Input-Output Functions in Human Heads Obtained With Cochlear Implant and Transcranial Electric Stimulation.

OBJECTIVES: Electric stimulation is used to treat a number of neurologic disorders such as epilepsy and depression. However, delivering the required current to far-field neural targets is often ineffective because of current spread through low-impedance pathways. Here, the specific aims are to develop an empirical measure for current passing through the human head and to optimize stimulation strategies for targeting deeper structures, including the auditory nerve, by utilizing the cochlear implant (CI). MATERIALS AND METHODS: Outward input/output (I/O) functions were obtained by CI stimulation and recording scalp potentials in five CI subjects. Conversely, inward I/O functions were obtained by noninvasive transcranial electric stimulation (tES) and recording intracochlear potentials using the onboard recording capability of the CI. RESULTS: I/O measures indicate substantial current spread, with a maximum of 2.2% gain recorded at the inner ear target during tES (mastoid-to-mastoid electrode configuration). Similarly, CI stimulation produced a maximum of 1.1% gain at the scalp electrode nearest the CI return electrode. Gain varied with electrode montage according to a point source model that accounted for distances between the stimulating and recording electrodes. Within the same electrode montages, current gain patterns varied across subjects suggesting the importance of tissue properties, geometry, and electrode positioning. CONCLUSION: These results provide a novel objective measure of electric stimulation in the human head, which can help to optimize stimulation parameters that improve neural excitation of deep structures by reducing the influence of current spread. CONFLICT OF INTEREST: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Cutaneous leiomyosarcoma: dermal and subcutaneous.

BACKGROUND AND OBJECTIVES: Leiomyosarcoma of skin (LMS) can be sub-classified on pathology appearances as Dermal or Subcutaneous. The aim of this study was to provide treatment recommendations for these uncommon tumours. METHODS: A retrospective review of all patients with dermal and subcutaneous leiomyosarcoma managed at the Peter MacCallum Cancer Centre, Australia from January 2003 to December 2018 was performed. Eighty-three patients were identified (64 dermal leiomyosarcoma, 19 subcutaneous leiomyosarcoma). RESULTS: Subcutaneous leiomyosarcoma were larger (median size 14 mm dermal, 49 mm subcutaneous, P = 0.01). No patient with a dermal leiomyosarcoma developed metastatic disease compared to 4 of the 19 subcutaneous leiomyosarcoma (5-year overall survivals, 98% and 88%, respectively, P = 0.03). The most common site of metastasis was to the lung. No difference in risk of local recurrence was apparent (5-year recurrence-free survivals were 85% and 78%, respectively, P = 0.17). Adjuvant radiotherapy was used in 16 (25%) dermal leiomyosarcoma patients and 13 (68%) subcutaneous leiomyosarcoma patients (P < 0.001). Local recurrence was uncommon in both tumour subtypes when patients received definitive surgical excision (minimum histological margins of 10 mm as per institutional protocol) regardless of whether radiotherapy was used. The 5-year local recurrence-free survival for dermal leiomyosarcoma treated with radiotherapy was 93% versus 83% without radiotherapy (P = 0.7) and for subcutaneous leiomyosarcoma was 69% and 100%, respectively (P = 0.9). CONCLUSIONS: Dermal leiomyosarcoma have an excellent prognosis, particularly after definitive surgical excision with margins of at least 10 mm. Subcutaneous leiomyosarcoma has poorer outcomes and should be managed by wider excision and considered for adjuvant radiotherapy.

Cytotoxic effects of heated tobacco products (HTP) on human bronchial epithelial cells.

BACKGROUND: Heated tobacco product(s) (HTP), also called heat-not-burn products, are a re-emerging class of tobacco products that purport to reduce health risk compared with smoking combustible tobacco products. This study examined the potential toxic effects of inhaling emissions from an HTP in comparison with electronic and combustible tobacco cigarettes. METHODS: Inhalation toxicity of HTP (IQOS; tobacco flavour), e-cigarette (MarkTen; tobacco flavour) and tobacco cigarette (Marlboro Red) was examined in vitro using an air-liquid interface with human bronchial epithelial cells (H292). Cells were exposed directly to 55 puffs from the e-cigarette, 12 puffs from the HTP and 8 puffs from the tobacco cigarette to equilibrate nicotine delivery to the cells across products. Cytotoxicity was measured using neutral red uptake and trypan blue assays. Cytotoxic effects of each tested product (HTP, e-cigarette and tobacco cigarette) were compared with an air control. Release of inflammatory markers (cytokines) was measured using ELISA. RESULTS: The HTP showed higher cytotoxicity compared with the air controls using the neutral red assay. The HTP also showed higher cytotoxicity than the e-cigarette, but lower cytotoxicity than the combustible cigarettes using the same assay. A significant increase in cytokines levels, compared with air controls, was observed postexposure to tobacco smoke but not to emissions from HTP or e-cigarette aerosol. DISCUSSION: Using limited cytotoxic measures, the HTP showed reduced cytotoxicity relative to a combustible cigarette but higher toxicity than an e-cigarette. More comprehensive testing is needed to determine long-term effects of inhaling emissions from HTP.

Retrospective audit of patients referred for further treatment following Mohs surgery for non-melanoma skin cancer.

BACKGROUND/OBJECTIVES: To describe the characteristics, subsequent management and outcomes of patients referred for further management following Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: Retrospective analysis of patients referred to a quaternary cancer centre from 2000 to 2015. RESULTS: In total, 83 lesions in 82 patients were referred for further management; 52 (62%) were SCC and 80 (96%) were located in the head and neck. Reasons for referral included high-risk disease for consideration for adjuvant radiotherapy (37/83, 45%), inadequate resection (28/83, 34%) or recurrence following previous MMS (15/83, 17%). Fewer than 40% of the 69 referrals received from MMS surgeons included photos or an operative report and diagram. There was discordance in pathology opinion in 11 (13%) of cases. Histopathology from MMS was reviewed in eight cases and there was discordance with the in-hospital pathology opinion in six of these. In-hospital re-excision was performed in 19 cases and in five of these the pathology report on the paraffin-sectioned re-excised tissue was discordant with prior MMS assessment. Significantly, two cases were associated with a misinterpretation of lymphocytic infiltrate as residual disease in patients with chronic lymphocytic leukaemia (CLL). CONCLUSION: This study highlights some of the challenges and limitations of MMS. Early referral for multidisciplinary management is recommended when MMS resection margins are inadequate or uncertain, especially for high-risk SCC. We recommend that referrals be accompanied by histological material, as well as a detailed report with operative photos and diagrams. CLL can pose an intraoperative diagnostic challenge. Discrepancies in the interpretation of MMS slides present an opportunity for improvement, and our findings support the role of ongoing quality assurance programs.

Impact of advancing age on treatment and outcomes in anal cancer.

BACKGROUND: Chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCCA) may cause significant toxicity, and concerns exist about its tolerability in the elderly. The authors compared tolerability and outcomes across the age groups following CRT for SCCA. METHODS: Single-institution retrospective analysis of patients with localized SCCA treated with CRT. CRT was standardized at 50.4-54 Gy, with concurrent infusional 5-fluorouracil and mitomycin C. Patients were arbitrarily categorized into three groups: Group 1 - age < 50 years; Group 2 - age ≥ 50 and < 70 years; and Group 3 - age ≥ 70 years. RESULTS: Of 284 patients identified, 278 were evaluable. The number of patients in each age group was: Group 1 - 51; Group 2 - 140; and Group 3 - 93. Baseline and treatment characteristics, tumor stage, rates of overall acute toxicity, need for unplanned treatment breaks and chemotherapy delivery were largely similar across the age groups. However, nine patients in Group 3 did not complete CRT, compared with five and none in Groups 1 and 2, respectively (p = 0.006). In addition, five patients in Group 3 had diarrhea requiring treatment break, compared with none in the other two groups (p = 0.004). At a median follow-up 5.3 years, there was no significant difference in overall survival (p = 0.11), disease-free survival (p = 0.22) or local-recurrence free survival (p = 0.34), across the three age groups. CONCLUSIONS: CRT is safe and tolerable in the elderly age group, and provides equivalent disease control rates compared with the younger age group. Age alone should therefore not preclude aggressive curative treatment.

Survival outcomes for women with a solitary extracranial metastasis from breast cancer.

BACKGROUND: Aggressive metastasis directed treatment of extracranial oligometastatic breast cancer with the aim of increasing disease-free survival has emerged as a new potential treatment paradigm, however there is currently a lack of data to assist in identifying the subset of patients who will potentially benefit most. This single-institute retrospective cohort study aimed to evaluate survival outcomes for patients with a solitary extracranial metastasis from breast cancer and to assess for significant prognostic factors. METHODS AND MATERIALS: Medical records of 70 female breast cancer patients with a solitary extracranial metastasis actively managed at the Peter MacCallum Cancer Centre (PMCC) Melbourne Campus between 2000 and 2019 were reviewed. Kaplan-Meier curves were used to estimate overall survival (OS), local progression free survival (LPFS) and distant progression free survival (DPFS). RESULTS: Median follow-up period was 9.4 years. The study included 40 hormone receptor positive/HER2 negative (HR+HER2-), 14 hormone receptor positive/HER2 positive (HR+HER2+), 3 hormone receptor negative/HER2 positive (HR-HER2+), 9 triple negative (TNBC) and 4 unclassified breast cancer patients. 5-year OS rate for all patients was 46%, LPFS rate was 56% and DPFS was 20%. Tumour receptor group had a statistically significant association with OS and DPFS rates. TNBC patients had significantly poorer OS and DPFS rates in comparison to HR+HER2-patients. CONCLUSION: Among patients with a solitary extracranial metastasis from breast cancer, TNBC was associated with the poorest OS and DPFS rates. Identification of other significant prognostic factors for oligometastatic breast cancer patients may inform guidelines for metastasis directed treatments.

Assessment of cervical spine CT by an image quality audit using qualitative and quantitative methods.

INTRODUCTION: To study the feasibility and assess the correlation of qualitative and quantitative methods for an image quality (IQ) audit of a Cervical spine CT. METHODS: Five radiologists retrospectively performed a blinded visual grading analysis (VGA) on 20 studies (10 from Protocol 1 and 10 from Protocol 2), using the RANZCR CT IQ Self-Audit worksheet. A Visual Grading Analysis Score (VGAS) and Area under the curve using Visual Grading Characteristics (AUCVGC) were the figures of merit. Quantitative metrics for noise and contrast were correlated to the qualitative assessment. RESULTS: No statistically significant difference was observed in the IQ, VGASProtocol 1 = 0.65, 95% CI [0.54, 0.75] and VGASProtocol 2 = 0.73, 95% CI [0.67, 0.79] and AUCVGC = 0.548, 95% CI [0.40, 0.69]. Protocol 2 indicated a statistically significant average dose reduction of 35% in CTDIvol (P = 0.020) and a higher noise; however, the difference was statistically insignificant. There was a moderate correlation between the manual noise measurements in soft tissue and air (P = 0.035) and a strong correlation between the manual and automated noise measurements (P < 0.001). The contrast resolution-based quantitative parameter, EdgeGradientSoft, correlated to the qualitative scores (P = 0.031). CONCLUSION: Validated VGA tools can be used for IQ audits; however, tailoring the image criteria and rating scale to the clinical practice is suggested. The use of contrast-based IQ metrics showed encouraging results, and further larger-scale studies are needed to explore their potential use in quality management.

Uncertainty estimation using a 3D probabilistic U-Net for segmentation with small radiotherapy clinical trial datasets.

BACKGROUND AND OBJECTIVES: Bio-medical image segmentation models typically attempt to predict one segmentation that resembles a ground-truth structure as closely as possible. However, as medical images are not perfect representations of anatomy, obtaining this ground truth is not possible. A surrogate commonly used is to have multiple expert observers define the same structure for a dataset. When multiple observers define the same structure on the same image there can be significant differences depending on the structure, image quality/modality and the region being defined. It is often desirable to estimate this type of aleatoric uncertainty in a segmentation model to help understand the region in which the true structure is likely to be positioned. Furthermore, obtaining these datasets is resource intensive so training such models using limited data may be required. With a small dataset size, differing patient anatomy is likely not well represented causing epistemic uncertainty which should also be estimated so it can be determined for which cases the model is effective or not. METHODS: We use a 3D probabilistic U-Net to train a model from which several segmentations can be sampled to estimate the range of uncertainty seen between multiple observers. To ensure that regions where observers disagree most are emphasised in model training, we expand the Generalised Evidence Lower Bound (ELBO) with a Constrained Optimisation (GECO) loss function with an additional contour loss term to give attention to this region. Ensemble and Monte-Carlo dropout (MCDO) uncertainty quantification methods are used during inference to estimate model confidence on an unseen case. We apply our methodology to two radiotherapy clinical trial datasets, a gastric cancer trial (TOPGEAR, TROG 08.08) and a post-prostatectomy prostate cancer trial (RAVES, TROG 08.03). Each dataset contains only 10 cases each for model development to segment the clinical target volume (CTV) which was defined by multiple observers on each case. An additional 50 cases are available as a hold-out dataset for each trial which had only one observer define the CTV structure on each case. Up to 50 samples were generated using the probabilistic model for each case in the hold-out dataset. To assess performance, each manually defined structure was matched to the closest matching sampled segmentation based on commonly used metrics. RESULTS: The TOPGEAR CTV model achieved a Dice Similarity Coefficient (DSC) and Surface DSC (sDSC) of 0.7 and 0.43 respectively with the RAVES model achieving 0.75 and 0.71 respectively. Segmentation quality across cases in the hold-out datasets was variable however both the ensemble and MCDO uncertainty estimation approaches were able to accurately estimate model confidence with a p-value < 0.001 for both TOPGEAR and RAVES when comparing the DSC using the Pearson correlation coefficient. CONCLUSIONS: We demonstrated that training auto-segmentation models which can estimate aleatoric and epistemic uncertainty using limited datasets is possible. Having the model estimate prediction confidence is important to understand for which unseen cases a model is likely to be useful.

Comparison of high spatial resolution respiratory triggered inversion recovery-prepared spoiled gradient echo sequence with standard breathhold T1 sequence MRI of the liver using gadoxetic acid.

PURPOSE: To assess if a high resolution respiratory triggered inversion recovery prepared GRE sequence (RT) improved image quality and detection of lesions compared with breathhold GRE T1 weighted MR sequence (BH) in the hepatobiliary uptake phase of MR of the liver using gadoxetic acid (Gd-EOB-DTPA). MATERIALS AND METHODS: Thirty-eight consecutive patients from July 2009 to September 2010 who had undergone Gd-EOB-DTPA enhanced liver exams were retrospectively identified. Qualitative assessment performed on reference lesions and background liver by two independent readers. Quantitative assessment performed by one reader. RESULTS: Liver parenchyma signal-to-noise ratio for BH was 90.3 ± 23.9 (mean ± SD) and RT, 106.1 ± 40.4 (P = 0.119). For BH, 320 lesions were detected compared with 257 for RT. Lesion to liver contrast was significantly better on RT sequences (0.26 ± 0.24; mean ± SD) compared with BH sequence (0.21 ± 0.20; P = 0.044). Fifty-seven reference lesions assessed. Both reviewers rated BH better for lesion margin and hepatic vessel sharpness. BH was rated with less artifact (P < 0.05). Lesion to liver contrast on BH was significantly better for one reviewer. CONCLUSION: BH sequence had better overall image quality than RT in several quantitative and qualitative factors including number of lesions detected and level of artifact.

Towards comprehensive evaluation of the FLEXotendon glove-III: a case series evaluation in pediatric clinical cases and able-bodied adults.

Injuries involving the nervous system, such as a brachial plexus palsy or traumatic brain injury, can lead to impairment in the functionality of the hand. Assistive robotics have been proposed as a possible method to improve patient outcomes in rehabilitation. The work presented here evaluates the FLEXotendon Glove-III, a 5 degree-of-freedom, voice-controlled, tendon-driven soft robotic hand exoskeleton, with two human subjects with hand impairments and four able-bodied subjects. The FLEXotendon Glove-III was evaluated on four unimpaired subjects, in conjunction with EMG sensor data, to determine the quantitative performance of the glove in applied pinch force, perturbation resistance, and exertion reduction. The exoskeleton system was also evaluated on two subjects with hand impairments, using two standardized hand function tests, the Jebsen-Taylor Hand Function Test and the Toronto Rehabilitation Institute Hand Function Test. The subjects were also presented with three qualitative questionnaires, the Capabilities of Upper Extremities Questionnaire, the Quebec User Evaluation of Satisfaction with Assistive Technology, and the Orthotics Prosthetics User Survey-Satisfaction module. From the previous design, minor design changes were made to the exoskeleton. The quick connect system was redesigned for improved performance, the number of motors was reduced to decrease overall footprint, and the entire system was placed into a compact acrylic case that can be placed into a backpack for increased portability.

Evaluation of the FLEXotendon glove-III through a human subject case study.

Cervical spinal cord injury (SCI) can significantly impair an individual's hand functionality due to the disruption of nerve signals from the brain to the upper extremity. Robotic assistive hand exoskeletons have been proposed as a potential technology to facilitate improved patient rehabilitation outcomes, but few exoskeleton studies utilize standardized hand function tests and questionnaires to produce quantitative data regarding exoskeleton performance. This work presents the human subject case study evaluation of the FLEXotendon Glove-III, a 5 degree-of-freedom voice-controlled, tendon-driven soft robotic assistive hand exoskeleton for individuals with SCI. The exoskeleton system was evaluated in a case study with two individuals with SCI through two standardized hand function tests namely, the Jebsen-Taylor Hand Function Test and the Toronto Rehabilitation Institute Hand Function Test and three questionnaires (Capabilities of Upper Extremities Questionnaire, Orthotics Prosthetics Users Survey, Quebec User Evaluation of Satisfaction with Assistive Technology). Minor design changes were made to the exoskeleton: integrated fingertip force sensors to sense excessive grasp force, a quick connect system to expedite the exoskeleton glove swapping process between users, compact tendon tension sensors to measure tendon force for admittance control, and a redesigned smartphone app to encompass all aspects of exoskeleton use.

Accuracy of after-hours trauma cervical spine CT reporting by radiology trainees: Experiences from two Australian teaching hospitals.

INTRODUCTION: Like many teaching hospitals in Australia, after-hours computed tomography (CT) reporting at our institution is undertaken by the on-call radiology registrar. The accuracy of these reports is important as management is often initiated based on the interim findings, prior to review by the consultant radiologist. A common exception to this approach is cervical CT (CCT), as many hospital protocols recommend patients to remain in spinal precautions until the report is finalised by a consultant, although there are very few studies to support this practice. METHODS: The interim registrar reports for all CCTs performed after-hours over a 12-month period were retrospectively reviewed. The final consultant report was used as the gold standard to establish accuracy of the registrar report. The primary outcome was discrepancy between the provisional and final reports. Any discrepancy was classified as either an 'overcall' or 'miss'. Discrepancies were graded by the RADPEER scoring system. RESULTS: A total of 1084 after-hours CCT studies were reviewed. The number of cases positive for injury was 37 (3.4%). The total number of discrepancies was 14 (discrepancy rate 1.3%), including 4 overcalls (0.3%) and 10 misses (0.9%). The discrepancy rates for junior and senior registrars were 1.7% and 0.7% respectively. Only 5 misses (0.5%) were considered clinically significant. CONCLUSION: Registrars reporting after-hours CCT have low rates of discrepancy with very few clinically significant misses. However, the reduced registrar sensitivity for detection of cervical injury highlights the ongoing importance of consultant review in the process of cervical spine clearance pathways.

Electric hearing and tinnitus suppression by noninvasive ear stimulation.

While noninvasive brain stimulation is convenient and cost effective, its utility is limited by the substantial distance between scalp electrodes and their intended neural targets in the head. The tympanic membrane, or eardrum, is a thin flap of skin deep in an orifice of the head that may serve as a port for improved efficiency of noninvasive stimulation. Here we chose the cochlea as a target because it resides in the densest bone of the skull and is adjacent to many deep-brain-stimulation structures. We also tested the hypothesis that noninvasive electric stimulation of the cochlea may restore neural activities that are missing in acoustic stimulation. We placed an electrode in the ear canal or on the tympanic membrane in 25 human adults (10 females) and compared their stimulation efficiency by characterizing the electrically-evoked auditory sensation. Relative to ear canal stimulation, tympanic membrane stimulation was four times more likely to produce an auditory percept, required eight times lower electric current to reach the threshold and produced two-to-four times more linear suprathreshold responses. We further measured tinnitus suppression in 14 of the 25 subjects who had chronic tinnitus. Compared with ear canal stimulation, tympanic membrane stimulation doubled both the probability (22% vs. 55%) and the amount (-15% vs. -34%) of tinnitus suppression. These findings extended previous work comparing evoked perception and tinnitus suppression between electrodes placed in the ear canal and on the scalp. Together, the previous and present results suggest that the efficiency of conventional scalp-based noninvasive electric stimulation can be improved by at least one order of magnitude via tympanic membrane stimulation. This increased efficiency is most likely due to the shortened distance between the electrode placed on the tympanic membrane and the targeted cochlea. The present findings have implications for the management of tinnitus by offering a potential alternative to interventions using invasive electrical stimulation such as cochlear implantation, or other non-invasive transcranial electrical stimulation methods.

Cardiac papillary fibroelastoma as a cause of acute coronary syndrome.

Cardiac papillary fibroelastoma (CPF) is a benign primary cardiac neoplasm, commonly found in men and above 40 years old. The clinical presentation of CPF ranges from asymptomatic to embolism-related complications such as stroke, myocardial ischemia, infarction, or ventricular fibrillation. Acute coronary syndrome is a rare complication of CPF, which was reported only in a few cases in medical literature. Hence, we report a case of a 50-year-old female with a CPF on the right coronary cusp of the aortic valve diagnosed with multi-modality imaging with definitive diagnosis through histopathologic confirmation. The patient presented with acute onset of fatigue, diaphoresis, and vomiting. Initial electrocardiogram (ECG) demonstrated T wave inversion in aVL. Repeated ECG two hours later showed persistent T wave inversion in aVL with new T wave inversions in lead I and ST depression in V2-V6. Troponin levels were elevated from 3.6 ng/L to 1503 ng/L but the patient did not report chest pain, abdominal pain, or dyspnea. Computed tomography coronary angiography did not show any significant coronary stenosis but revealed a low attenuation node with 7 × 6 mm in dimension attached to the right coronary cusp of the aortic valve. Treatment was discussed among a multidisciplinary team and the CPF was surgically removed. Learning objective: Acute coronary syndrome is a rare, but potentially fatal complication of cardiac papillary fibroelastoma (CPF). Multi-modality imaging is valuable in delineating the evaluation of exact position, dimensions, nature of cardiac masses, diagnostic workup, and preliminary assessment before the surgery. There are no clear guidelines for the treatment of CPF.

A case report of coronary pulmonary artery fistula detected by transthoracic echocardiography in an elderly patient with dyspnea.

Coronary pulmonary artery fistula (CPAF) is a rare entity in the population. It may present with multiple clinical settings and in various age ranges. Invasive coronary angiography (ICA), coronary computed tomography angiography (CCTA), and transthoracic echocardiography (TTE) have been reported as diagnostic tools for CPAF. Among them, TTE is rarely capable of identifying CPAF. There is no current treatment guideline as some of the interventional therapies are effective yet controversial. The therapy therefore should be individualized. We report a case of CPAF accidentally detected by TTE in a 93-year-old female who presented with acute respiratory distress on the setting of community-acquired pneumonia, diastolic heart failure, ischemic heart disease, pulmonary hypertension, chronic kidney disease, and hypertension. The patient presented with orthopnea, fever, bilateral pleuritic chest pain, and productive cough with yellowish sputum for 7 days. She had no previous chest trauma or surgical intervention. TTE demonstrated the tortuous enlargement of left coronary artery which drains into the pulmonary arterial trunk right above the pulmonary valve. As the patient was in advanced age with multiple comorbidities; we offered a conservative management including diuretic, oxygen therapy, antibiotic, antiplatelet, and statin. She recovered following a 13-day hospitalization. To our knowledge, this is the oldest case report of suspected congenital CPAF which is particularly detected by TTE.

Outcomes of curative (chemo)radiotherapy for patients with non-p16 positive head and neck squamous cell carcinoma who are borderline for curative treatment.

INTRODUCTION: Appropriate selection of head and neck squamous cell cancer (HNSCC) patients for curative treatment is difficult, and it is a very understudied issue. The aim of this study was to review the outcomes of curative intent treatment in non-p16 positive HNSCC patients assessed as having borderline curability. METHODS: A single institution retrospective review of the clinical outcomes of non-p16 positive HNSCC patients with borderline curability. Predefined criteria for borderline curability were as follows: (i) T4 and/or N3 disease; or (ii) ECOG status ≥2; or (iii) age ≥75 years. RESULTS: A total of 114 patients were identified. A total of 56 had N3/T4, 32 were >ECOG 2 and 57 were >75 years. A total of 29 had two or more borderline curability criteria. Progression-free survival rate (PFS) at 1 and 2 years was 72% (95% confidence interval (CI), 63-79) and 53% (95% CI, 43-62), respectively. Overall survival (OS) at 1 and 2 years was 76% (95% CI, 67-83) and 61% (95% CI, 51-69), respectively. On multivariable analysis, the only independent prognostic factor for OS was the adult comorbidity evaluation-27 (ACE-27) grade (HR 1.4; 95% CI, 1.1-1.8; P = 0.018). CONCLUSIONS: Patients with borderline curability criteria treated with curative intent achieved good PFS and OS. ACE-27 was an important prognostic factor in this population.

Adverse respiratory outcomes following conventional long-course radiotherapy for non-small-cell lung cancer in patients with pre-existing pulmonary fibrosis: A comparative retrospective study.

INTRODUCTION: There is some evidence to suggest that patients with underlying pulmonary fibrosis (PF) have increased risk of adverse respiratory and survival outcomes, when treated with conventional, long-course radiotherapy (RT) for non-small-cell lung cancer (NSCLC). We performed a retrospective analysis to determine the size of these risks. METHODS: Data from 21 patients with PF (cases) were retrospectively analysed for respiratory toxicity and mortality outcomes, and compared with 84 patients without PF (non-cases). Age and mean lung dose were included as covariates in regression analyses. The additional predictive value of other patient, disease and treatment characteristics on radiation pneumonitis (RP) risk and severity was explored. RESULTS: There was a numerical (though not statistically significant) increase in grade ≥ 2 RP among PF cases (OR 2.74, P = 0.074). Cases were significantly more likely to discontinue radical treatment early (OR 6.10, P = 0.015). There was a significant association between increased RP severity and underlying PF (P = 0.039), with RP strongly implicated in the death in 3 of 21 cases (14.3%) compared to 1 non-case (1.2%). Cases experienced increased grade ≥ 2 respiratory toxicity otherwise (OR 4.35, P = 0.020) and poorer median overall survival (0.6 versus 1.7 years, P < 0.001). Two cases, and no non-cases, died during the proposed RT period. None of the analysed patient, disease or treatment factors, was a significant additional predictor of RP risk/severity. CONCLUSION: Patients with PF are at increased risk of treatment discontinuation, respiratory morbidity and mortality, and poor survival following conventional RT for NSCLC. Caution should be exercised when offering high-dose RT to these patients.

Tinnitus Treatment Using Noninvasive and Minimally Invasive Electric Stimulation: Experimental Design and Feasibility.

Noninvasive transcranial or minimally invasive transtympanic electric stimulation may offer a desirable treatment option for tinnitus because it can activate the deafferented auditory nerve fibers while posing little to no risk to hearing. Here, we built a flexible research interface to generate and control accurately charge-balanced current stimulation as well as a head-mounted instrument capable of holding a transtympanic electrode steady for hours. We then investigated the short-term effect of a limited set of electric stimulation parameters on tinnitus in 10 adults with chronic tinnitus. The preliminary results showed that 63% of conditions of electric stimulation produced some degree of tinnitus reduction, with total disappearance of tinnitus in six subjects in response to at least one condition. The present study also found significant side effects such as visual, tactile, and even pain sensations during electric stimulation. In addition to masking and residual inhibition, neuroplasticity is likely involved in the observed tinnitus reduction. To translate the present electric stimulation into a safe and effective tinnitus treatment option, we need to optimize stimulation parameters that activate the deafferented auditory nerve fibers and reliably suppress tinnitus, with minimal side effects and tolerable sensations. Noninvasive or minimally invasive electric stimulation can be integrated with sound therapy, invasive cochlear implants, or other forms of coordinated stimulation to provide a systematic strategy for tinnitus treatment or even a cure.

Human Sensation of Transcranial Electric Stimulation.

Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug side-effects. However, not only is there limited evidence for activation of deep tissues by transcranial electric stimulation, its evoked human sensation is understudied and often dismissed as a placebo or secondary effect. By systematically characterizing the human sensation evoked by transcranial alternating-current stimulation, we observed not only stimulus frequency and electrode position dependencies specific for auditory and visual sensation but also a broader presence of somatic sensation ranging from touch and vibration to pain and pressure. We found generally monotonic input-output functions at suprathreshold levels, and often multiple types of sensation occurring simultaneously in response to the same electric stimulation. We further used a recording circuit embedded in a cochlear implant to directly and objectively measure the amount of transcranial electric stimulation reaching the auditory nerve, a deep intercranial target located in the densest bone of the skull. We found an optimal configuration using an ear canal electrode and low-frequency (<300 Hz) sinusoids that delivered maximally ~1% of the transcranial current to the auditory nerve, which was sufficient to produce sound sensation even in deafened ears. Our results suggest that frequency resonance due to neuronal intrinsic electric properties need to be explored for targeted deep brain stimulation and novel brain-computer interfaces.

Saphenous vein graft aneurysm and fistula with compression mimicking mitral stenosis.

We present the case of a patient who presented with acute coronary syndrome and was found to have a mass compressing the left atrium. An angiogram revealed a large saphenous vein graft aneurysm with a fistula into a cardiac chamber, presumed to be the left ventricle. The patient also developed a functional mitral stenosis secondary to this mass causing left atrial compression. The patient passed away prior to receiving surgery. We describe a rare case of venous graft aneurysm with compression and fistula to a chamber other than the right atrium, that to our knowledge has yet to be reported.