bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Postoperative Thrombosis Prophylaxis on the Recurrence of Chronic Subdural Hematoma After Burr-Hole Drainage
Authors: Licci Maria , Kamenova Maria , Guzman Raphael , Mariani Luigi , Soleman Jehuda
Published: October 2017

Objectives:

Chronic subdural hematoma is a commonly encountered disease in neurosurgic practice, whereas its increasing prevalence is compatible with the ageing population. Recommendations concerning postoperative thrombosis prophylaxis after burr-hole drainage of chronic subdural hematoma are lacking. The aim of this study was to analyze the correlation between recurrence of chronic subdural hematoma and postoperative application of thrombosis prophylaxis.

Design:

Retrospective, consecutive sample of patients undergoing burr-hole drainage for chronic subdural hematoma over 3 years.

Setting:

Single, academic medical center.

Patients:

All patients undergoing surgical evacuation of a chronic subdural hematoma with burr-hole drainage. Exclusion: patients under the age of 18 years, who presented with an acute subdural hematoma and those who underwent a craniotomy.

Interventions:

We compared patients receiving thrombosis prophylaxis treatment after burr-hole drainage of chronic subdural hematoma with those who were not treated. Primary outcome measure was reoperation of chronic subdural hematoma due to recurrence. Secondary outcome measures were thromboembolic and cardiovascular events, hematologic findings, morbidity, and mortality. In addition, a subanalysis comparing recurrence rate dependent on the application time of thrombosis prophylaxis (< 48 vs > 48 hr) was undertaken.

Measurements and Main Results:

Overall recurrence rate of chronic subdural hematoma was 12.7%. Out of the 234 analyzed patients, 135 (57.3%) received postoperative thrombosis prophylaxis (low-molecular-weight heparin) applied subcutaneously. Recurrence of chronic subdural hematoma occurred in the thrombosis prophylaxis group and control group in 12 patients (8.9%) and 17 patients (17.2%), respectively, showing no significant difference (odds ratio, 0.47 [95% CI, 0.21 – 1.04]). A subanalysis comparing recurrence rate of chronic subdural hematoma dependent on the application time of thrombosis prophylaxis (< 48 vs > 48 hr) showed no significant difference either (odds ratio, 2.80 [95% CI, 0.83–9.36]). Higher dosage of thrombosis prophylaxis correlated with recurrence rates of chronic subdural hematoma, both in univariate and multivariate analyses.

Conclusions:

Our data suggest that the application of postoperative thrombosis prophylaxis after burr-hole drainage for chronic subdural hematoma does not result in higher recurrence rates of chronic subdural hematoma. In addition, it seems that early administration of thrombosis prophylaxis (< 48 hr) has no influence on recurrence rates; however, high dosage seems to increase recurrence rates.
Mechanism of Action of Topical Garlic on Wound Healing
Authors: Alhashim Minhal , Lombardo Jamie
Published: October 2017

BACKGROUND

Allicin, the active component of garlic, has been shown to have antimicrobial and anti-inflammatory properties. Garlic has also been used historically by many cultures to heal wounds. Several animal studies have shown that garlic extracts increase the rate of wound healing and decrease the rate of infection.

OBJECTIVE

Fibroblasts play a key role in wound healing. Here we hypothesize that fibroblasts are being activated by allicin, leading to more organized and rapid wound repair.

MATERIALS AND METHODS

Six rats were each given 2 surgical wounds. One side was treated with a 30% garlic ointment while the other was treated with Vaseline for two weeks. A biopsy was taken from each scar site and histopathology with Immunohistochemistry was performed to quantify the number of fibroblasts and proliferating fibroblasts in each site.

RESULTS

The wound biopsies had more proliferating fibroblasts in the scars treated with the 30% garlic ointment than in the scars treated with Vaseline with a p-value of 0.0175 at two weeks post op and 0.081 at 6 week post op.

CONCLUSION

This data tells us that allicin is acting on fibroblasts as there were more proliferating fibroblasts in the garlic treated sites than in the other sites.
Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice
Authors: Guarracino Fabio , Heringlake Matthias , Cholley Bernard , Bettex Dominique , Bouchez Stefaan , Lomivorotov Vladimir V. , Rajek Angela , Kivikko Matti , Pollesello Piero
Published: October 2017

Levosimendan is a calcium sensitizer and adenosine triphosphate–dependent potassium channel opener, which exerts sustained hemodynamic, symptomatic, and organ-protective effects. It is registered for the treatment of acute heart failure, and when inotropic support is considered appropriate. In the past 15 years, levosimendan has been widely used in clinical practice and has also been tested in clinical trials to stabilize at-risk patients undergoing cardiac surgery. Recently, 3 randomized, placebo-controlled, multicenter studies (LICORN, CHEETAH, and LEVO-CTS) have been published reporting on the perioperative use of levosimendan in patients with compromised cardiac ventricular function. Taken together, many smaller trials conducted in the past suggested beneficial outcomes with levosimendan in perioperative settings. By contrast, the latest 3 studies were neutral or inconclusive. To understand the reasons for such dissimilarity, a group of experts from Austria, Belgium, Finland, France, Germany, Italy, Switzerland, and Russia, including investigators from the 3 most recent studies, met to discuss the study results in the light of both the previous literature and current clinical practice. Despite the fact that the null hypothesis could not be ruled out in the recent multicenter trials, we conclude that levosimendan can still be viewed as a safe and effective inodilator in cardiac surgery.
Use of a Dynamic Balance System to Quantify Postural Steadiness and Stability of Individuals with Lower-Limb Amputation: A Pilot Study
Authors: Silver-Thorn M. Barbara , Kempfer Joel , Schnorenberg Alyssa J. , Slavens Brooke A.
Published: October 2017

Introduction

Despite rehabilitation and gait training, the gait of individuals with lower-limb amputation is often asymmetric and falls and/or fear of falling are common. Clinical assessments of balance and stability include the Berg Balance Scale and the Dynamic Gait Index. Biomechanical assessments, conducted largely in research laboratories, are more objective, quantitative, and may provide greater resolution. These biomechanical measures include postural sway during both unilateral and bilateral standing tasks and the dynamic postural response to applied or volitional perturbations. The objective of this study was to investigate the utility of a dynamic balance system, a relatively new clinical tool incorporating dual force plates similar to that used in research laboratories, to assess the postural steadiness and stability of a small, diverse population of persons with lower-limb amputation. The specific aim was to investigate whether differences in balance of persons with amputation due to changes in prosthetic componentry were reflected in the resultant data.

Materials and Methods

Dynamic balance testing was conducted using the Bertec Balance Advantage–Dynamic CDP system on five adult subjects with varying levels of lower-limb amputation. Trials were conducted in both the subjects' current prosthesis and alternative prosthetic componentry after a 1-week acclimation period. Specific tasks included limits of stability, weight-bearing squats, and unilateral stance.

Results

Subjects had difficulty shifting their weight during the limits of stability task; both the maximum excursion and anteroposterior directional control varied with prosthetic componentry. Load sharing also varied with prosthetic componentry. Load sharing became more asymmetric as knee flexion increased during the weight-bearing bilateral squat tasks, with less weight supported on the prosthetic limb. Finally, the metrics for the unilateral stance task varied with prosthetic componentry.

Conclusions

The dynamic balance system tasks and related metrics demonstrated the potential to discern differences in balance in persons with amputation due to changes in prosthetic componentry. Further study is needed to investigate these parameters, their correlation with clinical measures of balance, and the effects of both prosthetic componentry and alignment.
The Etiological Relationship Between Migraine and Sudden Hearing Loss
Authors: Arslan Yildiz , Arslan İlker Burak , Aydin Huriye , Yağiz Özlem , Tokuçoğlu Figen , Çukurova İbrahim
Published: October 2017

Objectives:

To investigate the relationship between sudden sensorineural hearing loss (SSNHL) and migraine, assess the prevalence of migraine in patients with idiopathic SSNHL, and determine a possible common vascular etiopathogenesis for migraine and SSNHL.

Study Design:

Prospective cohort study.

Setting:

Tertiary referral center.

Patients:

This study initially assessed 178 SSNHL cases obtained from the Head and Neck Surgery Clinic patient database at a tertiary hospital in Turkey between January 2011 and March 2016. Ultimately, a total of 61 idiopathic SSNHL patients participated in the present study.

İnterventions:

Diagnostic.

Main Outcome Measures:

Cases with inflammation in the middle or inner ear; a retro cochlear tumor; autoimmune, infectious, functional, metabolic, neoplastic, traumatic, toxic, or vascular causes; Meniere's disease; otosclerosis; multiple sclerosis; and/or cerebrovascular diseases were excluded.

Results:

Of the 61 idiopathic SSHNL patients, 34 were women (55.74%); and 24 (39.34%) had migraine, according to the criteria of the International Headache Society (IHS). The mean age of the migraine patients (Group 1) was 43.83 ± 13.16 years, and that of those without migraine (Group 2) was 51.05 ± 16.49 years. The groups did not significantly differ in terms of age, sex, or SSNHL recovery rates according to the Siegel criteria (p > 0.05). Ten of the migraine patients experienced visual aura, and the recovery rates of this group were higher. Additionally, the rate of total hearing loss was lower in Group 1 (n = 3, 12.5%) than in Group 2 (n = 10, 27%).

Conclusion:

SSNHL patients had a higher prevalence of migraine. Although those with migraine had higher recovery rates, the differences were not statistically significant.
Volume–Outcome Relationships in Extracorporeal Membrane Oxygenation: Retrospective Analysis of Administrative Data From Pennsylvania, 2007–2015
Authors: Huesch Marco D.
Published: October 2017

This article seeks to understand whether a volume–outcome relationship exists in adult extracorporeal membrane oxygenation (ECMO). We examined primary administrative discharge data from the Pennsylvanian Health Care Cost Containment Council for all 2,948 consecutive adults treated with ECMO in Pennsylvania between January 1, 2007, and December 31, 2015. We used a well-fitting backwards stepwise logistic regression to obtain patient-level predicted mortality. Number of cases and risk-adjusted mortality was aggregated by calendar quarter and by hospital. Graphical and correlation analysis was used to understand the volume–outcome relationship, focusing separately on the impact of a hospital’s current scale (annual volume of adult ECMO) and a hospital’s cumulative experience (total cumulative volume of adult ECMO since starting operations). We found that more than 9 years, there was essentially no reduction in overall risk-adjusted mortality in the state. For individual hospitals, once institutions had as few as 50 cases’ total experience or performed just 10 cases annually, there was no clear improvement in outcomes. Patients in hospitals with fewer than 50 cases ever performed appeared objectively less sick compared with patients in hospital with more experience. We conclude that there is little evidence of volume–outcome relationships in adult ECMO in this state, although we acknowledge that the absence of clinical chart data limits these conclusions.
Delayed complications from expanded endonasal surgery for intracranial tumors
Authors: Geltzeiler Mathew N. , Wang Eric W.
Published: October 2017

Purpose of review

Delayed complications after endoscopic endonasal approaches to the skull base, defined as complications greater than 1 month postoperatively, are uncommon. These complications are divided into categories including sinonasal, neuroanatomic, endocrine and vascular. This review highlights the most up-to-date advancements and reviews the management of delayed complications for skull base patients.

Recent findings

Over the last 10 years, the field of endoscopic endonasal skull base surgery has expanded with new data highlighting the long-term patient outcomes. The majority of patients experience increased quality of life (QOL) after these interventions. However, delayed complications including alterations to sinonasal function, delayed encephaloceles from the bony skull base defect and resulting endocrinopathies can significantly impact patient's QOL. Awareness of these complications and their current management is valuable for endoscopic surgeons.

Endonasal approaches to the skull base are safe and well tolerated in properly selected patients. This article highlights the delayed complications that require recognition and management by skull base surgeons to ensure the best possible care for patients.
Wilson's Disease in Children
Authors: Socha Piotr , Janczyk Wojciech , Dhawan Anil , Baumann Ulrich , D'Antiga Lorenzo , Tanner Stuart , Iorio Raffaele , Vajro Pietro , Houwen Roderick , Fischler Björn , Dezsofi Antal , Hadzic Nedim , Hierro Loreto , Jahnel Jörg , McLin Valérie , Nobili Valerio , Smets Francoise , Verkade Henkjan J. , Debray Dominique
Published: October 2017

Background:

Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24‐hour urinary copper excretion. Final diagnosis of WD can be established using a diagnostic scoring system based on symptoms, biochemical tests assessing copper metabolism, and molecular analysis of mutations in the ATP7B gene. Pharmacological treatment is life‐long and aims at removal of copper excess by chelating agents as D‐penicillamine, trientine, or inhibition of intestinal copper absorption with zinc salts. Acute liver failure often requires liver transplantation. This publication aims to provide recommendations for diagnosis, treatment, and follow‐up of WD in children.

Methods:

Questions addressing the diagnosis, treatment, and follow‐up of WD in children were formulated by a core group of ESPGHAN members. A systematic literature search on WD using MEDLINE, EMBASE, Cochrane Database from 1990 to 2016 was performed focusing on prospective and retrospective studies in children. Quality of evidence was assessed according to the GRADE system. Expert opinion supported recommendations where the evidence was regarded as weak. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique.
Splenic Rupture in Children With Portal Hypertension
Authors: Waisbourd‐Zinman Orith , Shah Amit , Lin Henry C. , Rand Elizabeth B.
Published: October 2017

Introduction:

Massive splenomegaly from portal hypertension (PHTN) in children raises the specter of splenic rupture; however, the incidence, etiology, and risk of rupture have not been studied, nor have existing practices to reduce risk. We therefore performed an international survey to describe the splenic rupture cases in PHTN and to describe the existing empirical practice among hepatologists.

Methods:

A questionnaire was constructed to elicit cases of splenic rupture and collect hepatologists’ common practices for prevention of splenic rupture. Pediatric hepatologists working in selected tertiary academic centers in the United States, Canada, and the United Kingdom were contacted.

Results:

Hepatologists from 30 of 35 centers who met the inclusion criteria replied to the survey. Thirteen cases of splenic rupture were described of which 11 resulted from trauma. In the opinion of the practitioners, high‐risk activities were football, hockey, and wrestling. Sixty‐one percent recommended total restriction from high‐risk activities. Seventy‐four percent stated that platelet count had no effect on this decision and 61% advised a spleen guard for certain activities.

Conclusions:

Splenic rupture in patients with PHTN and splenomegaly seems to be rare. The reported splenic rupture cases were mostly related to falling (and not to participation in sports). There was general agreement among hepatologists about restricting high impact sports. There was variation in recommendations regarding the use of a spleen guard. The authors recommend use of spleen guards in children with splenomegaly from PHTN for physical activities with risk of fall or blunt abdominal trauma.
Prospective Incidence of Paediatric Inflammatory Bowel Disease in New Zealand in 2015
Authors: Lopez Robert N. , Evans Helen M. , Appleton Laura , Bishop Jonathan , Chin Simon , Mouat Stephen , Gearry Richard B. , Day Andrew S.
Published: October 2017

Background:

The global incidence of paediatric inflammatory bowel disease (IBD) is increasing. Much of the evidence attesting to this has arisen from North America and Europe. There is a relative paucity of information on the epidemiology of paediatric IBD in the Southern Hemisphere. The present study aimed to document the prospectively collected incidence of paediatric IBD in New Zealand in 2015.

Methods:

All patients younger than 16 years of age and diagnosed with IBD in New Zealand between 1 January 2015 and 31 December 2015 were identified. Demographic and disease phenotypic details were collected and entered into a secure database. Age‐specific population data for New Zealand were obtained and national incidence rates for IBD and its subtypes were calculated.

Results:

The prospectively calculated incidence of paediatric IBD, Crohn disease, ulcerative colitis (UC), and IBD unclassified in New Zealand in 2015 were 5.2 (95% confidence interval 3.9–6.8), 3.5 (2.4–4.8), 1.0 (0.5–1.8), and 0.7 (0.3–1.4) per 100,000 children, respectively.

Conclusions:

Incidence rates of paediatric IBD in New Zealand are comparable to the highest rates published in the literature from Western Europe and North America. Ongoing prospective ascertainment of the incidence of paediatric IBD is required to better understand the environmental factors, which are accounting for this increase in disease burden.
Initial Pain Management in Pediatric Acute Pancreatitis
Authors: Grover Amit S. , Mitchell Paul D. , Manzi Shannon F. , Fox Victor L.
Published: October 2017

Nearly all patients with acute pancreatitis (AP) experience some degree of abdominal pain that is severe enough to prompt medical evaluation and necessitate analgesia. Effective analgesia is a priority in caring for such patients. Despite its importance, strategies for pain management in AP have been poorly studied, particularly in the field of pediatrics. Presently, no published data examine the management of pain because of AP in children at the time of initial presentation. Management approaches are often extrapolated from adult practice and based on anecdotal experience in the absence of objective data. The aim of our study was to examine the initial provision of analgesia to children who presented to a pediatric emergency department with AP.
High Incidence of Proteinuria in Children With Chronic Intestinal Failure Under Long‐term Parenteral Nutrition
Authors: Billing Heiko , Traunspurger Anna , Sturm Ekkehard , Busch Andreas
Published: October 2017

Long‐term home parenteral nutrition (LTPN) in children with chronic intestinal failure (CIF) is associated with renal complications such as fluid and electrolyte imbalances, nephrocalcinosis, nephrolithiasis, and chronic kidney disease (CKD). The etiology of CIF‐associated nephropathy is multifactorial. The aim of this study was to evaluate renal involvement under LTPN. In this study, 50 patients with CIF, median age 4.2 years (1.4–9.3; 23 girls) were included. Kidney involvement was a frequent finding in this study. CKD was present in 30% of patients without correlation with LTPN duration. Glomerular proteinuria was found in the majority of patients (76%), an important long‐term risk factor for the progression of CKD. Increased urinary α‐1 microglobulin was significantly associated with duration (years) of LTPN and was increased in patients with CKD.
Pharmacokinetics of Sucralose and Acesulfame‐Potassium in Breast Milk Following Ingestion of Diet Soda
Authors: Rother Kristina I. , Sylvetsky Allison C. , Walter Peter J. , Garraffo H. Martin , Fields David A.
Published: October 2017

Objective:

The aim of this study was to determine sucralose and acesulfame‐potassium (ace‐K) pharmacokinetics in breast milk following maternal ingestion of a diet soda.

Methods:

Thirty‐four exclusively breast‐feeding women (14 normal‐weight, 20 obese) consumed 12 ounces of Diet Rite Cola, sweetened with 68‐mg sucralose and 41‐mg ace‐K, before a standardized breakfast meal. Habitual non‐nutritional sweeteners intake was assessed via a diet questionnaire. Breast milk was collected from the same breast before beverage ingestion and hourly for 6 hours.

Results:

Owing to one mother having extremely high concentrations, peak sucralose and acesulfame‐potassium concentrations following ingestion of diet soda ranged from 4.0 to 7387.9 ng/mL (median peak 8.1 ng/mL) and 299.0 to 4764.2 ng/mL (median peak 945.3 ng/mL), respectively.

Conclusions:

Ace‐K and sucralose transfer into breast milk following ingestion of a diet soda. Future research should measure concentrations after repeated exposure and determine whether chronic ingestion of sucralose and acesulfame‐potassium via the breast milk has clinically relevant health consequences.
Exploring the Relationship Between Body Mass Index and Positive Symptom Severity in Persons at Clinical High Risk for Psychosis
Authors: Caravaggio Fernando , Brucato Gary , Kegeles Lawrence S. , Lehembre-Shiah Eugénie , Arndt Leigh Y. , Colibazzi Tiziano , Girgis Ragy
Published: October 2017

Metabolic health and positive symptom severity has been investigated in schizophrenia, but not in clinical high risk (CHR) patients. We hypothesized that greater body mass index (BMI) in CHR patients would be related to less positive symptoms. We examined this relationship in CHR patients being treated with 1) no psychotropic medications (n = 58), 2) an antipsychotic (n = 14), or 3) an antidepressant without an antipsychotic (n = 10). We found no relationship between BMI and positive symptoms in unmedicated CHR patients, the majority of whom had a narrow BMI range between 20 and 30. However, in the smaller sample of CHR patients taking an antidepressant or antipsychotic, BMI was negatively correlated with positive symptoms. Although potentially underpowered, these preliminary findings provide initial steps in elucidating the relationships between metabolic health, neurochemistry, and symptom severity in CHR patients.
Safety and Efficacy of Theta-Burst Stimulation in the Treatment of Psychiatric Disorders
Authors: Rachid Fady
Published: October 2017

Theta-burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation and is thought to induce more rapid and longer-lasting effects on synaptic plasticity than conventional repetitive transcranial magnetic stimulation protocols. TBS is being used as an investigational and more recently as a therapeutic tool. The purpose of this review is to describe and discuss the studies that have evaluated the safety and efficacy of this technique in the treatment of various psychiatric disorders such as depression, schizophrenia, obsessive-compulsive disorder, Tourette's disorder, nicotine and cocaine addiction, and pathological gambling. Studies have reported mild adverse effects but no cases of seizures or mania. Despite the fact that studies were heterogeneous in terms of design and results, some of them are promising mostly for treatment-resistant depression and auditory hallucinations. Future well-designed sham-controlled studies are needed to confirm the long-term safety and efficacy of TBS in the treatment of such conditions.
Self-Harm, Affective Traits, and Psychosocial Functioning in Adults With Depressive and Bipolar Disorders
Authors: Weintraub Marc J. , Van de Loo Margaret M. , Gitlin Michael J. , Miklowitz David J.
Published: October 2017

Self-harm refers to the purposeful destruction of bodily tissue without suicidal intention and for purposes that are not socially sanctioned. Little is known about the associations between a history of self-harm, mood symptoms, and functioning in adults with different types of mood disorders. Lifetime histories of self-harm, current mood symptoms, global functioning, and affective traits were collected on 142 adults with mood disorders. The prevalence of lifetime self-harm was higher in patients with bipolar disorder compared with patients with a unipolar depressive disorder. Self-harm was also more strongly linked to impulsivity in individuals with bipolar disorder compared with unipolar depressive disorder. Across both diagnoses, histories of self-harm were related to lower levels of current global functioning, more severe depressive symptoms, and high self-reported emotional dysregulation and neuroticism. Findings indicate that self-harm is a potent prognostic variable for symptoms, global functioning, and personality functioning in individuals with mood disorders.
Evaluation of PD1/PDL1 Expression and Their Clinicopathologic Association in EBV-associated Lymphoproliferative Disorders in Nonimmunosuppressed Patients
Authors: Guo Ling , Bodo Juraj , Durkin Lisa , Hsi Eric D.
Published: October 2017

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD)/lymphomas in nonimmunosuppressed patients represent a unique entity and have been proposed to be related to immune senescence. Engagement of programmed cell death 1 (PD1) by its ligand programmed death ligand 1 (PDL1) inhibits T-cell activation, and leads to T-cell exhaustion. In clinical trials, therapeutic antibodies that block the PD1-PDL1 axis have shown promising therapeutic activity in certain types of lymphomas. Although PD1/PDL1 has been extensively studied in variety of lymphomas, there are few reports characterizing their expression in EBV-positive LPD. As these group of patients are presumed to be associated with immunosenescence/immune dysregulation, we hypothesize that the immune checkpoint pathway might be relevant in this entity. We explored the expression of PD1, PDL1 and its clinicopathologic association in 6 patients with a total of 8 independent specimens of EBV-positive LPD/lymphomas. We also applied proximity assay, a novel technique, which can identify intermolecular interaction, to evaluate physical interaction or in situ engagement of PD1 and PDL1. We found that the malignant cells in the EBV-positive LPDs express PDL1. PD1-positive tumor-infiltrating lymphocytes can be seen in these tumors. Proximity assay suggests there is active engagement between PD1 and PDL1. To our knowledge, this is the first report on the utility of proximity assay to test the active engagement between PD1 and PDL1 in lymphomas. As some EBV-positive LPDs were positive for PDL1, this subgroup of EBV-positive LPDs might be suitable for PD1/PDL1 antibody therapies.
Personalizing Gastric Cancer Screening With Predictive Modeling of Disease Progression Biomarkers
Authors: Walker Rachel , Mejia Jaime , Lee Jae K. , Pimiento Jose M. , Malafa Mokenge , Giuliano Anna R. , Coppola Domenico , Enderling Heiko
Published: October 2017

Gastric cancer (GC) remains the third most common cause of cancer-related death worldwide. Infection with Helicobacter pylori is responsible for over 70% of GC incidence; colonization induces chronic inflammation, which can facilitate progression to intestinal metaplasia, dysplasia, and GC (Correa pathway). Although H. pylori eradication is a necessary first step in GC prevention, some patients continue to progress to advanced stage disease if substantial tissue damage has occurred or inflammation persists. This progression is often asymptomatic until cancer reaches stage IV, yet efficient, cost-effective screening protocols for patients who present with early stages of the Correa pathway do not exist. Given the high interpatient heterogeneity in progression time through this pathway, such screening protocols must necessarily be personalized. This requires the identification of reliable and longitudinally assessable biomarkers of patient-specific progression. Several gastric stem cell (GSC) markers including CD44, CD133, and Lgr5 are upregulated in GC. Here we show a significant stepwise increase in immunohistochemical staining for these markers in biopsies at different stages of the Correa pathway, suggesting GSC fraction to be a promising candidate biomarker for early detection of malignant transformation. We present a mathematical model capable of both simulating clinically observed increases in GSC fraction in longitudinal biopsy samples of individual patients, and forecasting patient-specific disease progression trajectories based only on characteristics identified from immunohistochemistry at initial presentation. From these forecasts, personalized screening schedules may be identified that would allow early stratification of high-risk patients, and potentially earlier detection of dysplasia or early-stage GC.
Analysis of T1 Bladder Cancer on Biopsy and Transurethral Resection Specimens
Authors: Leivo Mariah Z. , Sahoo Debashis , Hamilton Zachary , Mirsadraei Leili , Shabaik Ahmed , Parsons John K. , Kader Andrew K. , Derweesh Ithaar , Kane Christopher , Hansel Donna E.
Published: October 2017

Urothelial carcinoma of the bladder invasive into lamina propria on biopsy or transurethral resection of bladder tumor, termed “T1” disease, progresses to muscularis propria invasion in a subset of patients. Prior studies have proposed histopathologic metrics to predict progression, although methods vary widely and it is unclear which method is most robust. This poses a challenge since recent World Health Organization and American Joint Commission on Cancer editions encourage some attempt to substratify T1 disease. To address this critical problem, we analyzed T1 specimens to test which T1 quantification method is best to predict progression and to then establish the optimal cut-off. Progression was analyzed for all patients or for patients with definitive muscularis propria only. Multivariate analysis and outcomes modeling controlled for additional histopathologic features. Our results suggest that aggregate linear length of invasive carcinoma (ALLICA) measured by optical micrometer is far superior to other methods (P=3.067×10−6) and could be applied to 100% of specimens. ALLICA retained significance in multivariate analysis and eliminated contribution of other histopathologic features to progression. The best cut-off for ALLICA using a 30% false-positive threshold was 2.3 mm and using a 10% false-positive threshold at 25 mm, although the latter severely limited patients who could achieve this threshold. After comparison of all proposed methods of T1 quantification, we recommend the adoption of the ALLICA measurement and a cut-off of ≥2.3 mm as the best predictor of progression, acknowledging that additional nonhistopathologic methods may be required to increase broad applicability and further reduce the false-positive threshold.
Olfactory Epithelial Hamartoma
Authors: Kossai Myriam , El Zein Sophie , Wassef Michel , Guichard Jean-Pierre , Pouliquen Christelle , Herman Philippe , Vérillaud Benjamin , Classe Marion
Published: October 2017

Sinonasal epithelial hamartomas occurring in adults are classified as seromucinous hamartoma (SMH) or respiratory epithelial adenomatoid hamartoma (REAH). We describe herein a novel subtype of adult sinonasal hamartoma that contains olfactory epithelium, a histologic feature not previously reported in the literature. Our pathology department database was retrospectively searched for sinonasal hamartomas containing areas of olfactory epithelium. Six relevant cases (3 male and 3 female patients; age, 30 to 77 y) were retrieved, and available pathology slides and clinical and imaging data from patient charts were reviewed. Five of the lesions were unilateral solitary, polypoid, pedunculated masses, 38 to 80 mm in length, lodged in the nasal olfactory cleft. The sixth lesion was associated with bilateral nasal polyposis, and its precise localization was not known. All patients were treated by transnasal endoscopic surgery. None of the 3 patients who had received adequate follow-up evaluation exhibited recurrence. Histologically, all lesions resembled SMH or REAH, with areas of olfactory epithelium comprising olfactory receptors and sustentacular and basal cells. Olfactory epithelium was observed at the lesion surface or in invaginated gland-like structures, and it contained focal aggregates of filamentous cell processes. Some olfactory receptor cells or cell processes were also present in the seromucinous gland component of lesions. Olfactory receptor cells expressed CD56 (neural cell adhesion molecule), and the filamentous aggregates contained CD56, neurofilaments, and synaptophysin. Aside from SMH and REAH, we have described a third subtype of adult sinonasal hamartoma—olfactory epithelial hamartoma—which shares the benign character of the other 2.
Loss of BAP1 Expression in Atypical Mesothelial Proliferations Helps to Predict Malignant Mesothelioma
Authors: Pillappa Raghavendra , Maleszewski Joseph J. , Sukov William R. , Bedroske Patrick P. , Greipp Patricia T. , Boland Jennifer M. , Yi Eunhee S. , Peikert Tobias , Aubry Marie Christine , Roden Anja C.
Published: October 2017

Distinguishing reactive mesothelial proliferation from malignant mesothelioma (MM) can be difficult, particularly on small biopsies. In this scenario, a diagnosis of atypical mesothelial proliferation might be rendered. However, the distinction between a reactive process and MM is important for prognosis and treatment. Recently, loss of BRCA1-associated protein 1 (BAP1) expression and/or homozygous deletion of CDKN2A were identified in some MM, but not in reactive mesothelial proliferations. We studied 34 cases of atypical mesothelial proliferation from our institutional files (1993 to 2016) for BAP1 expression, deletion of CDKN2A, and clinical outcome. Fifteen of 34 patients (44%) were subsequently diagnosed with MM. BAP1 expression was lost in 6 of these 15 (40%) patients. Ten of 15 (67%) patients died of disease within a median time of 18.2 months. BAP1 expression was also lost in 1 case of probable MM. In this case atypical mesothelial proliferation was identified in the pleura during a lobectomy procedure for lung adenocarcinoma. Follow-up of 57.0 months was remarkable for visceral and parietal pleural thickening with continued unilateral effusion identified on imaging studies but no subsequent definitive diagnosis of MM. CDKN2A studies by fluorescence in situ hybridization (performed in 31 cases) found no homozygous deletion of that gene in any case. In conclusion, loss of BAP1 expression in atypical mesothelial proliferation helps to predict MM and is a useful adjunct test in these cases. Homozygous deletion of CDKN2A in mesothelial cell proliferations did not prove to be useful to predict MM in cases of atypical mesothelial proliferation.
The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas
Authors: Skálová Alena , Stenman Göran , Simpson Roderick H.W. , Hellquist Henrik , Slouka David , Svoboda Tomas , Bishop Justin A. , Hunt Jennifer L. , Nibu Ken-Ichi , Rinaldo Alessandra , Vander Poorten Vincent , Devaney Kenneth O. , Steiner Petr , Ferlito Alfio
Published: October 2017

Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.
Clinical Targeted Next-Generation Sequencing Shows Increased Mutational Load in Endometrioid-type Endometrial Adenocarcinoma With Deficient DNA Mismatch Repair
Authors: Lee Paul J. , McNulty Samantha , Duncavage Eric J. , Heusel Jonathan W. , Hagemann Ian S.
Published: October 2017

A subset of endometrial adenocarcinomas (EACs) exhibit microsatellite instability and have deficient DNA mismatch repair (dMMR). The overall aim of the study was to compare the spectrum of mutations in endometrioid-type EAC with and without dMMR by using a clinically validated next-generation sequencing assay. We retrospectively identified 19 EACs with known mismatch repair status that had undergone targeted sequencing of a panel of cancer-related genes. The mismatch repair status was ascertained by immunohistochemistry against MLH1, PMS2, MSH2, and MSH6 mismatch proteins. Somatic mutations in EAC with dMMR were compared against those in cases with proficient MMR (pMMR). The dMMR EAC showed a normalized mean of 66.6 mutations/Mb per case compared with pMMR EAC with a mean of 26.2 (P<0.05). The most commonly mutated genes were PTEN (89% of dMMR, 50% of pMMR), PIK3CA (67% vs. 40%), ATM (89% vs. 40%), and FLT3 (67% vs. 50%). The transition/transversion ratio was 4.7 versus 2.8 for the dMMR and pMMR cohorts, respectively (P<0.05). Copy number variant analysis did not demonstrate significant differences between the dMMR and pMMR cohorts and was not correlated with histologic grade of EAC. In conclusion, tumorigenesis of EAC in the context of dMMR demonstrated heavier mutational burdens and higher transition/transversion ratio. The spectrum of genetic alterations can potentially help identify cases with microsatellite instability phenotype using next-generation sequencing data from a targeted cancer gene panel.
Implementation of a 5-Minute Magnetic Resonance Imaging Screening Protocol for Prostate Cancer in Men With Elevated Prostate-Specific Antigen Before Biopsy
Authors: Weiss Jakob , Martirosian Petros , Notohamiprodjo Mike , Kaufmann Sascha , Othman Ahmed E. , Grosse Ulrich , Nikolaou Konstantin , Gatidis Sergios
Published: October 2017

Purpose

The aims of this study were to establish a 5-minute magnetic resonance (MR) screening protocol for prostate cancer in men before biopsy and to evaluate effects on Prostate Imaging Reporting and Data System (PI-RADS) V2 scoring in comparison to a conventional, fully diagnostic multiparametric MR imaging (mpMRI) approach.

Materials and Methods

Fifty-two patients with elevated prostate-specific antigen levels and without prior biopsy were prospectively included in this institutional review board–approved study. In all patients, an mpMRI protocol according to the PI-RADS recommendations was acquired on a 3 T MRI system. In addition, an accelerated diffusion-weighted imaging sequence was acquired using simultaneous multislice technique (DW-EPISMS). Two readers independently evaluated the images for the presence/absence of prostate cancer according to the PI-RADS criteria and for additional findings. In a first reading session, only the screening protocol consisting of axial T2-weighted and DW-EPISMS images was made available. In a subsequent reading session, the mpMRI protocol was assessed blinded to the results of the first reading, serving as reference standard.

Results

Both readers successfully established a final diagnosis according to the PI-RADS criteria in the screening and mpMRI protocol. Mean lesion size was 1.2 cm in the screening and 1.4 cm in the mpMRI protocol (P = 0.4) with 35% (18/52) of PI-RADS IV/V lesions. Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100% for both readers with no significant differences in comparison to the mpMRI standard (P = 1.0). In 3 patients, suspicious lymph nodes were reported as additional finding, which were equally detectable in the screening and mpMRI protocol.

Conclusions

A 5-minute MR screening protocol for prostate cancer in men with elevated prostate-specific antigen levels before biopsy is applicable for clinical routine with similar diagnostic performance as the full diagnostic mpMRI approach.
Complications From Surgically Assisted Rapid Maxillary Expansion With HAAS and HYRAX Expanders
Authors: Pereira Max Domingues , Koga Alexandre Fukuzo , Prado Gabriela Pereira Ribeiro , Ferreira Lydia Masako
Published: October 2017

The current study aimed at comparing the number and type of undesired outcomes during and after the maxillary expansion performed with HYRAX and HAAS expanders. A total of 90 patients (41 males and 49 females, 45.6% and 54.4%, respectively) aged 18 to 59 (mean age of 26.1; standard deviation [SD] = 7.4) underwent subtotal Le Fort I osteotomy and pterygomaxillary disjunction following surgically assisted rapid maxillary expansion (SARME) carried out using HAAS (n = 29; 48.3% male and 51.7% female; mean age = 27: SD = 7.7) and HYRAX (n = 61; 44.3% male and 55.7% female; mean age = 26; SD = 7.2) expanders. Post-SARME dento-gingival, radiographic, and clinical undesired outcomes were evaluated. A total of 16 (17.8%) patients experienced at least 1 undesired outcome—7 (7.8%) and 9 (10.0%) in HAAS and HYRAX group, respectively. The most common undesired outcomes were radiographic asymmetric expansion—2 (2.2%) and 3 (3.3%) in HAAS and HYRAX group, respectively—followed by pain during out-of-clinic expansion 4 (4.4%) in HAAS group only—dental darkening 5 (5.5%) in HYRAX group, only, requiring root canal treatment, and local infection—2 (2.2%), 1 in each HAAS and HYRAX groups. Excepting for complications arising from the acrylic stop plate in HAAS expander, the number and severity of complications observed in the current study did not differ due to the use of HAAS and HYRAX appliances to perform maxillary expansion. Hygiene issues do not rule out the use of HAAS. The wider maxillary expansion performed, the more frequent are the cases of asymmetric expansion.
The Impact of Type-D Personality on Oral Health-Related Quality of Life in Cleft Lip and Palate Adolescents
Authors: Ajami Shabnam , Toraby Farzaneh , Shavakhi Mojgan , Eslami Neda
Published: October 2017

The purpose of this study was to investigate the oral health-related quality of life and type-D personality in cleft lip/palate (CLP) patients and the relationship between type-D personality and oral health-related quality of life (OHRQoL) in CLP patients. Fifty patients with CLP within age range from 8 to 15 years were chosen and asked to complete both Child Oral Health Impact Profile (COHI) and Type-D scale (DS14) questionnaire. Moreover, the participants of a control group matched with CLP patients were asked to complete the DS14 questionnaire. A significant difference between boys and girls on the subscale “emotional well-being” of COHIP (P= 0.001) and a positive significant correlation between “oral symptoms” and age (P= 0.029) were found among CLP patients. The prevalence of type-D personality was equal between clefts and nonclefts groups. However, there was a significant relationship between type-D personality and OHRQoL in CLP patients regarding mean scores of overall COHIP and its subscales (P< 0.05). This study has shown that the personality type remains unchanged among cleft patients and a meaningful relationship exists between type-D personality and OHRQoL.
Accessory Mental Foramen and Maxillofacial Surgery
Authors: Rahpeyma Amin , Khajehahmadi Saeedeh
Published: October 2017

Accessory mental foramens should be considered in surgical procedures performed in mandibular body and symphysis. Location and content of these foramina has significant impact on the result of surgery.

Lip numbness is the catastrophic result if these foramina are violated while their content is nerves that carry sensory inputs from lower lip. Examples of interferences with dental implant, orthognathic, and periapical surgeries are presented and it is discussed in which conditions they complicate oral surgical procedures.
Timed Up and Go Test Performance as an Indicator of Fall History in Institutionalized Elderly
Authors: Millán-Calenti José C. , Núñez-Naveira Laura , Lorenzo-López Laura , Rodríguez-Villamil José L. , Muñoz-Mendoza Carmen L. , Cabañero-Martínez M. José , Cabrero-García Julio , Maseda Ana
Published: October 2017

Background:

Ageing is associated with sensory and physical declines and falling risk.

Objective:

To determine the association between 3 performance-based mobility tests and fall history.

Methods:

Fifty participants' mobility was assessed by Timed Up and Go (TUG) and 4- and 6-m walking tests (WT).

Results:

The TUG performance correlated with 4- and 6-m WT performance, and performance on 4-m WT positively correlated with 6-m WT. Only TUG performance showed a strong relationship to fall history.

Conclusions:

Performance tests could indicate the presence of fall history in the institutionalized older adults; the TUG being the most suitable compared with other common WT.