Integration and usability of a digital cancer risk stratification tool to optimize identification of patients at risk for hereditary cancers: A pilot study.

BACKGROUND: Patients with a personal or family history of cancer may have elevated risk of developing future cancers, which often remains unrecognized due to lapses in screening. This pilot study assessed the usability and clinical outcomes of a cancer risk stratification tool in a gynecologic oncology clinic. METHODS: New gynecologic oncology patients were prompted to complete a commercially developed personal and family history-based risk stratification tool to assess eligibility for genetic testing using National Comprehensive Cancer Network criteria and estimated lifetime breast cancer risk using the Tyrer-Cuzick model. After use of the risk stratification tool, usability was assessed via completion rate and the System Usability Scale, and health literacy was assessed using the BRIEF Health Literacy Screening Tool. RESULTS: 130 patients were prompted to complete the risk stratification tool; 93 (72%) completed the tool. Race and ethnicity and insurance type were not associated with tool completion. The median System Usability Scale score was 83 out of 100 (interquartile range, 60-95). Health literacy positively correlated with perceived usability. Public insurance and race or ethnicity other than non-Hispanic White was associated with lower perceived usability. Sixty (65%) patients met eligibility criteria for genetic testing, and 21 (38% of 56 eligible patients) were candidates for enhanced breast cancer screening based on an estimated lifetime breast cancer risk of ≥20%. CONCLUSIONS: A majority of patients completed the digital cancer risk stratification tool. Older age, lower health literacy, public insurance, and race or ethnicity other than non-Hispanic White were associated with lower perceived tool usability.

Effect of Slow and Deep Breathing on Brain Waves in Regular Yoga Practitioners.

Various yogic practices focus on breathing. Breathing may affect brain waves. This cross-sectional study was conducted to see the effect slow and deep respiration on EEG activity in experienced Yoga practitioners at the Department of Physiology at AIIMS, Bhopal, India. The duration of the study was about one year. EEG was taken and was analyzed by Dinamika - Advanced Test System, Moscow, Russia. Paired t-test using graph pad software was used for statistical analysis. The Delta percentage decreased and the other wave's percentages theta, alpha, and beta increased significantly. The person becomes deeply relaxed and more focussed on slow and deep breathing.

Management of cyclic vomiting syndrome in adults: Evidence review.

BACKGROUND: This evidence review was conducted to inform the accompanying clinical practice guideline on the management of cyclic vomiting syndrome (CVS) in adults. METHODS: We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and focused on interventions aimed at prophylactic management and abortive treatment of adults with CVS. Specifically, this evidence review addresses the following clinical questions: (a) Should the following pharmacologic agents be used for prophylaxis of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, or mitochondrial supplements? (b) Should the following pharmacologic agents be used for abortive treatment: triptans or aprepitant? RESULTS: We found very low-quality evidence to support the use of the following agents for prophylactic and abortive treatment of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, and mitochondrial supplements. We have moderate certainty of evidence for the use of triptans as abortive therapy. We found limited evidence to support the use of ondansetron and the treatment of co-morbid conditions and complementary therapies. CONCLUSIONS: This evidence review helps inform the accompanying guideline for the management of adults with CVS which is aimed at helping clinicians, patients, and policymakers, and should improve patient outcomes.

Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association.

The increasing recognition of cyclic vomiting syndrome (CVS) in adults prompted the development of these evidence-based guidelines on the management of CVS in adults, which was sponsored by the American Neurogastroenterology and Motility Society (ANMS) and the Cyclic Vomiting Syndrome Association (CVSA). GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework was used and a professional librarian performed the literature search. The expert committee included the President of the CVSA who brought a patient perspective into the deliberations. The committee makes recommendations for the prophylaxis of CVS, treatment of acute attacks, diagnosis, and overall management of CVS. The committee strongly  recommends that adults with moderate-to-severe CVS receive a tricyclic antidepressant (TCA), such as amitriptyline, as a first-line prophylactic medication and receive topiramate or aprepitant as alternate prophylactic medications. Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L-carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications. For acute attacks, the committee conditionally recommends using serotonin antagonists, such as ondansetron, and/or triptans, such as sumatriptan or aprepitant to abort symptoms. Emergency department treatment is best achieved with the use of an individualized treatment protocol and shared with the care team (example provided). The committee recommended screening and treatment for comorbid conditions such as anxiety, depression, migraine headache, autonomic dysfunction, sleep disorders, and substance use with referral to appropriate allied health services as indicated. Techniques like meditation, relaxation, and biofeedback may be offered as complementary therapy to improve overall well-being and patient care outcomes.

Effect of preoperative inspiratory muscle training on physical functioning following esophagectomy.

This study aims to examine the effect of preoperative inspiratory muscle training (IMT) on pre- and postoperative functional exercise performance in patients undergoing esophagectomy. A subcohort of patients recruited to the PREPARE randomized control trial were studied. Following evaluation of respiratory muscle function (spirometry, maximum inspiratory pressure (MIP), and inspiratory muscle endurance), postoperative mobilization (accelerometry) and postoperative physical functioning (6-minute walk test (6MWT)), participants scheduled for esophagectomy were randomly assigned to either 2 weeks of preoperative IMT or a control group. Measures were repeated on the day before surgery and postoperatively. Sixty participants (mean (standard deviation) age 64.13 (7.8) years; n = 42 male; n = 43 transthoracic esophagectomy; n = 17 transhiatial esophagectomy) were included in the final analysis (n = 28 IMT; n = 32 control). There was a significant improvement in preoperative MIP (P = 0.03) and inspiratory muscle endurance (P = 0.04); however preoperative 6MWT distance did not change. Postoperatively, control participants were more active on postoperative day (POD)1, and from POD1-POD5 (P = 0.04). Predischarge, 6MWT distance was significantly lower in the IMT group (305.61 (116.3) m) compared to controls (380.2 (47.1) m, P = 0.03). Despite an increase in preoperative respiratory muscle function, preoperative IMT does not improve pre- or postoperative physical functioning or postoperative mobilization following esophagectomy.

Cortical Processing of Frequency Changes Reflected by the Acoustic Change Complex in Adult Cochlear Implant Users.

The purpose of this study was to examine neural substrates of frequency change detection in cochlear implant (CI) recipients using the acoustic change complex (ACC), a type of cortical auditory evoked potential elicited by acoustic changes in an ongoing stimulus. A psychoacoustic test and electroencephalographic recording were administered in 12 postlingually deafened adult CI users. The stimuli were pure tones containing different magnitudes of upward frequency changes. Results showed that the frequency change detection threshold (FCDT) was 3.79% in the CI users, with a large variability. The ACC N1' latency was significantly correlated with the FCDT and the clinically collected speech perception score. The results suggested that the ACC evoked by frequency changes can serve as a useful objective tool in assessing frequency change detection capability and predicting speech perception performance in CI users.

Preliminary Outcomes Report for CO2 Laser Assisted Electric-Acoustic Cochlear Implantation.

OBJECTIVE: Report on the safety/efficacy of a novel, carbon dioxide (CO2) laser-assisted protocol for hearing-preservation cochlear implantation (HPCI) and electric-acoustic stimulation (EAS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Adult patients meeting established criteria for HPCI and EAS. INTERVENTION: Therapeutic/rehabilitative. A standardized protocol used CO2 laser to achieve meticulous hemostasis and perform cochleostomy was evaluated. MAIN OUTCOME MEASURES: Audiometric assessments included low-tone pure tone average (LtPTA), consonant-nucleus-consonant (CNC), and AzBio scores. Primary outcomes were low-tone hearing-preservation (LtHP) and EAS usage rates. Secondary outcomes included change in LtPTA, outcomes durability, and the rate/onset/presentation of delayed hearing loss (DHL). Subset analyses stratified data by presenting LtPTA and surgeon experience. RESULTS: Forty-seven patients and 52 ears were included. Mean follow-up was 20.7 ±â€Š12.6 months. When adjusted for preoperative LtPTA less than 60 dB, the LtHP rate was 77%. This was significantly better than for patients with LtPTA more than 60 dB (24%; p < 0.0001). Outcomes were highly durable. EAS usage was excellent in those with LtPTA less than 60 dB (100%). Nine patients developed DHL. Three additional patients (25%) were successfully salvaged via steroids. Both CNC and AzBio scores improved significantly (p < 0.0001) at definitive testing. Speech-hearing scores did not differ significantly between patients using/not using EAS. The complication rate was 3.8%; none were caused by the laser. Surgeon experience was associated with significantly better outcomes. CONCLUSION: Use of a CO2 laser-assisted HPCI protocol was safe and effective. Outcomes were consistent with contemporary literature reporting. Patient selection and surgeon experience both significantly impacted outcomes.

Transinguinal interstitial (intranodal) lymphatic embolization to treat high-output postoperative lymphocele.

Postoperative lymphoceles may occur after abdominal or pelvic surgery secondary to disruption of lymphatic channels. First-line therapy includes conservative therapy with medical management and dietary restriction. Despite these measures, some patients may have persistent high-output lymphoceles requiring percutaneous aspiration, drainage, or sclerosis. Rarely, surgical evacuation is required. Management of intrathoracic chyle leak by thoracic duct embolization has been well described. Recently, interstitial (intranodal) lymphatic embolization for the treatment of plastic bronchitis has been performed. This case report describes interstitial (intranodal) lymphatic embolization as a novel therapy for high-output postoperative pelvic lymphocele.

Metabolic targeting of HIF-dependent glycolysis reduces lactate, increases oxygen consumption and enhances response to high-dose single-fraction radiotherapy in hypoxic solid tumors.

BACKGROUND: A high rate of glycolysis leading to elevated lactate content has been linked to poor clinical outcomes in patients with head and neck and cervical cancer treated with radiotherapy. Although the biological explanation for this relationship between lactate and treatment response remains unclear, there is a continued interest in evaluating strategies of targeting metabolism to enhance the effectiveness of radiotherapy. The goal of this study was to investigate the effect of metabolic-targeting through HIF-1α inhibition and the associated changes in glycolysis, oxygen consumption and response on the efficacy of high-dose single-fraction radiotherapy (HD-SFRT). METHODS: HIF-1α wild-type and HIF-1α knockdown FaDu and ME180 xenograft tumors were grown in the hind leg of mice that were placed in an environmental chamber and exposed to different oxygen conditions (air-breathing and hypoxia). Ex vivo bioluminescence microscopy was used to measure lactate and ATP levels and the hypoxic fraction was measured using EF5 immunohistochemical staining. The oxygen consumption rate (OCR) in each cell line in response to in vitro hypoxia was measured using an extracellular flux analyzer. Tumor growth delay in vivo was measured following HD-SFRT irradiation of 20 Gy. RESULTS: Targeting HIF-1α reduced lactate content, and increased both oxygen consumption and hypoxic fraction in these tumors after exposure to short-term continuous hypoxia. Tumors with intact HIF-1α subjected to HD-SFRT immediately following hypoxia exposure were less responsive to treatment than tumors without functional HIF-1α, and tumors irradiated under air breathing conditions regardless of HIF-1α status. CONCLUSIONS: Blocking the HIF1 response during transient hypoxic stress increased hypoxia, reduced lactate levels and enhanced response to HD-SFRT. This strategy of combining hypofractionated radiotherapy with metabolic reprogramming to inhibit anaerobic metabolism may increase the efficacy of HD-SFRT through increased oxygen consumption and complementary killing of radiosensitive and hypoxic, radioresistant cells.

Outcomes in gastric and junctional cancer using neoadjuvant and adjuvant chemotherapy (epirubicin, oxaliplatin, and capecitabine) and radical surgery.

BACKGROUND: The MAGIC/UK Medical Research Council (MRC) trial set the standard of care for treatment of resectable gastric and junctional adenocarcinoma, demonstrating that perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (ECF) confers a survival benefit over surgery alone. The randomized ECF for advanced and locally advanced esophagogastric cancer (REAL-2) trial showed that, in the metastatic setting, the EOX regimen (epirubicin, oxaliplatin and capecitabine) is as effective as ECF, with a favourable toxicity profile. METHODS: Consecutive patients with resectable gastric or junctional adenocarcinoma treated with perioperative EOX, between 2007 and 2012, were retrospectively analysed. RESULTS: Fifty-nine patients (12 female, 47 male), commenced EOX therapy; 47 underwent surgery. A good pathological response was seen in 34%, (16/47). Disease recurrence occurred in 19 patients (19/47, 40%). Median overall survival was 22 months, with 4-year survival of 47%. Chemotoxicities were consistent with those previously reported for this regimen. CONCLUSION: This study in a high-volume centre demonstrates that EOX in resectable gastric and junctional adenocarcinoma is associated with a reasonable safety profile, and efficacy consistent with that reported for ECF.

The resistance of breast cancer stem cells to conventional hyperthermia and their sensitivity to nanoparticle-mediated photothermal therapy.

Breast tumors contain a small population of tumor initiating stem-like cells, termed breast cancer stem cells (BCSCs). These cells, which are refractory to chemotherapy and radiotherapy, are thought to persist following treatment and drive tumor recurrence. We examined whether BCSCs are similarly resistant to hyperthermic therapy, and whether nanoparticles could be used to overcome this resistance. Using a model of triple-negative breast cancer stem cells, we show that BCSCs are markedly resistant to traditional hyperthermia and become enriched in the surviving cell population following treatment. In contrast, BCSCs are sensitive to nanotube-mediated thermal treatment and lose their long-term proliferative capacity after nanotube-mediated thermal therapy. Moreover, use of this therapy in vivo promotes complete tumor regression and long-term survival of mice bearing cancer stem cell-driven breast tumors. Mechanistically, nanotube thermal therapy promotes rapid membrane permeabilization and necrosis of BCSCs. These data suggest that nanotube-mediated thermal treatment can simultaneously eliminate both the differentiated cells that constitute the bulk of a tumor and the BCSCs that drive tumor growth and recurrence.

Radiographic anatomy of the infracochlear approach to the petrous apex for computer-assisted surgery.

OBJECTIVE: 1) To define the surgical anatomy and dimensions of the infracochlear approach to the petrous apex through the use of high-resolution computed tomography and 2) use of digitized images of cadaveric temporal bones for computer simulation of infracochlear access using the Ohio Supercomputer Center/Ohio State University temporal bone simulator. BACKGROUND: The petrous apex is a surgically challenging area to access. Many routes have been described and used successfully in clinical practice. However, these routes have not been defined with the aim of application in computer-assisted surgery. The infracochlear approach, due to its access via a transcanal route, affords the opportunity for its potential application in minimally invasive computer-assisted surgery. METHODS: High-resolution computed tomographic scans were performed on 102 cadaveric skulls (204 temporal bones). Standard measurements were taken using an open-source picture archiving and communication system software of the maximum height, width, and depth of the infracochlear approach. In addition, the maximum diameter of a circular fenestration that could be created in the infracochlear space without breaching the basal turn of the cochlea, internal carotid artery, or the jugular bulb was used to simulate a drill path. In addition, 5 temporal bone specimens (3 left, 2 right) underwent high-resolution computed tomography, with the digitized images being used to create simulated temporal bones for infracochlear surgical access; the transcanal infracochlear approach was then performed by the same surgeon on the cadaveric bone. RESULTS: The mean height, width, and depth of the infracochlear space in temporal bones with nonpneumatized petrous apices were 7.2 +/- 0.4, 9.4 +/- 0.8, and 17.5 +/- 1.0 mm, respectively. Corresponding dimensions in pneumatized petrous apices were 7.6 +/- 0.4, 10.1 +/- 1.1, and 18.6 +/- 0.8 mm, respectively. The mean diameter of the circular fenestra in the nonpneumatized petrous apices was 5.1 +/- 0.4 compared with 5.7 +/- 0.6 mm in pneumatized petrous pieces. This was statistically significant (unpaired t test; p value = 0.04). The time to perform a simulated infracochlear approach to the petrous apex ranged from 3.1 to 12.6 minutes (mean, 6.1 minutes). The time to perform the same approach on the cadaveric bone ranged from 4.32 to 14.1 minutes (mean, 9.3 minutes). CONCLUSION: Temporal bones with pneumatized petrous apices have an overall larger infracochlear space. The mean diameter of a circular infracochlear path that would avoid damage to vital structures was sufficiently large in both pneumatized and nonpneumatized petrous apices to have a potential application as a safe approach in computer-assisted surgery. Such an application is feasible with mating of a robotic system with computed tomographic- or magnetic resonance imaging-guided imagery, which is the next phase of this study.

Effectiveness of pulsed dye laser in the treatment of recalcitrant warts in children.

BACKGROUND: To determine the efficacy and safety of the 585-nm pulsed dye laser (PDL) in the treatment of recalcitrant warts in children. METHODS AND MATERIAL: Retrospective survey of the medical records of children with recalcitrant warts who were treated with PDL between March 1995 through January 1999 at the Children's Memorial Hospital outpatient subspecialty center, Chicago, Illinois. RESULTS: Sixty-one children with recalcitrant warts were treated with PDL; 75% of them had total clearance of warts after an average of 3.1 treatment sessions. Overall success rates were 100% for both perineal and perianal and face-only warts, 93% for hands, 69% for plantar warts, 67% when both face and extremities were involved, and 60% when multiple extremities were involved. Pain and other side effects were minimal. Mild scarring occurred in 2% of patients; 75% of patients remained free of warts after a follow-up period of 24 months or longer. CONCLUSION: PDL therapy is an effective, safe alternative therapy for treatment of recalcitrant warts in children, with few side effects and a low long-term recurrence rate.

Pilot translational study of dietary vitamin C supplementation in Barrett's esophagus.

The transcription factor Nuclear factor kappa B (NF-kappaB) is central to the regulation of genes encoding for mediators of inflammation and carcinogenesis. In the esophagus, NF-kappaB is progressively activated from inflammation to Barrett's metaplasia and adenocarcinoma. Vitamin C, an antioxidant, can inhibit NF-kappaB in in vitro models, and the aim of this study was to prospectively assess the effect of supplemental vitamin C on NF-kappaB and associated cytokines in patients with Barrett's esophagus. Twenty-five patients with long-segment Barrett's and specialized intestinal metaplasia received dietary vitamin C (1000 mg/day) orally for four weeks, and had pre- and post-vitamin C endoscopic biopsies. NF-kappaB activity (activated p50 and p65 subunits) of nuclear extracts was assessed using the Active Motif NF-kappaB assay, and cytokines and growth factors were measured using the Evidence Investigator biochip array. NF-kappaB and related pro-inflammatory cytokines and growth factors (IL-8, VEGF, IL-10) were activated in all Barrett's tissue pre-treatment. Down-regulation in activated NF-kappaB and cytokines was observed in 8/25 (35%) patients. Dietary vitamin C supplementation may down-regulate pro-inflammatory markers in a subset of Barrett's patients. Further studies with larger numbers of endpoints will be needed to further evaluate this effect.

Recovery function of the late auditory evoked potential in cochlear implant users and normal-hearing listeners.

BACKGROUND: It has been theorized that neural recovery is related to temporal coding of speech sounds. The recovery function of cortically generated auditory evoked potentials has not been investigated in cochlear implant (CI) users. PURPOSE: This study characterized the recovery function of the late auditory evoked potential (LAEP) using a masker-probe paradigm in postlingually deafened adult CI users and young normal-hearing (NH) listeners. RESEARCH DESIGN: A case-control study of the late auditory evoked potentials using electrophysiological technique was performed. The LAEP was evoked by 1 kHz tone bursts presented in pairs, with the first stimuli as the maskers and the second stimuli as the probes. The masker-probe intervals (MPIs) were varied at 0.7, 1, 2, 4, and 8 sec, with an interpair interval of 12 sec. STUDY SAMPLE: Nine CI users and nine NH listeners participated in this study. DATA COLLECTION AND ANALYSIS: The normalized amplitude from the probe response relative to the masker response was plotted as a function of the MPI to form a recovery function. The latency shift for the probe response relative to the masker response was calculated. RESULTS: The recovery function was approximately linear in log scale of the MPI in NH listeners, while it showed somewhat different recovery patterns with a large intersubject variability in CI users. Specifically, although the probe response was approximately 60 percent of the masker response for the MPI of 0.7 sec in both groups, the recovery function of CI users displayed a nonlinear pattern, with a steeper slope than that of NH listeners. The probe response completely recovered at the MPI of 4 sec in NH listeners and at the MPI of 2 sec in CI users. N1 and P2 latencies from probe responses were shorter than those from masker responses in NH listeners, while no latency difference was found between probe responses and masker responses in CI users. CONCLUSIONS: Our interpretation of these findings is that the faster recovery of the LAEP in CI users is related to abnormal adaptation mechanisms and a less prominent role of the components with longer latencies in the LAEP of CI users. Other mechanisms such as the compromised inhibitory regulation in the auditory system and the aging effect in CI users might also play a role. More research needs to be done to determine whether the slope of the LAEP recovery function is correlated with speech-perception performance.