Updates in global oncology: Advancements and future directions.

Globally, cancer is the second leading cause of death, and low- and middle-income countries bear most of the disease burden. While cancer is increasingly recognized as a major global health issue, more work remains. Understanding the status of global cancer care will shape the next steps in ensuring equitable global access to cancer care. This article highlights ongoing initiatives in global oncology and the next steps in advancing the field.

Stereo-electroencephalographic seizure localization in patients with mesial temporal sclerosis: A single center experience.

Objective: Epilepsy patients with mesial temporal sclerosis (MTS) on imaging who are drug-resistant usually undergo epilepsy surgery without previous invasive evaluation. However, up to one-third of patients are not seizure-free after surgery. Prior studies have identified risk factors for surgical failure, but it is unclear if they are associated with bilateral or discordant seizure onset. Methods: In this retrospective case series, we identified 17 epilepsy patients who had MRI-confirmed MTS but received invasive stereo-EEG (SEEG) evaluation before definitive intervention. We analyzed their presurgical risk factors in relation to SEEG seizure onset localization and MRI/SEEG concordance. Results: SEEG ictal onset was concordant with MTS localization (i.e. seizures started only from the hippocampus with MTS) in 5 out of 13 patients with unilateral MTS (UMTS) and in 3 out of 4 patients with bilateral MTS.No statistically significant association regarding concordance of SEEG ictal onset and MTS location was found in patients with such risk factors as a history of non-mesial temporal aura, frequent focal to bilateral tonic-clonic seizures, prior viral brain infection, or family history of epilepsy. Nine out of 13 UMTS patients had resective surgery only, 5 out of 9 (56 %) have Engel class I outcome at most recent follow-up (median 46.5 months, range 22-91 months). In Engel class I cohort, the SEEG ictal onset was concordant with MTS location in 3 out of 5 patients, and 2 patients had ipsilateral temporal neocortical ictal onset. Conclusions: Our findings suggest that patients with MTS might have discordant SEEG ictal onset (in 61.5% patients with UMTS in presented cohort), which may explain poor surgical outcome after destructive surgery in these cases. Significance: Although no statistically significant association was found in this under-powered study, these findings could be potentially valuable for future meta-analyses.

Real-Time Seizure Detection Using Behind-the-Ear Wearable System.

INTRODUCTION: This study examines the usability and comfort of a behind-the-ear seizure detection device called brain seizure detection (BrainSD) that captures ictal electroencephalogram (EEG) data using four scalp electrodes. METHODS: This is a feasibility study. Thirty-two patients admitted to a level 4 Epilepsy Monitoring Unit were enrolled. The subjects wore BrainSD and the standard 21-channel video-EEG simultaneously. Epileptologists analyzed the EEG signals collected by BrainSD and validated it using video-EEG data to confirm its accuracy. A poststudy survey was completed by each participant to evaluate the comfort and usability of the device. In addition, a focus group of UT Southwestern epileptologists was held to discuss the features they would like to see in a home EEG-based seizure detection device such as BrainSD. RESULTS: In total, BrainSD captured 11 of the 14 seizures that occurred while the device was being worn. All 11 seizures captured on BrainSD had focal onset, with three becoming bilateral tonic-clonic and one seizure being of subclinical status. The device was worn for an average of 41 hours. The poststudy survey showed that most users found the device comfortable, easy-to-use, and stated they would be interested in using BrainSD. Epileptologists in the focus group expressed a similar interest in BrainSD. CONCLUSIONS: Brain seizure detection is able to detect EEG signals using four behind-the-ear electrodes. Its comfort, ease-of-use, and ability to detect numerous types of seizures make BrainSD an acceptable at-home EEG detection device from both the patient and provider perspective.

Classification of electrically-evoked potentials in the parkinsonian subthalamic nucleus region.

Electrically evoked compound action potentials (ECAPs) generated in the subthalamic nucleus (STN) contain features that may be useful for titrating deep brain stimulation (DBS) therapy for Parkinson's disease. Delivering a strong therapeutic effect with DBS therapies, however, relies on selectively targeting neural pathways to avoid inducing side effects. In this study, we investigated the spatiotemporal features of ECAPs in and around the STN across parameter sweeps of stimulation current amplitude, pulse width, and electrode configuration, and used a linear classifier of ECAP responses to predict electrode location. Four non-human primates were implanted unilaterally with either a directional (n = 3) or non-directional (n = 1) DBS lead targeting the sensorimotor STN. ECAP responses were characterized by primary features (within 1.6 ms after a stimulus pulse) and secondary features (between 1.6 and 7.4 ms after a stimulus pulse). Using these features, a linear classifier was able to accurately differentiate electrodes within the STN versus dorsal to the STN in all four subjects. ECAP responses varied systematically with recording and stimulating electrode locations, which provides a subject-specific neuroanatomical basis for selecting electrode configurations in the treatment of Parkinson's disease with DBS therapy.

Spatiotemporal scaling changes in gait in a progressive model of Parkinson's disease.

Objective: Gait dysfunction is one of the most difficult motor signs to treat in patients with Parkinson's disease (PD). Understanding its pathophysiology and developing more effective therapies for parkinsonian gait dysfunction will require preclinical studies that can quantitatively and objectively assess the spatial and temporal features of gait. Design: We developed a novel system for measuring volitional, naturalistic gait patterns in non-human primates, and then applied the approach to characterize the progression of parkinsonian gait dysfunction across a sequence of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatments that allowed for intrasubject comparisons across mild, moderate, and severe stages. Results: Parkinsonian gait dysfunction was characterized across treatment levels by a slower stride speed, increased time in both the stance and swing phase of the stride cycle, and decreased cadence that progressively worsened with overall parkinsonian severity. In contrast, decreased stride length occurred most notably in the moderate to severe parkinsonian state. Conclusion: The results suggest that mild parkinsonism in the primate model of PD starts with temporal gait deficits, whereas spatial gait deficits manifest after reaching a more severe parkinsonian state overall. This study provides important context for preclinical studies in non-human primates studying the neurophysiology of and treatments for parkinsonian gait.

Post-operative haemorrhage secondary to cinnamon use. A case report.

INTRODUCTION: Herbal medicine plays a significant role in modern medicine. The difficulty in integrating the two, lies in the unknown quantities of active ingredients in herbal remedies. This proved true in this clinical scenario. The quantity of coumarin, in the form of cinnamon ingested by this patient over ten months is unknown. The only quantifiable measure was the derangement in his extrinsic coagulation pathway. PRESENTATION OF CASE: A 49-year-old male with a history of celiac disease presented with haematochezia secondary to a malignant adenocarcinoma of the transverse colon. The patient underwent a laparoscopic subtotal colectomy and on the second post-operative day, he was noted to have peritonitis and a positive Fox sign. Diagnostic laparoscopy confirmed intraabdominal bleeding. Over the next four days, the patient's haemoglobin plummeted from 17.4 g/dL to 8.0 g/dL. Investigations revealed an INR of 1.59, which led to further questioning into dietary practices. The patient admitted he had been taking Ceylon cinnamon one tablespoon daily for ten months in the period leading up to surgery. DISCUSSION: Coumarin is a chemical compound readily available in food items such as cinnamon. Coumarin possesses the ability to inhibit vitamin K epoxide reductase complex 1 which is responsible for the recycling of vitamin K. This impedes the gamma-carboxylation of coagulation factors II, VII, IX, X. Vitamin K antagonism can manifest as a prolonged INR and normal activated partial thromboplastin time. CONCLUSION: Bleeding diathesis secondary to dietary coumarin is a rare but dangerous phenomenon that emphasizes the need for a thorough interrogation into a patient's dietary history.

The utility of the Altemeier procedure in strangulated rectal procidentia secondary to rectal cancer. A case report.

INTRODUCTION AND IMPORTANCE: Altemeier rectosigmoidectomy has been cited in the literature as a suitable approach for incarcerated rectal prolapse when a large segment of bowel is involved. However, the literature is devoid of cases that employed the technique as an oncological procedure for rectal carcinoma. For this reason, this case report heralds a new perspective on an old technique. CASE PRESENTATION: We describe the case of a male in his 6th decade who presented with stage four rectal cancer. Computed tomography imaging showed a rectal mass at the rectosigmoid junction with pelvic lymphadenopathy and a solitary hepatic lesion in segment two of the liver. While admitted to the hospital a 16 cm segment of bowel containing the mass prolapsed and became incarcerated, eventually becoming necrotic. A modification of the Altemeier procedure was performed along with a diverting ileostomy and hepatic wedge resection of the solitary metastases. Histological assessment of the surgical specimens confirmed that adequate resection margins were obtained with one of twenty-one lymph nodes positive for malignancy. He is currently being followed up in the outpatient oncology clinic and has commenced adjuvant chemotherapy. CLINICAL DISCUSSION: Synchronous excision of rectal carcinoma with hepatic metastasectomy is a feasible surgery even in the emergency setting and can offer improved patient survival. CONCLUSION: The combination of both an abdominal and perineal approach was suitable for this patient given his improved quality of life and negative pathological margins.

Longitudinal analysis of local field potentials recorded from directional deep brain stimulation lead implants in the subthalamic nucleus.

Objective.The electrode-tissue interface surrounding a deep brain stimulation (DBS) lead is known to be highly dynamic following implantation, which may have implications on the interpretation of intraoperatively recorded local field potentials (LFPs). We characterized beta-band LFP dynamics following implantation of a directional DBS lead in the sensorimotor subthalamic nucleus (STN), which is a primary target for treating Parkinson's disease.Approach.Directional STN-DBS leads were implanted in four healthy, non-human primates. LFPs were recorded over two weeks and again 1-4 months after implantation. Impedance was measured for two weeks post-implant without stimulation to compare the reactive tissue response to changes in LFP oscillations. Beta-band (12-30 Hz) peak power was calculated from the LFP power spectra using both common average referencing (CAR) and intra-row bipolar referencing (IRBR).Results.Resting-state LFPs in two of four subjects revealed a steady increase of beta power over the initial two weeks post-implant whereas the other two subjects showed variable changes over time. Beta power variance across days was significantly larger in the first two weeks compared to 1-4 months post-implant in all three long-term subjects. Further, spatial maps of beta power several hours after implantation did not correlate with those measured two weeks or 1-4 months post-implant. CAR and IRBR beta power correlated across short- and long-term time points. However, depending on the time period, subjects showed a significant bias towards larger beta power using one referencing scheme over the other. Lastly, electrode-tissue impedance increased over the two weeks post-implant but showed no significant correlation to beta power.Significance.These results suggest that beta power in the STN may undergo significant changes following DBS lead implantation. DBS lead diameter and electrode recording configurations can affect the post-implant interpretation of oscillatory features. Such insights will be important for extrapolating results from intraoperative and externalized LFP recordings.

Dose-dependent effects of transcranial alternating current stimulation on spike timing in awake nonhuman primates.

Weak extracellular electric fields can influence spike timing in neural networks. Approaches to noninvasively impose these fields on the brain have high therapeutic potential in neurology and psychiatry. Transcranial alternating current stimulation (TACS) is hypothesized to affect spike timing and cause neural entrainment. However, the conditions under which these effects occur in vivo are unknown. Here, we recorded single-unit activity in the neocortex in awake nonhuman primates during TACS and found dose-dependent neural entrainment to the stimulation waveform. Cluster analysis of changes in interspike intervals identified two main types of neural responses to TACS-increased burstiness and phase entrainment. Our results uncover key mechanisms of TACS and show that the stimulation affects spike timing in the awake primate brain at intensities feasible in humans. Thus, novel TACS protocols tailored to ongoing brain activity may be a tool to normalize spike timing in maladaptive brain networks and neurological disease.

Distributed acoustic cues for caller identity in macaque vocalization.

Individual primates can be identified by the sound of their voice. Macaques have demonstrated an ability to discern conspecific identity from a harmonically structured 'coo' call. Voice recognition presumably requires the integrated perception of multiple acoustic features. However, it is unclear how this is achieved, given considerable variability across utterances. Specifically, the extent to which information about caller identity is distributed across multiple features remains elusive. We examined these issues by recording and analysing a large sample of calls from eight macaques. Single acoustic features, including fundamental frequency, duration and Weiner entropy, were informative but unreliable for the statistical classification of caller identity. A combination of multiple features, however, allowed for highly accurate caller identification. A regularized classifier that learned to identify callers from the modulation power spectrum of calls found that specific regions of spectral-temporal modulation were informative for caller identification. These ranges are related to acoustic features such as the call's fundamental frequency and FM sweep direction. We further found that the low-frequency spectrotemporal modulation component contained an indexical cue of the caller body size. Thus, cues for caller identity are distributed across identifiable spectrotemporal components corresponding to laryngeal and supralaryngeal components of vocalizations, and the integration of those cues can enable highly reliable caller identification. Our results demonstrate a clear acoustic basis by which individual macaque vocalizations can be recognized.

Absence of the appendix discovered during childhood.

Absence of the appendix is rare. Isolated cases are usually discovered in adult patients or cadavers. We report the case of a 14 year old boy who was found to have no appendix on laparotomy for assumed acute appendicitis and use this opportunity to highlight the growing surgical uses of this vestigial structure.

The incidence of ventilator-associated pneumonia using the PneuX System with or without elective endotracheal tube exchange: A pilot study.

BACKGROUND: The PneuX System is a novel endotracheal tube and tracheal seal monitor, which has been designed to minimise the aspiration of oropharyngeal secretions. We aimed to determine the incidence of ventilator-associated pneumonia (VAP) in patients who were intubated with the PneuX System and to establish whether intermittent subglottic secretion drainage could be performed reliably and safely using the PneuX System. FINDINGS: In this retrospective observational study, data was collected from 53 sequential patients. Nine (17%) patients were initially intubated with the PneuX System and 44 (83%) patients underwent elective exchange to the PneuX System. There were no episodes of VAP while the PneuX System was in situ. On an intention to treat basis, the incidence VAP was 1.8%. There were no complications from, or failure of, subglottic secretion drainage during the study. CONCLUSIONS: Our study demonstrates that a low incidence of VAP is possible using the PneuX System. Our study also demonstrates that elective exchange and intermittent subglottic secretion drainage can be performed reliably and safely using the PneuX System.

A change in humidification system can eliminate endotracheal tube occlusion.

PURPOSE: Inadequate airway humidification can result in endotracheal tube occlusion. There is evidence that heat and moisture exchangers (HMEs) are more prone to endotracheal tube occlusion than heated humidifiers (HHs) that contain a heated wire circuit. We aimed to compare the incidence of endotracheal tube occlusion while introducing a new dual-heated wire circuit HH in place of an established hydrophobic HME. MATERIALS AND METHODS: This was a prospective observational study. All patients who required intubation were included in our analysis. Univariate statistical analysis was performed using a Fisher exact test. P < .05 was considered statistically significant. RESULTS: There were 158 patients in the HME group and 88 patients in the HH group. The incidence of endotracheal tube occlusion was 5.7% in the HME group and 0% in the HH group. Statistical analysis revealed a significant difference between the 2 groups (P = .02). In light of this finding, we changed our practice to provide humidification exclusively by HH. In the subsequent 18-month period, there were no further episodes of endotracheal tube occlusion. CONCLUSIONS: Our study demonstrates that there is a significant increase in the incidence of endotracheal tube occlusion when using a hydrophobic HME compared with an HH and that using a dual-heated wire circuit HH can eliminate endotracheal tube occlusion.

The pressure exerted on the tracheal wall by two endotracheal tube cuffs: A prospective observational bench-top, clinical and radiological study.

BACKGROUND: The Lotrach endotracheal tube has a unique low-volume, low-pressure (LVLP) cuff, which has been designed to prevent pressure injury to the tracheal wall. We aimed to estimate the pressure exerted on the tracheal wall by the LVLP cuff and a conventional cuff in a bench-top, clinical and radiological study. METHOD: In the bench-top study, a model trachea was intubated with the LVLP cuff and the conventional cuff. The cuff pressure was controlled using a constant pressure device. We assessed the pressure exerted on the tracheal wall by measuring the ability of the cuffs to support a column of water using a standard protocol. In the clinical study, we tested the ability of both cuffs to prevent air leak during a staged recruitment manoeuvre. In the radiological study, we recorded the degree of anatomical distortion of the trachea from both cuffs in the antero-posterior (AP) and transverse tracheal diameters. We performed statistical analysis using non-inferiority tests. RESULTS: In the bench-top study, the LVLP cuff achieved a plateau at a mean height of 25.2 cmH2O (SD 0.34). In contrast, the conventional cuff failed to maintain any water above the cuff and a plateau could not be measured. In the clinical study, the mean pressure at which air leak occurred was 30.0 +/- 0.8 cmH2O (SD 3.8) using the LVLP cuff and 32.4 +/- 0.7 cmH2O (SD 3.0) using the conventional cuff. In the radiological study, the mean degree of anatomical distortion of the trachea in AP and transverse tracheal diameter was 2.9 +/- 2.2 mm (SD 2.1) and 1.8 +/- 1.4 mm (SD 1.4) using the LVLP cuff and 4.4 +/- 1.3 mm (SD 1.4) and 2.6 +/- 1.5 mm (SD 1.6) using the conventional cuff. CONCLUSIONS: The bench-top and clinical studies both demonstrated that the LVLP cuff exerted approximately 30 cmH2O of pressure on the tracheal wall. These results are supported by our radiological study. We conclude that the LVLP cuff exerts an acceptable amount of pressure on the tracheal wall when it is operated at the recommended intracuff pressure.

Extubation in intensive care units in the UK: an online survey.

AIM: To determine the current practice among critical care nurses in the UK with regard to airway management during cuff deflation and extubation. BACKGROUND: There are a number of techniques used by clinicians to prevent aspiration during cuff deflation and extubation of patients. There are no published clinical studies comparing the different manoeuvres available to clinicians at the time of extubation nor any data to suggest which technique is most commonly used. METHODS: All members of the British Association of Critical Care Nurses with an email address were invited to participate in an online survey. RESULTS: A total of 533 (29%) nurses from 184 (84%) intensive care unit (ICUs) in the UK completed the survey. Just under half of the sample (n = 258, 48.4%) had more than 10 years of critical care experience and the vast majority (n = 427, 80.1%) worked in general ICUs. The majority of respondents (n = 461, 86.5%) suction the trachea during cuff deflation and extubation. A further 304 (57%) respondents ask patients to cough as part of extubation. Respondents increase the positive end expiratory pressure setting on the ventilator infrequently as part of routine procedure for extubation (n = 7, 1.3%). CONCLUSION: The majority of UK critical care nurses either suction the trachea during cuff deflation and extubation of patients and/or simply ask the patient to cough. Further clinical trials are required to identify the most appropriate and safe technique for critically ill patients.

Increasing positive end expiratory pressure at extubation reduces subglottic secretion aspiration in a bench-top model.

AIM: To estimate the ability of simulated tracheal suction, adjusting the positive end expiratory pressure (PEEP) settings on the ventilator or compressing a self-inflating bag to minimize aspiration during cuff deflation and extubation in a bench-top model. BACKGROUND: During intubation, colonized secretions accumulate in the subglottic space above the endotracheal tube (ETT) cuff. Consequently, during cuff deflation and extubation, there is a risk of aspiration of the secretions. This may result in pneumonitis or pneumonia. There are a number of techniques used during cuff deflation and extubation to prevent secretion aspiration. METHOD: A model trachea was intubated and the proximal end of the ETT was attached to a mechanical ventilator. Ten millilitres of water was placed above the inflated cuff and then nine test protocols were implemented in a random order to simulate tracheal suction, adjusting the PEEP settings on the ventilator or compressing a self-inflating bag. The volume of water 'aspirated' by the model was determined by weighing the apparatus pre- and post-extubation. Statistical analysis was performed using regression analysis and heteroscedastic t tests with a Bonferroni correction. RESULTS: The level of PEEP was negatively correlated with the volume of fluid aspirated [co-efficient -0.24 (99% confidence interval -0.31 to -0.17), R(2) = 0.75]. Significantly less fluid was aspirated when a PEEP of 35 cmH(2)O was applied when compared with competing techniques. DISCUSSION AND CONCLUSIONS: This study suggests that applying PEEP during cuff deflation and extubation is protective against aspiration. We conclude that unless there is a contraindication, the application of PEEP should be considered when extubating patients.

Fission yeast Myo51 is a meiotic spindle pole body component with discrete roles during cell fusion and spore formation.

Class V myosins are dimeric actin-associated motor proteins that deliver cellular cargoes to discrete cellular locations. Fission yeast possess two class V myosins, Myo51 and Myo52. Although Myo52 has been shown to have roles in vacuole distribution, cytokinesis and cell growth, Myo51 has no as yet discernible function in the vegetative life cycle. Here, we uncover distinct functions for this motor protein during mating and meiosis. Not only does Myo51 transiently localise to a foci at the site of cell fusion upon conjugation, but overexpression of the Myo51 globular tail also leads to disruption of cell fusion. Upon completion of meiotic prophase Myo51 localises to the outside of the spindle pole bodies (SPBs), where it remains until completion of meiosis II. Association of Myo51 with SPBs is not dependent upon actin or the septation initiation network (SIN); however, it is dependent on a stable microtubule cytoskeleton and the presence of the Cdc2-CyclinB complex. We observe a rapid and dynamic exchange of Myo51 at the SPB during meiosis I but not meiosis II. Finally, we show that Myo51 has an important role in regulating spore formation upon completion of meiosis.

An insight into undiagnosed impaired glucose regulation.

Type 2 diabetes is responsible for considerable morbidity, mortality and cost to society. There is good evidence that lifestyle modification and pharmacological intervention are effective means of delaying, and possibly preventing, the onset of type 2 diabetes in individuals with impaired glucose regulation. The aim of this study was to estimate the number of patients treated at our district general hospital over a 28-day period who had impaired glucose regulation and so would be suitable candidates for intervention. The results reveal that 518 patients passed through our hospital during this period with evidence of impaired glucose regulation, but only 95 of these patients were formally investigated for diabetes. Of those who were investigated further, over one fifth were shown to have impaired glucose regulation. We suggest that a random plasma glucose test may provide a useful means to identify a population for formal screening for diabetes.