells expressing a chimeric TSHR and a cAMP response element-dependent luciferase. Results of TSAb activity were reported as percentage of specimen-to-reference ratio (SRR%, cut-off >140%).
MAIN OUTCOME MEASURE: Association of TSAb with the risk of TAO in patients with HT.
RESULTS: Of 700 consecutive and unselected patients with HT, 44 (6%) had overt TAO. Patients with HT+TAO were older (p<0.001), heavy smoker (p=0.032), and clustered less with autoimmune diseases (p=0.005). All healthy controls were TSAb negative. In contrast, serum was TSAb positive in 30/44 (68.2%) and 36/656 (5.5%, p<0.001) patients with HT+TAO and HT, respectively. Compared to patients with HT only, serum TSAb levels were higher in HT+TAO (Median SRR%, 25% and 75% percentile): 45, 35-65 vs. 192.5, 115-455.3, p<0.001. Highest TSAb values were noted in patients with active and severe TAO versus those with mild and inactive TAO: 486, 392-592 versus 142, 73-192.5, p<0.001. The odds ratio (OR) of TSAb-positivity for the risk of TAO adjusted for gender and age was 55.9 (95% CI 24.6-127, p<0.0001), while the OR per ten-fold change in TSAb SRR% (quantitative TSAb) was 133 (95% CI 45-390, p<0.0001). The area under the ROC-curve for qualitative and quantitative TSAb was 87.2% (95% CI 80.6-93.8) and 89.4% (95% CI 84.1-94.7), respectively.
CONCLUSIONS: TSAb is strongly associated with TAO in HT and TSAb may contribute to the pathophysiology of TAO.

PMID: 26964732 [PubMed - as supplied by publisher]

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Ethical Considerations When Counseling Patients With Thyroid Cancer About Surgery vs Observation-REPLY.

Ethical Considerations When Counseling Patients With Thyroid Cancer About Surgery vs Observation-REPLY.

JAMA Otolaryngol Head Neck Surg. 2016 Mar 10;

Authors: Stack BC, Angelos P

PMID: 26966863 [PubMed - as supplied by publisher]

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Utility of Diagnostic Molecular Markers for Evaluation of Indeterminate Thyroid Nodules.

Utility of Diagnostic Molecular Markers for Evaluation of Indeterminate Thyroid Nodules.

JAMA Otolaryngol Head Neck Surg. 2016 Mar 10;

Authors: Smith RB, Ferris RL

PMID: 26967656 [PubMed - as supplied by publisher]

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Ethical Considerations When Counseling Patients With Thyroid Cancer About Surgery vs Observation.

Ethical Considerations When Counseling Patients With Thyroid Cancer About Surgery vs Observation.

JAMA Otolaryngol Head Neck Surg. 2016 Mar 10;

Authors: Morris LG, Wong RJ, Tuttle RM

PMID: 26968006 [PubMed - as supplied by publisher]

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En bloc resection of a C-1 lateral mass osteosarcoma: technical note.

En bloc resection of a C-1 lateral mass osteosarcoma: technical note.

J Neurosurg Pediatr. 2016 Mar 11;:1-7

Authors: Clarke MJ, Price DL, Cloft HJ, Segura LG, Hill CA, Browning MB, Brandt JM, Lew SM, Foy AB

Abstract
Osteosarcoma is an aggressive primary bone tumor. It is currently treated with multimodality therapy including en bloc resection, which has been demonstrated to confer a survival benefit over intralesional resection. The authors present the case of an 8-year-old girl with a C-1 lateral mass osteosarcoma, which was treated with a 4-stage en bloc resection and spinal reconstruction. While technically complex, the feasibility of en bloc resection for spinal osteosarcoma should be explored in the pediatric population.

PMID: 26966885 [PubMed - as supplied by publisher]

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The Preventable Shunt Revision Rate: a potential quality metric for pediatric shunt surgery.

The Preventable Shunt Revision Rate: a potential quality metric for pediatric shunt surgery.

J Neurosurg Pediatr. 2016 Mar 11;:1-9

Authors: Venable GT, Rossi NB, Morgan Jones G, Khan NR, Smalley ZS, Roberts ML, Klimo P

Abstract
OBJECTIVE Shunt surgery consumes a large amount of pediatric neurosurgical health care resources. Although many studies have sought to identify risk factors for shunt failure, there is no consensus within the literature on variables that are predictive or protective. In this era of "quality outcome measures," some authors have proposed various metrics to assess quality outcomes for shunt surgery. In this paper, the Preventable Shunt Revision Rate (PSRR) is proposed as a novel quality metric. METHODS An institutional shunt database was queried to identify all shunt surgeries performed from January 1, 2010, to December 31, 2014, at Le Bonheur Children's Hospital. Patients' records were reviewed for 90 days following each "index" shunt surgery to identify those patients who required a return to the operating room. Clinical, demographic, and radiological factors were reviewed for each index operation, and each failure was analyzed for potentially preventable causes. RESULTS During the study period, there were 927 de novo or revision shunt operations in 525 patients. A return to the operating room occurred 202 times within 90 days of shunt surgery in 927 index surgeries (21.8%). In 67 cases (33% of failures), the revision surgery was due to potentially preventable causes, defined as inaccurate proximal or distal catheter placement, infection, or inadequately secured or assembled shunt apparatus. Comparing cases in which failure was due to preventable causes and those in which it was due to nonpreventable causes showed that in cases in which failure was due to preventable causes, the patients were significantly younger (median 3.1 vs 6.7 years, p = 0.01) and the failure was more likely to occur within 30 days of the index surgery (80.6% vs 64.4% of cases, p = 0.02). The most common causes of preventable shunt failure were inaccurate proximal catheter placement (33 [49.3%] of 67 cases) and infection (28 [41.8%] of 67 cases). No variables were found to be predictive of preventable shunt failure with multivariate logistic regression. CONCLUSIONS With economic and governmental pressures to identify and implement "quality measures" for shunt surgery, pediatric neurosurgeons and hospital administrators must be careful to avoid linking all shunt revisions with "poor" or less-than-optimal quality care. To date, many of the purported risk factors for shunt failure and causes of shunt revision surgery are beyond the influence and control of the surgeon. We propose the PSRR as a specific, meaningful, measurable, and-hopefully-modifiable quality metric for shunt surgery in children.

PMID: 26966884 [PubMed - as supplied by publisher]

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Implications of patient-borne costs associated with pediatric neurosurgical care in eastern Africa.

Implications of patient-borne costs associated with pediatric neurosurgical care in eastern Africa.

J Neurosurg Pediatr. 2016 Mar 11;:1-9

Authors: Awori J, Strahle J, Okechi H, Davis MC

Abstract
OBJECTIVE Pediatric neurosurgery can be highly cost-effective even in the developing world, but delivery of these services is hampered by resource limitations at the levels of both health care infrastructure and individual patients. Few studies have evaluated costs borne by neurosurgical patients in the developing world and their potential implications for efficient and effective delivery of care in this population. METHODS The families of 40 pediatric neurosurgery patients were surveyed in February 2015 at the AIC Kijabe Hospital in Kijabe, Kenya. Costs associated with obtaining inpatient care were assessed. RESULTS Patient families were charged an average of US $539.44 for neurosurgical services, representing 132% of their annual income. Indirect expenses (transport, food and lodging, lost wages) constituted US $79.37, representing 14.7% of the overall cost and 19.5% of their annual income. CONCLUSIONS Expansion of pediatric neurosurgical services throughout the developing world necessitates increased attention to seemingly insignificant expenses that are absorbed by patients and their families. Even when all direct costs are covered at the institutional or national level, without additional assistance, some patients may be too poor to obtain even "free" neurosurgical care.

PMID: 26966883 [PubMed - as supplied by publisher]

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Anti-CD137 monoclonal antibodies and adoptive T cell therapy: a perfect marriage?

Abstract

CD137(4-1BB) costimulation and adoptive T cell therapy strongly synergize in terms of achieving maximal efficacy against experimental cancers. These costimulatory biological functions of CD137 have been exploited by means of introducing the CD137 signaling domain in clinically successful chimeric antigen receptors and to more efficiently expand T cells in culture. In addition, immunomagnetic sorting of CD137-positive T cells among tumor-infiltrating lymphocytes selects for the fittest antitumor T lymphocytes for subsequent cultures. In mouse models, co-infusion of both agonist antibodies and T cells attains marked synergistic effects that result from more focused and intense cytolytic activity visualized under in vivo microscopy and from more efficient entrance of T cells into the tumor through the vasculature. These several levels of dynamic interaction between adoptive T cell therapy and CD137 offer much opportunity to raise the efficacy of current cancer immunotherapies.

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Fate of Coiled Aneurysms with Minor Recanalization at 6 Months: Rate of Progression to Further Recanalization and Related Risk Factors.

Fate of Coiled Aneurysms with Minor Recanalization at 6 Months: Rate of Progression to Further Recanalization and Related Risk Factors.

AJNR Am J Neuroradiol. 2016 Mar 10;

Authors: Jeon JP, Cho YD, Rhim JK, Yoo DH, Cho WS, Kang HS, Kim JE, Han MH

Abstract
BACKGROUND AND PURPOSE: Minor recanalization in coiled aneurysms may remain stable with time or may progress to major recanalization. Our aim was to monitor the aneurysms displaying minor recanalization in imaging studies at 6 months, gauging major recanalization rates and related risk factors through extended follow-up.
MATERIALS AND METHODS: Sixty-five aneurysms (in 65 patients) showing minor recanalization in follow-up imaging at 6 months were reviewed retrospectively. Medical records and radiologic data accruing during extended monitoring (mean, 24.8 ± 8.2 months) were assessed. Univariate and multivariate analyses were conducted to identify risk factors for progression from minor-to-major recanalization.
RESULTS: Progression to major recanalization was observed in 24 (36.9%) of the initially qualifying aneurysms during a follow-up of 112.5 aneurysm-years, for an annual rate of 17.84% per aneurysm-year. Progression was determined chronologically as follows: 14 (58.3%) at 6 months, 8 (33.3%) at 18 months, and 2 (8.4%) at 30 months. Stent deployment significantly decreased the occurrence of major recanalization (OR = 0.22, P = .03), whereas antiplatelet therapy (OR = 0.82, P = .75), posterior location (OR = 0.24, P = .20), and second coiling for recanalized aneurysms (OR = 0.96, P = .96) were unrelated.
CONCLUSIONS: Our analysis determined a 36.9% rate of major recanalization during a follow-up of 112.5 aneurysm-years in coiled aneurysms showing minor recanalization at 6 months. Stent deployment alone conferred a protective effect, preventing further recanalization without additional treatment. Given the fair probability of late major recanalization, aneurysms showing minor recanalization at 6 months should be monitored diligently, particularly in the absence of stent placement.

PMID: 26965468 [PubMed - as supplied by publisher]

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Endovascular Management of Tandem Occlusion Stroke Related to Internal Carotid Artery Dissection Using a Distal to Proximal Approach: Insight from the RECOST Study.

Endovascular Management of Tandem Occlusion Stroke Related to Internal Carotid Artery Dissection Using a Distal to Proximal Approach: Insight from the RECOST Study.

AJNR Am J Neuroradiol. 2016 Mar 10;

Authors: Marnat G, Mourand I, Eker O, Machi P, Arquizan C, Riquelme C, Ayrignac X, Bonafé A, Costalat V

Abstract
BACKGROUND AND PURPOSE: Internal carotid artery dissection is a common cause of stroke in young adults. It may be responsible for tandem occlusion defined by a cervical steno-occlusive carotid wall hematoma associated with an intracranial large-vessel stroke. Intravenous thrombolysis is associated with a poor clinical outcome in these cases, and endovascular treatment has not been specifically evaluated to date. Our aim was to evaluate endovascular treatment technical and clinical efficiency in this specific occlusion topography, in comparison with treatment of isolated anterior circulation stroke.
MATERIALS AND METHODS: As part of our ongoing prospective stroke data base started in August 2009 (Prognostic Factors Related to Clinical Outcome Following Thrombectomy in Ischemic Stroke [RECOST] Study), we analyzed all carotid artery dissection tandem occlusion strokes and isolated anterior circulation occlusions. All patients were selected for endovascular treatment according to clinical-radiologic mismatch, NIHSS ≥ 7 and DWI-ASPECTS ≥5, within 6 hours after onset. For carotid artery dissection, the revascularization procedure consisted first of distal recanalization by a stent retriever in the intracranial vessel. Following assessment of the circle of Willis, internal carotid artery stent placement was only performed in case of insufficiency. Carotid artery dissection treatment efficacy, safety, and clinical outcome were compared with the results of the isolated anterior circulation occlusion cohort.
RESULTS: Two hundred fifty-eight patients with an anterior circulation stroke were analyzed, including 57 with tandem occlusions (22%); among them, 20 were carotid artery dissection-related occlusions (7.6%). The median age of patients with tandem occlusions with internal carotid dissection was 52.45 versus 66.85 years for isolated anterior circulation occlusion (P < .05); the mean initial NIHSS score was 17.53 ± 4.11 versus 17.55 ± 4.8 (P = .983). The median DWI-ASPECTS was 6.05 versus 6.64 (P = .098), and the average time from onset to puncture was 4.38 for tandem occlusions versus 4.53 hours in isolated anterior circulation occlusion (P = .704). Complication rates and symptomatic intracranial hemorrhage were comparable in both groups (5% versus 3%, P = .49). The duration of the procedure was significantly prolonged in case of tandem occlusion (80.69 versus 65.45 minutes, P = .030). Fourteen patients with carotid artery dissection (70%) had a 3-month mRS of ≤ 2, without a significant difference from patients with an isolated anterior circulation occlusion (44%, P = .2). Only 5 carotid artery dissections (25%) necessitated cervical stent placement. No early ipsilateral stroke recurrence was recorded, despite the absence of stent placement in 15 patients (75%) with carotid artery dissection.
CONCLUSIONS: Mechanical endovascular treatment of carotid artery dissection tandem occlusions is safe and effective compared with isolated anterior circulation occlusion stroke therapy. Hence, a more conservative approach with stent placement only in cases of circle of Willis insufficiency may be a reliable and safe strategy.

PMID: 26965467 [PubMed - as supplied by publisher]

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Performance of CT ASPECTS and Collateral Score in Risk Stratification: Can Target Perfusion Profiles Be Predicted without Perfusion Imaging?

Performance of CT ASPECTS and Collateral Score in Risk Stratification: Can Target Perfusion Profiles Be Predicted without Perfusion Imaging?

AJNR Am J Neuroradiol. 2016 Mar 10;

Authors: Dehkharghani S, Bammer R, Straka M, Bowen M, Allen JW, Rangaraju S, Kang J, Gleason T, Brasher C, Nahab F

Abstract
BACKGROUND AND PURPOSE: Endovascular trials suggest that revascularization benefits a subset of acute ischemic stroke patients with large-artery occlusion and small-core infarct volumes. The objective of our study was to identify thresholds of noncontrast CT-ASPECTS and collateral scores on CT angiography that best predict ischemic core volume thresholds quantified by CT perfusion among patients with acute ischemic stroke.
MATERIALS AND METHODS: Fifty-four patients with acute ischemic stroke (<12 hours) and MCA/intracranial ICA occlusion underwent NCCT/CTP during their initial evaluation. CTP analysis was performed on a user-independent platform (RApid processing of PerfusIon and Diffusion), computing core infarct (defined as CBF of <30% normal). A target mismatch profile consisting of infarction core of ≤50 mL was selected to define candidates with acute ischemic stroke likely to benefit from revascularization.
RESULTS: NCCT-ASPECTS of ≥9 with a CTA collateral score of 3 had 100% specificity for identifying patients with a CBF core volume of ≤50 mL. NCCT-ASPECTS of ≤6 had 100% specificity for identifying patients with a CBF core volume of >50 mL. In our cohort, 44 (81%) patients had an NCCT-ASPECTS of ≥9, a CTA collateral score of 3, or an NCCT-ASPECTS of ≤6.
CONCLUSIONS: Using an NCCT-ASPECTS of ≥9 or a CTA collateral score of 3 best predicts CBF core volume infarct of ≤50 mL, while an NCCT-ASPECTS of ≤6 best predicts a CBF core volume infarct of >50 mL. Together these thresholds suggest that a specific population of patients with acute ischemic stroke not meeting such profiles may benefit most from CTP imaging to determine candidacy for revascularization.

PMID: 26965466 [PubMed - as supplied by publisher]

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Evaluating Permeability Surface-Area Product as a Measure of Blood-Brain Barrier Permeability in a Murine Model.

Evaluating Permeability Surface-Area Product as a Measure of Blood-Brain Barrier Permeability in a Murine Model.

AJNR Am J Neuroradiol. 2016 Mar 10;

Authors: Weidman EK, Foley CP, Kallas O, Dyke JP, Gupta A, Giambrone AE, Ivanidze J, Baradaran H, Ballon DJ, Sanelli PC

Abstract
BACKGROUND AND PURPOSE: Permeability surface-area product has been suggested as a marker for BBB permeability with potential applications in clinical care and research. However, few studies have demonstrated its correlation with actual quantitative measurements of BBB permeability. Our aim was to demonstrate the correlation of quantitative permeability surface-area product and BBB permeability in a murine model by histologic confirmation.
MATERIALS AND METHODS: Coronal MR imaging was performed on mice treated with mannitol (n = 6) for disruption of the BBB and controls treated with saline (n = 5). Permeability surface-area product was determined by ROI placement and was compared between saline- and mannitol-treated mice. Correlation was made with contrast-enhancement measurements and immunohistologic-stained sections of tripeptidyl peptidase-1 distribution in mice treated with mannitol and saline followed by injection of a viral vector containing the CLN2 gene, which directs production of tripeptidyl peptidase-1.
RESULTS: Significantly increased permeability surface-area product was seen in mannitol- compared with saline-treated mice in the whole brain (P = .008), MCA territory (P = .014), and mixed vascular territories (P = .008). These findings were compared with contrast-enhancement measurements of BBB permeability and were correlated with immunohistologic-stained sections demonstrating BBB permeability to a large vector.
CONCLUSIONS: Permeability surface-area product is increased in situations with known disruptions of the BBB, as evidenced by immunologic staining of large-vector passage through the BBB and concordance with contrast-enhancement measurements in a murine model. Quantitative permeability surface-area product has potential as an imaging marker of BBB permeability.

PMID: 26965465 [PubMed - as supplied by publisher]

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Quantitative Susceptibility Mapping in Cerebral Cavernous Malformations: Clinical Correlations.

Quantitative Susceptibility Mapping in Cerebral Cavernous Malformations: Clinical Correlations.

AJNR Am J Neuroradiol. 2016 Mar 10;

Authors: Tan H, Zhang L, Mikati AG, Girard R, Khanna O, Fam MD, Liu T, Wang Y, Edelman RR, Christoforidis G, Awad IA

Abstract
BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been shown to assess iron content in cerebral cavernous malformations. In this study, our aim was to correlate lesional iron deposition assessed by quantitative susceptibility mapping with clinical and disease features in patients with cerebral cavernous malformations.
MATERIALS AND METHODS: Patients underwent routine clinical scans in addition to quantitative susceptibility mapping on 3T systems. Data from 105 patients met the inclusion criteria. Cerebral cavernous malformation lesions identified on susceptibility maps were cross-verified by T2-weighted images and differentiated on the basis of prior overt hemorrhage. Mean susceptibility per cerebral cavernous malformation lesion (χ̄lesion) was measured to correlate with lesion volume, age at scanning, and hemorrhagic history. Temporal rates of change in χ̄lesion were evaluated in 33 patients.
RESULTS: Average χ̄lesion per patient was positively correlated with patient age at scanning (P < .05, 4.1% change with each decade of life). Cerebral cavernous malformation lesions with prior overt hemorrhages exhibited higher χ̄lesion than those without (P < .05). Changes in χ̄lesion during 3- to 15-month follow-up were small in patients without new hemorrhage between the 2 scans (bias = -0.0003; 95% CI, -0.06-0.06).
CONCLUSIONS: The study revealed a positive correlation between mean quantitative susceptibility mapping signal and patient age in cerebral cavernous malformation lesions, higher mean quantitative susceptibility mapping signal in hemorrhagic lesions, and minimum longitudinal quantitative susceptibility mapping signal change in clinically stable lesions. Quantitative susceptibility mapping has the potential to be a novel imaging biomarker supplementing conventional imaging in cerebral cavernous malformations. The clinical significance of such measures merits further study.

PMID: 26965464 [PubMed - as supplied by publisher]

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Risk factors for persistent disease in papillary thyroid carcinoma with lymph node metastasis.

Risk factors for persistent disease in papillary thyroid carcinoma with lymph node metastasis.

Nucl Med Commun. 2016 Mar 10;

Authors: Oral A, Yazici B, Akgün A, Hassoy H, Özcan Z

Abstract
PURPOSE: It is known that the presence of neck lymph node (LN) metastasis is correlated with persistent disease in papillary thyroid carcinoma (PTC) patients. After appropriate therapy, most patients become disease free, whereas some may still have persistent disease. The present study aimed to determine the potential variables affecting the clinical course of the disease and persistent disease patterns in PTC patients with LN metastasis.
MATERIALS AND METHODS: The study group included consecutive PTC patients with LN metastasis. Clinicopathological characteristics and persistent disease pattern during the follow-up period were examined to identify risk factors for persistent disease using univariate and multivariate analyses.
RESULTS: At the end of a median follow-up of 84 months, 90 (69%) patients became disease free and 40 (31%) patients had persistent disease. Univariate analysis showed that male sex, older age at initial diagnose (≥45 years), larger tumor size (>4 cm), presence of lateral cervical LN metastasis, extrathyroidal invasion, and higher number of metastatic LN (≥10) were significant predictors for persistent disease. Multivariate analysis showed that extrathyroidal involvement, presence of lateral cervical LN metastasis, and older age at initial diagnosis (≥45 years) were independent predictors for persistent disease.
CONCLUSION: Despite the presence of LN involvement, most patients may become disease free with therapy. Patients with extrathyroidal invasion, lateral cervical LN involvement, and those at least 45 years old at initial diagnosis are more likely to have persistent disease. However, disease control can be achieved with close clinical follow-up and therapy.

PMID: 26967062 [PubMed - as supplied by publisher]

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Rise in differentiated thyroid cancer incidence in our hospital is not related with an increased incidental microcarcinoma detection.

Rise in differentiated thyroid cancer incidence in our hospital is not related with an increased incidental microcarcinoma detection.

Rev Clin Esp. 2016 Mar 7;

Authors: Ruiz G, Carral F, Tinoco R, Ayala C

PMID: 26964889 [PubMed - as supplied by publisher]

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Treatment patterns of adjuvant interferon-[alpha]2b for high-risk melanoma: a retrospective study of the Grupo Espanol Multidisciplinar de Melanoma - Prima study.

Adjuvant interferon-[alpha]2b (IFN-[alpha]2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-[alpha]2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-[alpha]2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-[alpha]2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-[alpha]2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-[alpha]2b treatment provided a benefit consistent with that described previously. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://ift.tt/1hexVwJ. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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The Merits of a Two-Day Evidence-Based Medicine Course for Surgical Residents.

The Merits of a Two-Day Evidence-Based Medicine Course for Surgical Residents.

World J Surg. 2016 Mar 10;

Authors: Ubbink DT, Legemate DA, Koelemay MJ

Abstract
BACKGROUND: Over 10 years ago, we introduced a two-day, evidence-based surgery course for surgical residents. During the last 4 years, we evaluated its effect on the participants' evidence-based medicine (EBM) knowledge and skills.
METHODS: Between 2012 and 2015, six courses were organised for residents of various surgical specialties of allied hospitals in the Amsterdam educational district. The courses covered the literature search, critical appraisal of surgical papers, and how to communicate and weigh the benefits and harms of surgical interventions. Proficiency regarding interpreting evidence was tested before and directly after the course using a modified Berlin questionnaire.
RESULTS: One hundred participants attended the courses, comprising residents in surgery (61 %), orthopaedics (16 %), urology (7 %), plastic surgery (7 %), and surgical PhD students (9 %), most of whom had already been taught EBM during their medical curriculum. Pre-course score levels were already fairly high (6.19 out of 10), but scores after the course were significantly higher (7.04); mean difference 0.85 (95 % confidence interval 0.4-1.3). No significant differences were observed among the surgical specialties. Attendees highly appreciated the course.
CONCLUSIONS: A two-day, evidence-based surgery course improved EBM aptitude of surgical residents. Hence, the course appears useful to refresh the EBM paradigm among future Dutch surgeons.

PMID: 26964544 [PubMed - as supplied by publisher]

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Risk factors for persistent disease in papillary thyroid carcinoma with lymph node metastasis.

Risk factors for persistent disease in papillary thyroid carcinoma with lymph node metastasis.

Nucl Med Commun. 2016 Mar 10;

Authors: Oral A, Yazici B, Akgün A, Hassoy H, Özcan Z

PMID: 26967062 [PubMed - as supplied by publisher]

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Assessment of Vibratory Characteristics in Children Following Airway Reconstruction Using Flexible and Rigid Endoscopy and Stroboscopy.

http:--archotol.jamanetwork.com-images-P

Assessment of Vibratory Characteristics in Children Following Airway Reconstruction Using Flexible and Rigid Endoscopy and Stroboscopy.

JAMA Otolaryngol Head Neck Surg. 2015 Oct;141(10):882-7

Authors: Zacharias SR, Weinrich B, Brehm SB, Kelchner L, Deliyski D, Tabangin M, de Alarcon A

Abstract
IMPORTANCE: Up to half of children have substantial dysphonia after airway reconstruction. Visual assessment of vocal function is valuable. Feasibility of flexible and rigid endoscopy has been reported; however, the clinical utility of stroboscopy has not been examined. Rating of vibratory characteristics, such as mucosal wave and amplitude of vibration, is essential for the development of interventions to improve voice outcomes.
OBJECTIVE: To examine (1) clinicians' ratings of anatomical and physiological features in children following airway reconstruction on initial voice evaluation using videolaryngostroboscopy and (2) the relationship of age to the type of endoscopy used.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of 32 patients aged 3 to 21 years evaluated for post–airway reconstruction dysphonia between July 2011 and July 2012 at a quaternary care children's hospital.
INTERVENTIONS: Clinical voice evaluation protocol including rigid and/or flexible endoscopy with stroboscopy.
MAIN OUTCOMES AND MEASURES: Demographic and voice quality characteristics were collected. The ability to complete endoscopy and ratings of anatomical and/or physiological features were assessed by a consensus of 4 clinicians. A t test was used to determine whether age was a significant factor in successful completion of videolaryngostroboscopy.
RESULTS: Of 31 children who underwent flexible videolaryngostroboscopy, 22 (71%) examinations were completed with a distal chip endoscope and 9 (29%) with a fiberoptic. Significant differences were found in age between children who completed the distal chip vs. fiberoptic examination (mean [SD], 7.3 [2.7] vs. 5.5 [6.2] years; P = .05). Rigid endoscopy was attempted for 14 (44%) of 32 patients; 9 examinations (64%) were successful. Significant differences were found in age between patients for whom a rigid endoscopy could be successfully completed vs. those for whom it was not (mean [SD], 12.9 [3.4] vs. 6.2 [2.1] years; P < .001). Eighteen (56%) were glottic phonators, 8 (25%) supraglottic, and 6 (19%) aphonic. Vibratory characteristics were visible in 10 of 37 examinations (27%); 6 (16%) had ratable characteristics.
CONCLUSIONS AND RELEVANCE: Endoscopy can be successfully completed in most children who have undergone airway reconstruction, most often using a distal chip endoscope.We found that vibratory characteristics were often not assessed adequately using videolaryngostroboscopy. Further work identifying imaging modalities that better display vibratory characteristics, such as high-speed videoendoscopy, may provide new insight into vocal function and lead to a more thorough evaluation.

PMID: 26402578 [PubMed - indexed for MEDLINE]

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MULTIFOCAL CHOROIDITIS IN DISSEMINATED SPOROTRICHOSIS IN PATIENTS WITH HIV/AIDS.

MULTIFOCAL CHOROIDITIS IN DISSEMINATED SPOROTRICHOSIS IN PATIENTS WITH HIV/AIDS.

Retin Cases Brief Rep. 2016 Mar 10;

Authors: Biancardi AL, Freitas DF, Valviesse VR, Andrade HB, de Oliveira MM, do Valle AC, Zancope-Oliveira RM, Galhardo MC, Curi AL

Abstract
PURPOSE: In this article, the authors describe multifocal choroiditis related to disseminated sporotrichosis in patients with HIV/AIDS.
METHODS: We conducted a retrospective observational study of three patients infected with HIV who presented with disseminated sporotrichosis characterized by cutaneous lesions, multifocal choroiditis, and other manifestations, including osteomyelitis and involvement of the bone marrow, larynx, pharynx, and nasal and oral mucosa.
RESULTS: Five eyes of three patients with HIV/AIDS showed multifocal choroiditis related to disseminated sporotrichosis. The CD4 counts ranged from 25 to 53 mm. All patients were asymptomatic visually. The ocular disease was bilateral in two patients. The lesion size ranged from 1/3 to 2 disc diameters. None of the patients had vitritis. Of the 12 lesions, 9 were localized in the posterior pole (Zone 1) and 3 were localized in the mild periphery (Zone 2).
CONCLUSION: Multifocal choroiditis due to disseminated sporotrichosis can occur in profoundly immunosuppressed patients with HIV/AIDS.

PMID: 26967963 [PubMed - as supplied by publisher]

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Patterns of lymphatic spread and the management of eyelid carcinomas.

Patterns of lymphatic spread and the management of eyelid carcinomas.

Auris Nasus Larynx. 2016 Mar 7;

Authors: Hashimoto K, Yasumatsu R, Toh S, Shiratsuchi H, Yoshida T, Nishiyama K, Yoshikawa H, Nakashima T, Nakagawa T

Abstract
OBJECTIVE: Eyelid carcinomas are rare, and the management strategy of regional lymph node metastasis linked to eyelid carcinomas has not been standardized to date. The aim of the present study was to analyze the patterns of regional metastasis and to assess the optimal extent of surgical treatment for lymph node metastasis of eyelid carcinoma.
METHODS: This study was a retrospective review of patient data from a single institution. From a series of 268 eyelid carcinomas, we selected the 21 patients with lymph node metastasis, and we analyzed the patterns of lymphatic spread, approach to treatment and outcomes.
RESULTS: The most common histological type of eyelid carcinoma with regional metastasis was sebaceous carcinoma (17/21, 81.0%). Submandibular area metastases were seen only in the patients with the primary tumor originating in the medial half of the eyelid, but parotid area metastases were seen in both the patients whose tumors had a medial-half origin and those with a lateral-half origin. Although 11 of the 16 patients with parotid-area metastases underwent a tumorectomy or superficial parotidectomy (which resulted in four cases of recurrence in the parotid area), none of the five patients who underwent a total parotidectomy developed parotid-area recurrence. The incidence of regional recurrence of the patients who received adjuvant radiotherapy (14.3%) was lower than that of the patients without adjuvant radiotherapy (57.1%).
CONCLUSION: Continued surveillance and optimal management of regional lymph node metastases are important for the control and survival of eyelid carcinomas.

PMID: 26965587 [PubMed - as supplied by publisher]

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Bilateral haemorrhagic vocal cords with supraglottic bruising following blunt laryngeal trauma.

Bilateral haemorrhagic vocal cords with supraglottic bruising following blunt laryngeal trauma.

J Coll Physicians Surg Pak. 2014 Nov;24 Suppl 3:S235-7

Authors: Sheikh E, Keh S, Vallamkondu V, Khan I, Shakeel M

Abstract
Isolated vocal cord haemorrhage secondary to blunt neck trauma is rare. It can lead to compromised airway in a patient with otherwise minimal clinical findings. The authors report a patient with traumatic haemorrhage in the supraglottis and vocal cords. A 24 years old Caucasian male presented with acute hoarseness, dysphagia, and a tender anterior neck swelling 3 hours after he was punched in his neck. There was no stridor or surgical emphysema. Flexible pharyngolaryngoscopy revealed no endolaryngeal mucosal tear but evidence of bleeding into his true vocal cords. The patient was successfully treated with dexamethasone, analgesia and voice rest. The patient refused to stay in hospital for overnight airway monitoring. The authors believe that all patients presenting with a blunt neck trauma should undergo laryngoscopy for assessment and monitoring of the airway.

PMID: 25518786 [PubMed - indexed for MEDLINE]

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CD5 positivity is an independent adverse prognostic factor in elderly patients with diffuse large B cell lymphoma.

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CD5 positivity is an independent adverse prognostic factor in elderly patients with diffuse large B cell lymphoma.

Virchows Arch. 2015 Nov;467(5):571-82

Authors: Chuang WY, Chang H, Shih LY, Wang PN, Chang YS, Lin TL, Hung YS, Yeh CJ, Ueng SH, Tang TC, Kuo MC, Dunn P, Wu JH, Kao HW, Ou CW, Wan YL, Hsueh C

Abstract
Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. Age over 60 years is one of the five parameters of the International Prognostic Index (IPI), which is the most important clinical prognostic predictor in DLBCL. A previous study on German DLBCL patients over 60 years of age showed that immunoblastic morphology, but not germinal center B cell-like (GCB)/non-GCB subtype, correlated with short survival. We collected 174 DLBCL cases over 60 years of age in Taiwan and performed immunophenotyping and detection of Epstein-Barr virus (EBV)-encoded RNA (EBER) by in situ hybridization. Of the cases, 5.2 % were positive for CD5 and 5.7 % positive for EBER. Neither immunoblastic morphology nor GCB/non-GCB subtype correlated with survival. In univariate analysis, adverse prognostic factors included IPI ≥ 3 (P < 0.000001), B symptoms (P = 0.000075), bone marrow/peripheral blood involvement (P = 0.017), EBER positivity (P = 0.0013), and CD5 positivity (P = 0.016). In multivariate analysis, CD5 positivity was the only independent adverse prognostic factor (HR = 3.16; 95 % CI = 1.34-7.47; P = 0.0087) in addition to IPI ≥ 3 (HR = 3.07; 95 % CI = 1.84-5.11; P = 0.000018). Surprisingly, despite an overall 5.2 % incidence of central nervous system (CNS) relapse in our patients, none of the CD5+ cases experienced CNS relapse (P = 1.00). This is in stark contrast to the more frequent CNS relapse in Japanese CD5+ DLBCL patients. EBER positivity was associated with IPI ≥ 3 (P = 0.010), stage III-IV (P = 0.0082), and B symptoms (P = 0.011). In multivariate analysis, EBER positivity was not an independent adverse prognostic factor (P = 0.81), its effect being due likely to accompanying adverse clinical parameters.

PMID: 26369546 [PubMed - indexed for MEDLINE]

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Impaired orthostatic blood pressure recovery and cognitive performance at two-year follow up in older adults: The Irish Longitudinal Study on Ageing

Abstract

Background

Prospective investigations of the association between impaired orthostatic blood pressure (BP) regulation and cognitive decline in older adults are limited, and findings to-date have been mixed. The aim of this study was to determine whether impaired recovery of orthostatic BP was associated with change in cognitive function over a 2-year period, in a population based sample of community dwelling older adults.

Methods

Data from the first two waves of the Irish Longitudinal Study on Ageing were analysed. Orthostatic BP was measured during a lying to standing orthostatic stress protocol at wave 1 using beat-to-beat digital plethysmography, and impaired recovery of BP at 40 s post stand was investigated. Cognitive function was assessed at wave 1 and wave 2 (2 years later) using the Mini-Mental State Exam (MMSE), verbal fluency and word recall tasks.

Results

After adjustment for measured, potential confounders, and multiple imputation for missing data, the change in the number of errors between waves on the MMSE was 10 % higher [IRR (95 % CI) = 1.10 (0.96, 1.26)] in those with impaired recovery at 40 s. However, this was not statistically significant (p = 0.17). Impaired BP recovery was not associated with change in performance on any of the other cognitive measures.

Conclusions

There was no clear evidence for an association between impaired recovery of orthostatic BP and change in cognition over a 2-year period in this nationally representative cohort of older adults. Longer follow-up and more detailed cognitive testing would be advantageous to further investigate the relationship between orthostatic BP and cognitive decline.

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Evidence of the chemical reaction of 18O-labeled nitrite with CO2 in aqueous buffer of neutral pH and the formation of 18OCO by isotope ratio mass spectrometry

Publication date: Available online 11 March 2016
Source:Nitric Oxide
Author(s): Dimitrios Tsikas, Anke Böhmer, Gerolf Gros, Volker Endeward
Inorganic nitrite (NO2−, O=N-O– ←→ –O-N=O) is the autoxidation product of nitric oxide (NO). Nitrite can also be formed from inorganic nitrate (ONO2−), the major oxidation product of NO in erythrocytes, by the catalytic action of bacterial nitrate reductase in gut and oral microflora. Nitrite can be reduced to NO by certain cellular proteins and enzymes, as well as in the gastric juice under acidic conditions. Hemoglobin, xanthine oxidoreductase and carbonic anhydrase (CA) have been reported to convert nitrite to NO. Renal CA isoforms are involved in the reabsorption of nitrite and may, therefore, play an important role in NO homeostasis. Yet, the mechanisms underlying the action of CA on nitrite are incompletely understood. The nitrate/nitrite system is regarded as a reservoir of NO. We have recently shown that nitrite reacts chemically with carbon dioxide (CO2), the regular substrate of CA. The present communication reports a stable isotope ratio mass spectrometry (IRMS) study on the reaction of NO2− and CO2 performed in 50 mM HEPES buffer of pH 7.4 at 37 °C. By using 18O-labelled nitrite (18O=N-O–/–18O-N=O) and CO2 we observed formation of 18O-labelled CO2. This finding is an unequivocal evidence of the chemical reaction of 18O=N-O–/–18O-N=O with CO2. The reaction is rapid and involves nucleophilic attack of the negatively charged nitrite via one of its oxygen atoms on the partially positively charged CO2 molecule to form the putative intermediate 18O=N-O-CO2–/–O2C-18O-N=O. The by far largest fraction of this intermediate decomposes back to 18O=N-O–/–18O-N=O and CO2. A very small fraction of the intermediate, however, rearranges and finally decomposes to form 18OCO and nitrite. This reaction is slower in the presence of an isolated erythrocytic CA isoform II. In summary, NO2−, CO2 and CA are ubiquitous. The chemical reaction of NO2− with CO2 and its modulation by CA isoforms may play important roles in the transport of nitrite in red blood cells, the kidney and other cells and organs.

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Endovascular techniques for the management of wide-neck intracranial bifurcation aneurysms: A critical review of the literature

Publication date: Available online 11 March 2016
Source:Journal of Neuroradiology
Author(s): Laurent Pierot, Alessandra Biondi
Endovascular treatment is the first line treatment for intracranial aneurysms, but wide-neck aneurysms are often difficult to treat due to the difficulty in stabilizing the coils inside the aneurysm. It is singularly true for wide-neck bifurcation aneurysms (WNBA) as bifurcation branches often arise from the aneurysm neck. To overcome these difficulties, several approaches are available to treat both ruptured and unruptured aneurysms (balloon-assisted coiling and intra-aneurysmal flow disruption), while some techniques are essentially restricted to unruptured aneurysms due to the need of concomitant use of antiplatelet medications (stent-assisted coiling and flow diversion). Several ways of performing balloon-assisted coiling have been proposed for WNBA. Two stent-assisted techniques are available for WNBA (Y-stenting and the waffle-cone technique), but these techniques have yet to be evaluated in large, prospective series. Off-label use of flow diverters in WNBA has been proposed but efficacy has still to be established, and the technique presents unique potential safety issues (the potential modifications of bifurcation branches covered by the flow diverter) that has to be assessed. Intrasaccular flow disruption devices are promising tools for the endovascular treatment of WNBA. The WEB device has been extensively evaluated with prospective, multicenter studies showing high safety and good efficacy.

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Stimulant medication and postural orthostatic tachycardia syndrome: a tale of two cases

Abstract

Stimulant medication may mimic the tachycardia of postural orthostatic tachycardia syndrome. Two case histories illustrate how missing the clinical distinction between a primary dysautonomia and a medication effect may have avoidable adverse consequences.

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Evaluation of the relationship between maxillary sinus floor position and maxillary sinusitis using cone beam computed tomography

Abstract

Objectives

The aim of this study was to evaluate the effect of the relationship between the horizontal position of the maxillary sinus floor and the tooth roots on maxillary sinus pathologies using cone beam computed tomography.

Methods

The patients' age, sex, presence or absence of apical abscesses, and horizontal relationship between the maxillary sinuses and tooth roots were recorded. In total, 228 maxillary sinuses of 114 patients were divided into case and control groups according to whether pathology was present. The horizontal relationship between the tooth roots and the lower wall of the maxillary sinus was categorized into three types. The variables were analyzed using the Chi-square test.

Results

Of 42 apical abscesses, 13 (31 %) were present in the control group and 29 (69 %) were present in the case group. This difference was statistically significant (p = 0.003). Each of the 228 maxillary sinuses was classified according to its horizontal relationship to the tooth root. The most frequently seen relationship was Type II, followed by Type I and III, respectively. Although the control and case groups showed equilibrium in the distribution of Type II and III relationships, maxillary sinus pathologies were significantly less common in Type I (p < 0.001).

Conclusions

This study shows that positioning of the maxillary sinus toward the buccal side (Type I) poses an obstacle to the spread of odontogenic infection to the sinus and that the presence of apical abscesses is correlated with maxillary sinusitis.

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CME: Parkinson-Therapie zwischen Leitlinie und Individualisierung

Idiopathisches Parkinson-Syndrom
Bei der Behandlung des idiopathischen Parkinson-Syndroms müssen im klinischen Alltag die Empfehlungen der Leitlinien an die Bedürfnisse des einzelnen Patienten angepasst werden. Was sind die gängigen Therapieprinzipien und was die Ermessensspielräume einer individualisierten Therapie?

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Scoping review of complexity theory in health services research

Abstract

Background

There are calls for better application of theory in health services research. Research exploring knowledge translation and interprofessional collaboration are two examples, and in both areas, complexity theory has been identified as potentially useful. However, how best to conceptualize and operationalize complexity theory in health services research is uncertain. The purpose of this scoping review was to explore how complexity theory has been incorporated in health services research focused on allied health, medicine, and nursing in order to offer guidance for future application. Given the extensiveness of how complexity theory could be conceptualized and ultimately operationalized within health services research, a scoping review of complexity theory in health services research is warranted.

Methods

A scoping review of published research in English was conducted using CINAHL, EMBASE, Medline, Cochrane, and Web of Science databases. We searched terms synonymous with complexity theory.

Results

We included 44 studies in this review: 27 were qualitative, 14 were quantitative, and 3 were mixed methods. Case study was the most common method. Long-term care was the most studied setting. The majority of research was exploratory and focused on relationships between health care workers. Authors most commonly used complexity theory as a conceptual framework for their study. Authors described complexity theory in their research in a variety of ways. The most common attributes of complexity theory used in health services research included relationships, self-organization, and diversity. A common theme across descriptions of complexity theory is that authors incorporate aspects of the theory related to how diverse relationships and communication between individuals in a system can influence change.

Conclusion

Complexity theory is incorporated in many ways across a variety of research designs to explore a multitude of phenomena.. Although complexity theory shows promise in health services research, particularly related to relationships and interactions, conceptual confusion and inconsistent application hinders the operationalization of this potentially important perspective. Generalizability from studies that incorporate complexity theory is, therefore, difficult. Heterogeneous conceptualization and operationalization of complexity theory in health services research suggests there is no universally agreed upon approach of how to use this theory in health services research. Future research should include clear definitions and descriptions of complexity and how it was used in studies. Clear reporting will aid in determining how best to use complexity theory in health services research.

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Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters.

Fumaric acid esters (FAE) are beneficial in the treatment of psoriasis. However, about a third of psoriasis patients do not respond to FAE. We aimed to determine whether glutathione-S-transferase (GST) M1 and GSTP1 polymorphisms are associated with treatment outcome in psoriasis patients treated with FAE. We studied 84 psoriasis patients who were treated with FAE for 3 months. FAE nonresponders were defined as having psoriasis area and severity improvement index less than 50% after 3-month therapy. GSTM1 genotyping for gene deletion and GSTP1 exon 5 105 Ile->Val polymorphisms were assessed using a high-resolution melting analysis. A dropout rate of 23.8% (20/84) was found; 25% (16/64) were FAE nonresponders. We observed 42 (84/50%) patients with G 9STM1*0 homozygous alleles and 42 (84/50%) patients with one or two active GSTM1 alleles. The Ile/Ile GSTP1 genotype was observed in 37 (84/44%), the Ile/Val GSTP1 genotype in 38 (84/45.2%) patients and the Val/Val GSTP1 genotype in nine (84/10.7%) patients. There was no significant (P>0.05) association between the GST genotypes assessed and the frequency FAE responder status, except for the Val/Val GSTP1 polymorphism, which was a significant (overall model fit; P=0.0012) predictor for nonresponders with an odds ratio of 43.4 (95% confidence interval: 4.2-511.1). The coefficient of regression was 3.9, with a SE of 1.2 as assessed by logistic regression analysis (P=0.0017). The Val/Val GSTP1 polymorphism predicts nonresponders in FAE treatment of psoriasis patients and may therefore serve as a biomarker that enables a laboratory-based pretreatment selection of patients. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Achieving behaviour change for detection of Lynch syndrome using the Theoretical Domains Framework Implementation (TDFI) approach: a study protocol

Abstract

Background

Lynch syndrome is an inherited disorder associated with a range of cancers, and found in 2–5 % of colorectal cancers. Lynch syndrome is diagnosed through a combination of significant family and clinical history and pathology. The definitive diagnostic germline test requires formal patient consent after genetic counselling. If diagnosed early, carriers of Lynch syndrome can undergo increased surveillance for cancers, which in turn can prevent late stage cancers, optimise treatment and decrease mortality for themselves and their relatives. However, over the past decade, international studies have reported that only a small proportion of individuals with suspected Lynch syndrome were referred for genetic consultation and possible genetic testing. The aim of this project is to use behaviour change theory and implementation science approaches to increase the number and speed of healthcare professional referrals of colorectal cancer patients with a high-likelihood risk of Lynch syndrome to appropriate genetic counselling services.

Methods

The six-step Theoretical Domains Framework Implementation (TDFI) approach will be used at two large, metropolitan hospitals treating colorectal cancer patients. Steps are: 1) form local multidisciplinary teams to map current referral processes; 2) identify target behaviours that may lead to increased referrals using discussion supported by a retrospective audit; 3) identify barriers to those behaviours using the validated Influences on Patient Safety Behaviours Questionnaire and TDFI guided focus groups; 4) co-design interventions to address barriers using focus groups; 5) co-implement interventions; and 6) evaluate intervention impact. Chi square analysis will be used to test the difference in the proportion of high-likelihood risk Lynch syndrome patients being referred for genetic testing before and after intervention implementation. A paired t-test will be used to assess the mean time from the pathology test results to referral for high-likelihood Lynch syndrome patients pre-post intervention. Run charts will be used to continuously monitor change in referrals over time, based on scheduled monthly audits.

Discussion

This project is based on a tested and refined implementation strategy (TDFI approach). Enhancing the process of identifying and referring people at high-likelihood risk of Lynch syndrome for genetic counselling will improve outcomes for patients and their relatives, and potentially save public money.

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Patient information and emotional needs across the hip osteoarthritis continuum: a qualitative study

Abstract

Background

Osteoarthritis (OA) is the most common form of arthritis worldwide, affecting a growing number of people in the ageing populations. Currently, it affects about 50 % of all people over 65 years of age. There are no disease-modifying treatments for OA; hence preference-sensitive treatment options include symptom reduction, self-management and surgical joint replacement for suitable individuals. People have both ethical and legal rights to be informed about treatment choices and to actively participate in decision-making. Individuals have different needs; they differ in their ability to understand and make use of the provided information and to sustain behaviour change-dependent treatments over time.

Methods

As a part of a larger research project that aims to develop and test a web-based support tool for patients with hip OA, this paper is a qualitative in-depth study to investigate patients' need for information and their personal emotional needs. We invited 13 patients to participate in individual interviews, which were audiotaped. The audio-tapes were transcribed verbatim and analysed using an inductive thematic analysis approach.

Results

The thematic analysis revealed a pattern of patients' information and emotional needs, captured in several key questions relevant to the different stages of the disease experience. Based on these results and research literature, we developed a model illustrating the patients' disease experience and treatment continuum. Six phases with accompanying key questions were identified, displaying how patients information and emotional needs arise and change in line with the progression of the disease experience, the clinical encounters and the decision-making process. We also identified and included in the model an alternative route that bypasses the surgical treatment option.

Conclusion

Patients with hip OA are in great need of information both at the time of diagnosis and further throughout the disease development and care continuum. Lack of information may result in unnecessary and dysfunctional misconceptions, underuse of potentially helpful treatment options and uninformed decisions. Patients need continuous support from health professionals and their families in order to find and consider effective treatment strategies.

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Αρχειοθήκη ιστολογίου

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Σάββατο 12 Μαρτίου 2016

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