Concurrent management of suppurative intracranial complications of sinusitis and acute otitis media in children.

OBJECTIVE: Intracranial complications of sinusitis and acute otitis media (AOM) are rare but life-threatening events. In children with suppurative intracranial complications, concurrent neurosurgical and otolaryngological (ORL) intervention has been recommended to optimize outcomes. The aim of this study was to investigate outcomes following concurrent neurosurgical and ORL intervention. METHODS: A retrospective cohort study of children undergoing neurosurgical intervention for intracranial complications of sinusitis or AOM in two neurosurgical centres in Ireland was conducted. RESULTS: 65 children were identified. Mean age was 11.9 years. The most prevalent symptoms were headache, pyrexia, altered level of consciousness, facial swelling, and vomiting. Subdural empyema (n = 24, 36.9%) and extradural abscess (n = 17, 26.2%) were the most common complications. 54 underwent same admission ORL intervention; 47 (87%) were performed concurrently or earlier. For rhinogenic infections, 35 (64.8%) underwent endoscopic sinus surgery (ESS), 13 (24.1%) underwent frontal sinus trephine, and 5 (9.3%) underwent maxillary sinus washout alone. For otogenic infections, 10 (90.9%) underwent mastoidectomy and 7 (63.6%) underwent tympanostomy tube placement. 19 (29.2%) had post-operative neurological deficits, of which 2 (3.1%) were permanent. Streptococcus intermedius was the most common pathogen (n = 30, 46.2%). Concurrent intervention reduced the prevalence of residual collection (p = 0.018) and the need for revision neurosurgical intervention (p = 0.039) for sinogenic complications. The same trends did not achieve statistical significance for the otogenic group. Mortality was 0%. CONCLUSION: Intracranial complications of sinusitis and AOM are best managed in a specialist centre with multidisciplinary input. Concurrent ORL and neurosurgical intervention reduces abscess recurrence and requirement for revision neurosurgery in sinogenic complications and should represent the standard of care. ESS is the ORL modality of choice in experienced hands.

Epistaxis in the Sars-CoV-2 Era.

Introduction Epistaxis was the third most common unscheduled ENT surgical intervention in Ireland in 2019. Otorhinolaryngologists are exposed to a high viral reservoir of Sars-CoV-2, as they are dealing with pathology in the upper respiratory tract. Risk analysis is required to minimise nosocomial transmission. Methods A prospective audit of epistaxis management in the outpatients at a tertiary hospital was undertaken pre pandemic. A retrospective review of patients records during the Sars-CoV-2 pandemic. Comparative analysis was utilised to assess outcomes. Results Pre Sars-CoV-2 analysis revealed 14 patients (70%) were manged with rigid endoscopy compared to one (5%) interpandemic. Cauterization treated 20 patients (100%) pre pandemic and four patients (20%) interpandemic. Nasal packing modality differed in that 13 patients (65%) were treated with Nasopore pre pandemic and 14 (70%) with Rapid Rhino interpandemic. This exhibited a paradigm shift in that 18 (90%) patients were managed conservatively with nasal packing interpandemic. Conclusion A paradigm shift in the management of Epistaxis during the pandemic has led to treatment which is less invasive, has less morbidity for the patient, requires less hospital admissions and lessens nosocomial transmission of the Sars-CoV-2. Further study is required given the advent of vaccines and development of various strains Sars-CoV-2.

Validation of the Kinetik Blood Pressure Monitor-Series 1 for use in adults at home and in clinical settings, according to the 2002 European Society of Hypertension International Protocol on the validation of blood pressure devices.

The aim of this study was to assess the blood pressure (BP) measurement accuracy of the Kinetik Blood Pressure Monitor-Series 1 (BPM-1) for use in home or clinical settings according to the 2002 European Society of Hypertension International Protocol (ESH-IP). Forty-two participants were recruited to fulfil the required number of systolic and diastolic BP measurements according to the ESH-IP. Nine sequential same-arm BP readings were measured and analysed for each participant using the test device and observer mercury standard readings according to the 2002 ESH-IP. Forty one participants were used to obtain 33 sets of systolic and diastolic BP readings and were included in the analysis. Mean difference between the device measurements and the observer (mercury standard) measurements was 1.1 ± 7.2/1.1 ± 6.8 mmHg (mean ± standard deviation; systolic/diastolic). The number of systolic BP differences between the test and observer measurements that fell within 5, 10 and 15 mmHg was 65, 86 and 92. For diastolic readings, the number of test-observer measurement differences within 5, 10 and 15 mmHg was 77, 91 and 94. The number of participants with at least two out of three differences within 5 mmHg was 28 for systolic and 40 for diastolic BP readings. Three participants had no differences between the test and observer measurements within 5 mmHg in both the systolic and diastolic measurement categories. The Kinetik BPM-1 device fulfilled the requirements of the ESH-IP validation procedure and can be recommended for clinical use and self-measurement within the home.

A comparison between flow-regulated and adjustable valves used in hydrocephalus during infancy.

INTRODUCTION: Ventriculoperitoneal shunt insertion during the neonatal period and early infancy is associated with a high rate of shunt failure when compared to the adult population. Furthermore, the function of flow-regulated valves and differential pressure valves may be different in neonatal hydrocephalus. METHODS: A retrospective case series of all primary shunt procedures carried out during or immediately following the neonatal period, from August 2011 to February 2018 at Sheffield Children's Hospital. The total sample size was 55. This included 34 patients with adjustable valves (Miethke ProGav) and 21 with flow-regulated valves (Orbis-Sigma); however, only 53 had adequate follow-up. RESULTS: The overall 1 year shunt survival was 34% (18/53), and there was no significant difference depending on which shunt valve was implanted. The primary shunt infection rate was 11% (6/53) with S. aureus being the most common causative organism. During the first year of life, clinical signs of shunt overdrainage were seen more frequently in patients with adjustable valves than in those with flow-regulated valves (59% [19/32] versus 24% [5/21], p = 0.02). Furthermore, 2 patients in the adjustable valve group developed sagittal craniosynostosis secondary to shunt overdrainage. CONCLUSION: Shunt failure is high when inserted during or immediately following the neonatal period. Overdrainage may be less common in patients with flow-regulated valves. However, if overdrainage is observed, adjusting the setting of a differential pressure valve can effectively treat the overdrainage without the need for invasive shunt revision surgery.

Intramedullary ependymoma: long-term outcome after surgery.

BACKGROUND: Overall (OS) and progression-free survival (PFS) of patients undergoing spinal ependymoma resection has been frequently reported. Contrarily, OS and PFS of purely intramedullary ependymomas have not been clearly determined yet. METHODS: The data of 37 patients undergoing resection of an intramedullary ependymoma (IE) from January 2000 to December 2016 were analysed retrospectively. RESULTS: The mean age was 46 years. The male:female ratio was 24:13. The median duration of symptoms was 12 months. Sixty-two per cent of ependymomas were in the cervical, 24% in the thoracic, and 14% in the conus region in our series. The median volume was 1.3 ml. A syrinx was found in 49% and a cyst in 32%. GTR was achieved in 89%, STR in three (8%), and PR in one patient (3%). Median follow-up was 114 months. PFS was 87%, 82%, and 82% at 5, 10, and 15 years, respectively. OS was 97%, 88%, and 63% at 5, 10, and 15 years, respectively. There was a significant difference in PFS depending on the extent of resection and in OS depending on the pre-operative clinical status. There was no significant difference in OS and PFS regarding the other examined influencing factors. CONCLUSION: GTR resection was the most important factor influencing PFS. According to our results OS of IEs is much worse than that of spinal ependymomas. Our analysis confirms that patients with good pre-operative (McCormick grade 1 and 2) clinical status have significantly better OS than patients with McCormick grade 3 and higher.

Antibiotic overprescribing: Still a major concern.

Despite universal agreement that antibiotic overprescribing is a problem, the practice continues to vex us. Antibiotic use--whether appropriate or not--has been linked to rising rates of antimicrobial resistance, disruption of the gut microbiome leading to Clostridium difficile infections, allergic reactions, and increased health care costs. And yet, physicians continue to overprescribe this class of medication. A 2016 Centers for Disease Control and Prevention report estimates that at least 30% of antibiotics prescribed in US outpatient settings are unnecessary. Another report cites a slightly higher figure across a variety of health care settings. Pair these findings with the fact that there are currently few new drugs in development to target resistant bacteria, and you have the potential for a post-antibiotic era in which common infections could become lethal. Family practitioners are on the front lines of this battle. Here's what we can do now.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Vertebral artery and osseous anomalies characteristic at the craniocervical junction diagnosed by CT and 3D CT angiography in normal Czech population: analysis of 511 consecutive patients.

There are numerous indications for stabilization using instrumentation of the upper cervical spine. This area is comprised of sophisticated anatomy. There is no study describing bony and vascular anomalies of this area in the middle European population. The main aim of this study was to investigate prevalence of any vertebral artery (VA) variations and osseous anomalies in the region of the craniocervical junction in a large sample of Czech patients based on three-dimensional computed tomographic angiography (3D CTA). The VA has a variable course through C2 before it passes above its groove on the posterior arch of C1. The artery can course more medially, more posteriorly or more superiorly, thus limiting the diameter of the bony elements used as landmarks for the safe insertion of metalwork. This is known as a high-riding VA (HRVA). The VA was considered HRVA in this study if the thickness of the C2 isthmus was less than 5 mm and/or the C2 internal height was less than 2 mm and/or the width of the C2 pedicle was less than 4 mm. The prevalence of ponticulus posticus (PP) was also identified. Following the VA variations in the V3 segment of the artery were persistent first intersegmental artery (FIA), fenestration (FEN) of the VA, and the posterior inferior cerebellar artery (PICA) branch originating from the C1/2 part of VA. Records of 511 patients from our institution were analyzed. The mean age of the patients was 63.6 years. One hundred and twenty-three (24.1 %) patients were identified to have HRVA, 30 (6 %) present on both sides. The age of patient over 70 years and female sex were found to be significant risk factors for HRVA presence. The prevalence of a nearby PICA branch was 4 %, FIA was 0.4 %, and FEN was 0.2 %. The presence of PP was identified in 14.3 % of patients. The HRVA and PP are common anomalies in the Czech population, and routine preoperative high-resolution CT evaluation is mandatory to prevent the VA injury when C1-C2 instrumentation is planned. The female sex and age over 70 years were found to be the most important factors for HRVA presence. The FIA and the FEN VA were rare in our study contrary to reports published from Asia, showing as many as a 10 % the VA presence over the starting point for C1 lateral screw. On the basis of the infrequent occurrence of these anomalies, we do not recommend routine CT angiography when upper cervical spine instrumentation in the normal population is planned.

Eosinophil activities modulate the immune/inflammatory character of allergic respiratory responses in mice.

BACKGROUND: The importance and specific role(s) of eosinophils in modulating the immune/inflammatory phenotype of allergic pulmonary disease remain to be defined. Established animal models assessing the role(s) of eosinophils as contributors and/or causative agents of disease have relied on congenitally deficient mice where the developmental consequences of eosinophil depletion are unknown. METHODS: We developed a novel conditional eosinophil-deficient strain of mice (iPHIL) through a gene knock-in strategy inserting the human diphtheria toxin (DT) receptor (DTR) into the endogenous eosinophil peroxidase genomic locus. RESULTS: Expression of DTR rendered resistant mouse eosinophil progenitors sensitive to DT without affecting any other cell types. The presence of eosinophils was shown to be unnecessary during the sensitization phase of either ovalbumin (OVA) or house dust mite (HDM) acute asthma models. However, eosinophil ablation during airway challenge led to a predominantly neutrophilic phenotype (>15% neutrophils) accompanied by allergen-induced histopathologies and airway hyper-responsiveness in response to methacholine indistinguishable from eosinophilic wild-type mice. Moreover, the iPHIL neutrophilic airway phenotype was shown to be a steroid-resistant allergic respiratory variant that was reversible upon the restoration of peripheral eosinophils. CONCLUSIONS: Eosinophil contributions to allergic immune/inflammatory responses appear to be limited to the airway challenge and not to the sensitization phase of allergen provocation models. The reversible steroid-resistant character of the iPHIL neutrophilic airway variant suggests underappreciated mechanisms by which eosinophils shape the character of allergic respiratory responses.

Surgery of brainstem cavernous malformations.

BACKGROUND: Cavernomas are vascular hamartomas made up of thin-walled, grossly dilated blood vessels lined with endothelium. Between 4 and 35 % (mean 15 %) of cerebral cavernomas are located in the brainstem making resection of these lesions one of the most challenging tasks in neurosurgery. METHODS: Patients with cavernomas within the brainstem or deep supratentorial structures were chosen from our prospectively collected database of operated patients with brain cavernomas. The timespan of treatment was between January 1998 and June 2012. Primary outcome was defined as percentage of patients with favourable outcome (Glasgow Outcome Scale (GOS) 4 or 5) at 1 year. Secondary outcome was defined as operation-related morbidity and mortality (drop at least 1 point on GOS at 1 year). RESULTS: A total of 37 patients underwent surgery. The mean age was 34.7 ± 11.7 years. The male to female ratio was 19:16. Thirty-two patients had a solitary lesion and 12 patients harboured multiple lesions. The Glasgow outcome score 4 or 5 was achieved after 34 operations (89.5 %). The mean follow-up was 39 months. We experienced two early post-operative deaths (5.3 %) and decrease in the Glasgow outcome scale postoperatively in 4 patients (10.5 %). CONCLUSIONS: • Favourable outcome was achieved in 89.5 % of cases. • Although M&M appears to be relatively high, surgery is method of choice for surgically accessible lesion which has bled for the first time due to reported high rebleed rate and high probability of poor outcome after cavernoma rebleed. • Radiosurgery should be reserved for those lesions which are deemed unresectable and where surgical intervention is considered favourable to observation alone.

Impact of metabolic indices on central artery stiffness: independent association of insulin resistance and glucose with aortic pulse wave velocity.

AIMS/HYPOTHESIS: Non-invasive measures of aortic stiffness reflect vascular senescence and predict outcome in diabetes. Glucose-mediated elastic artery sclerosis may play an integral role in the development of macrovascular complications. We used carotid-femoral pulse wave velocity ((cf)PWV) to quantify independent associations of fasting glucose, post-challenge glucose and derived insulin resistance (HOMA-IR) with aortic stiffness. METHODS: (cf)PWV was measured using a 4 MHz continuous wave Doppler ultrasound probe within groups with newly identified age- and sex-matched normal glucose metabolism (NGM), impaired glucose regulation (IGR) and diabetes mellitus populations (n = 570, mean age 59.1, 56% male). RESULTS: After multivariate adjustment, IGR and diabetes were associated with significant aortic stiffening compared with NGM (adjusted (cf)PWV+/-SE: NGM, 9.15 +/- 0.12 m/s; IGR 9.76 +/- 0.11 m/s, p < 0.001; diabetes, 9.89 +/- 0.12 m/s, p < 0.001). IGR stratification indicated that impaired fasting glucose (IFG; 9.71 +/- 0.12 m/s) and post-challenge (impaired glucose tolerance; 9.82 +/- 0.24 m/s) categories had similar (cf)PWV (p = 0.83). Modelled predictors of (cf)PWV were used to assess independent metabolic associations with arterial stiffness. Fasting glucose concentration (beta = 0.10; 95% CI 0.05, 0.18; p = 0.003), 2 h post-challenge glucose (beta = 0.14; 95% CI 0.02, 0.23; p < 0.001) and HOMA-IR (beta = 0.20, 95% CI 0.05, 0.53; p < 0.001) were independently related to (cf)PWV after adjustment for age, sex, mean arterial pressure, heart rate, body mass index, renal function and antihypertensive medication. CONCLUSIONS/INTERPRETATION: IGR characterised by fasting or post-challenge hyperglycaemia is associated with significant vascular stiffening. Post-challenge glucose and HOMA-IR are the most powerful metabolic predictors of arterial stiffness, implying hyperglycaemic excursion and insulin resistance play important roles in the pathogenesis of arteriosclerosis.

Optimization of Babesia bovis transfection methods.

The tick borne Babesia parasites remain an important limitation for development of cattle industries worldwide. A stable transfection of Babesia bovis will be useful for functional analysis of the recently sequenced B. bovis genome and to design improved methods to control Babesia infections. In this study, we describe a novel system for nucleofection of B. bovis infected erythrocytes and we optimize methods to introduce plasmids encoding the luciferase reporter gene into Babesia infected erythrocytes or free merozoites using either a BioRad GenePulser II electroporation system or nucleofection technology (Amaxa) A comparative study among four different transfection methods: transfection of infected erythrocytes and purified merozoites with 2 or 100 microg of plasmid, using electroporation (BioRad GenePulser II) or nucleofection (Amaxa) indicates that electroporation of infected erythrocytes with 100 microg of plasmid or nucleofection with 2 microg of plasmid are the most efficient ways to transfect B. bovis parasites. The data also indicate that nucleofection is more efficient than electroporation for transfecting small quantities of plasmids (2 microg range), whereas the inverse is true for transfection of larger quantities (100 microg range). This information will facilitate further development of efficient stable transfection systems.

A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils.

BACKGROUND: Granulocyte exocytosis is proposed to be critically dependent on the interaction of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs) located on granules/vesicles (v-SNAREs) and plasma membrane (t-SNAREs). Previous studies indicated that the v-SNARE, vesicle-associated membrane protein (VAMP)-2, as well as t-SNAREs (SNAP-23, syntaxin-4 and -6) are implicated in exocytosis from human granulocytes. Vesicle-associated membrane proteins-7 and -8 have been implicated in endosome/lysosome trafficking, however, their role in granulocyte exocytosis remains obscure. OBJECTIVE: We sought to investigate the expression and functional role of SNARE isoforms in the secretion of different granule-derived mediators in human eosinophils and neutrophils. METHODS: The expression of SNAREs was determined by subcellular fractionation and flow cytometry. SNARE-specific antibodies were examined for their ability to impair mediator release from permeabilized eosinophils and neutrophils. RESULTS: Vesicle-associated membrane proteins-7 and -8 were localized to granule and membrane-enriched fractions in eosinophils and neutrophils, whereas syntaxin-6 was not detectable. In permeabilized cells, anti-VAMP-7, but not anti-VAMP-8, antibody impaired the secretion of all mediators examined (in eosinophils, eosinophil peroxidase and eosinophil-derived neurotoxin; in neutrophils, myeloperoxidase, lactoferrin and matrix metalloprotease-9) in a dose-dependent manner. In contrast, anti-VAMP-2 modestly and selectively impaired secretion from small granules and vesicles. Syntaxin-4, but not syntaxin-6, was found to interact with SNAP-23 and was partially involved in mediator secretion from multiple compartments. CONCLUSION: Our observations indicate for the first time a critical role for VAMP-7 in both eosinophil and neutrophil mediator release.

Telomere attrition and accumulation of senescent cells in cultured human endothelial cells.

The human umbilical vein endothelial cell (HUVEC) is an important model of the human endothelium that is widely used in vascular research. HUVECs and the adult endothelium share many characteristics including progression into senescence as the cells age. Despite this, the shortening of telomeres and its relationship to the progression into senescence are poorly defined in HUVECs. In this study of several HUVEC lines we show notable consistency in their growth curves. There is a steady decline in the growth rate of HUVECs grown continually in culture and we estimate complete cessation of growth after approximately 70 population doublings. The HUVECs lose telomeric DNA at a consistent rate of 90 base pairs/population doubling and show a progressive accumulation of shortened telomeres (below 5 kilobases). This telomeric loss correlates with the accumulation of senescent HUVECs in culture as assessed by staining for beta-galactosidase activity at pH 6. Although the telomere length of a large population of cells is a relatively crude measure, we suggest that in HUVECs a mean telomere length (as measured by terminal restriction fragment length) of 5 kilobases is associated with entry into senescence. These data demonstrate the strong relationship between telomere attrition and cell senescence in HUVECs. They suggest that DNA damage and subsequent telomere attrition are likely to be key mechanisms driving the development of endothelial senescence in the pathogenesis of vascular disease.

Massive subcutaneous emphysema following routine endotracheal intubation.

Upper aerodigestive tract injury after endotracheal intubation is a rare but serious complication. The case of a 57-year-old female, who developed extensive neck and pneumomediastinum following a knee arthroscopy under general anaesthesia, is presented. Possible mechanisms of injury and management options are discussed.

High resolution computed tomography and magnetic resonance imaging in the pre-operative assessment of cochlear implant patients.

Optimal imaging protocols for cochlear implantation have yet to be determined. Pre-operative computed tomography (CT) and magnetic resonance image (MRI) scans are used to assess cochlear anatomy and patency, to delineate surgical access, and to aid in choice of side for implantation. However, opinion still differs as to which modality provides more information in pre-operative assessment, or if, indeed, a combination of the two is superior. The first 88 patients on the Irish National Cochlear Implant Programme (NCIP) were retrospectively studied to determine the accuracy of pre-operative CT and MRI in predicting abnormalities at the time of surgery. Correlation with surgical findings was determined in three separate groups of patients (those who had CT only, those who had MRI only, and those who had both CT and MRI performed). Of the 24 patients that had both CT and MRI performed, both modalities had a 79 per cent correlation with surgical findings. CT and MRI reports concurred in 75 per cent of cases. Specificity and negative predictive value were high (86 per cent and 90 per cent, respectively). CT alone (47 cases) correlated with surgery in 39 cases (83 per cent); MRI alone (17 cases) correlated in 15 cases (88 per cent). The findings of this study suggest that CT and MRI are effective at predicting normal inner ear anatomy, and thus at predicting the patient and the cochlea most suitable for implantation. Both modalities are useful in determining the side of implantation, thus avoiding potential surgical difficulties in cases of unilateral abnormalities. There was no significant difference between the ability of MRI and CT to detect abnormalities at the time of surgery. In this series the combination of CT and MRI has not been shown to be superior to either modality used alone, although anecdotal evidence to the contrary was noted.