Interictal discharges in the human brain are travelling waves arising from an epileptogenic source.

While seizure activity may be electrographically widespread, increasing evidence has suggested that ictal discharges may in fact represent travelling waves propagated from a focal seizure source. Interictal epileptiform discharges (IEDs) are an electrographic manifestation of excessive hypersynchronization of cortical activity that occur between seizures and are considered a marker of potentially epileptogenic tissue. The precise relationship between brain regions demonstrating IEDs and those involved in seizure onset, however, remains poorly understood. Here, we hypothesize that IEDs likewise reflect the receipt of travelling waves propagated from the same regions which give rise to seizures. Forty patients from our institution who underwent invasive monitoring for epilepsy, proceeded to surgery and had at least one year of follow-up were included in our study. Interictal epileptiform discharges were detected using custom software, validated by a clinical epileptologist. We show that IEDs reach electrodes in sequences with a consistent temporal ordering, and this ordering matches the timing of receipt of ictal discharges, suggesting that both types of discharges spread as travelling waves. We use a novel approach for localization of ictal discharges, in which time differences of discharge receipt at nearby electrodes are used to compute source location; similar algorithms have been used in acoustics and geophysics. We find that interictal discharges co-localize with ictal discharges. Moreover, interictal discharges tend to localize to the resection territory in patients with good surgical outcome and outside of the resection territory in patients with poor outcome. The seizure source may originate at, and also travel to, spatially distinct IED foci. Our data provide evidence that interictal discharges may represent travelling waves of pathological activity that are similar to their ictal counterparts, and that both ictal and interictal discharges emerge from common epileptogenic brain regions. Our findings have important clinical implications, as they suggest that seizure source localizations may be derived from interictal discharges, which are much more frequent than seizures.

Identifying sources of human interictal discharges with travelling wave and white matter propagation.

Interictal epileptiform discharges have been shown to propagate from focal epileptogenic sources as travelling waves or through more rapid white matter conduction. We hypothesize that both modes of propagation are necessary to explain interictal discharge timing delays. We propose a method that, for the first time, incorporates both propagation modes to identify unique potential sources of interictal activity. We retrospectively analysed 38 focal epilepsy patients who underwent intracranial EEG recordings and diffusion-weighted imaging for epilepsy surgery evaluation. Interictal discharges were detected and localized to the most likely source based on relative delays in time of arrival across electrodes, incorporating travelling waves and white matter propagation. We assessed the influence of white matter propagation on distance of spread, timing and clinical interpretation of interictal activity. To evaluate accuracy, we compared our source localization results to earliest spiking regions to predict seizure outcomes. White matter propagation helps to explain the timing delays observed in interictal discharge sequences, underlying rapid and distant propagation. Sources identified based on differences in time of receipt of interictal discharges are often distinct from the leading electrode location. Receipt of activity propagating rapidly via white matter can occur earlier than more local activity propagating via slower cortical travelling waves. In our cohort, our source localization approach was more accurate in predicting seizure outcomes than the leading electrode location. Inclusion of white matter in addition to travelling wave propagation in our model of discharge spread did not improve overall accuracy but allowed for identification of unique and at times distant potential sources of activity, particularly in patients with persistent postoperative seizures. Since distant white matter propagation can occur more rapidly than local travelling wave propagation, combined modes of propagation within an interictal discharge sequence can decouple the commonly assumed relationship between spike timing and distance from the source. Our findings thus highlight the clinical importance of recognizing the presence of dual modes of propagation during interictal discharges, as this may be a cause of clinical mislocalization.

Potential sources of mouth drying in beverages fortified with dairy proteins: A comparison of casein- and whey-rich ingredients.

Oral nutritional supplement drinks (ONS) are beverages high in dairy proteins that are prescribed to individuals at risk of malnutrition. Consumption of ONS is poor in elderly care facilities, with patients commenting that the sensory attributes of these drinks reduce their enjoyment and willingness to consume. Mouth drying is an attribute of ONS found to build with repeated consumption, which may further limit liking of these products. This study investigated the sources of drying sensations by sequential profiling, with a trained sensory panel rating a range of model milk systems and ONS over repeated sips and during after-effects. Sequential profiling found that fortification of milk with both caseinate and whey protein concentrate significantly increased the perception of mouth drying over repeated consumption, increasing by between 35 and 85% over consumption of 40mL. Enrichment of ONS with either whey protein concentrate or milk protein concentrate to a total protein content of 8.7% (wt/wt) resulted in whey and casein levels of 4.3:4.4% and 1.7:7.0% respectively. The product higher in whey protein was substantially more mouth drying, implying that whey proteins may be the most important contributor to mouth drying in ONS. However, efforts to mask mouth drying of protein-fortified milk by increasing sweetness or fat level were unsuccessful at the levels tested. Increasing the viscosity of protein-fortified milk led to a small but significant reduction in mouth drying. However, this approach was not successful when tested within complete ONS. Further analysis is required into the mechanism of protein-derived mouth drying to mask negative sensations and improve the enjoyment and consumption of protein-rich ONS.

Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is commonly used for respiratory failure due to severe COVID-19 pneumonitis, including in patients deemed not likely to benefit from invasive mechanical ventilation (nIMV). Little evidence exists demonstrating superiority over conventional oxygen therapy, whilst ward-level delivery of CPAP presents practical challenges. We sought to compare clinical outcomes of oxygen therapy versus CPAP therapy in patients with COVID-19 who were nIMV. METHODS: This retrospective multi-centre cohort evaluation included patients diagnosed with COVID-19 who were nIMV, had a treatment escalation plan of ward-level care and clinical frailty scale ≤ 6. Recruitment occurred during the first two waves of the UK COVID-19 pandemic in 2020; from 1st March to May 31st, and from 1st September to 31st December. Patients given CPAP were compared to patients receiving oxygen therapy that required FiO2 ≥0.4 for more than 12 hours at hospitals not providing ward-level CPAP. Logistic regression modelling was performed to compare 30-day mortality between treatment groups, accounting for important confounders and within-hospital clustering. FINDINGS: Seven hospitals provided data for 479 patients during the UK COVID-19 pandemic in 2020. Overall 30-day mortality was 75.6% in the oxygen group (186/246 patients) and 77.7% in the CPAP group (181/233 patients). A lack of evidence for a treatment effect persisted in the adjusted model (adjusted odds ratio 0.84 95% CI 0.57-1.23, p=0.37). 49.8% of patients receiving CPAP-therapy (118/237) chose to discontinue it. INTERPRETATION: No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the current treatment guidance and widespread application of CPAP in this setting. FUNDING: L Pearmain is supported by the MRC (MR/R00191X/1). TW Felton is supported by the NIHR Manchester Biomedical Research Centre.

Characterization of phosphorus sources in rural watersheds.

Correct identification of P sources in rural watersheds is critical for the development of cost-effective measures to combat agriculturally-driven eutrophication. The chemical composition of various storm runoff types (field surface runoff, field drain outfalls, roads, farmyards, and septic tanks) and the receiving streams in three micro (<10 km(2)) watersheds of varying agricultural intensity were monitored over a 2-yr period. Mean weekly stream soluble reactive phosphorus (SRP) and total phosphorus (TP) concentrations increased from 29 and 69 microg L(-1), respectively in the watershed with the lowest intensity agriculture to 382 and 503 microg L(-1), respectively in the watershed with high intensity agriculture and a village sewage treatment works. Concentrations of TP in storm runoff varied by up to two orders of magnitude reflecting the complex origins, routing, and composition of contributing source areas. Application of the DESPRAL test suggested field runoff TP concentrations were influenced by both P and organic matter in soil. However, runoff from impervious surfaces (farmyard and roads), and/or influenced by septic tank discharges, was significantly more concentrated (0.08-16 mg TP L(-1), mean >>1 mg L(-1)) than surface and subsurface runoff from cultivated land and pasture (0.02-3.6 mg TP L(-1), mean <1 mg L(-1)), and/or contained a significantly greater proportion (>50% vs. <50%) of P in dissolved forms. It is concluded that P sources associated with the functioning of rural communities (impervious surfaces, detergents, and wastewater) may be more ecologically relevant than those associated with agriculture and should be better quantified and controlled to avoid localized eutrophication impacts.

Effect of propionic acid on urea synthesis by sheep liver.

Propionate reduced substantially the rate of ureagenesis by slices of sheep liver whereas butyrate did not inhibit urea synthesis. The site of inhibition of urea synthesis by propionate occurs at some point between the fixation of ammonia and the formation of citrulline since 0.5 mM propionate inhibited by 80 per cent the synthesis of citrulline by mitochondria isolated from sheep liver. Since the apparent Ki for propionate is approximately 1.7 mM, the inhibitory effect of propionate on urea synthesis could be of physiological significance in sheep.

Developing multidisciplinary profiles in a day hospital.

The Ferguson Day Hospital provides a patient-centred, multidisciplinary service for patient assessment and rehabilitation. The authors describe the development of a patient profile that has centralised documentation and reflects the multidisciplinary nature of the services provided.

Electronic voicemail: one hospital's experience.

Children's Hospital of Wisconsin's electronic voicemail system has not only saved time and energy, but also delivered user satisfaction. This demonstrates that this communications technology is an absolutely essential component of an effective communications network in a hospital.

Gaucher's disease involving the spleen.

Gaucher's disease is a rare inherited disorder that results from progressive accumulation of glucocerebrosides within the reticuloendothelial system and affects the liver, the spleen, the bone marrow and the lymph nodes. Ultrasonography of the spleen typically demonstrates hypoechoic focal masses; however, the lesions may be hyperechoic if they contain extensive fibrosis or infarction. The authors describe a young Ashkenazi man who presented with splenomegaly as the single clinical manifestation and in whom were found splenic masses of mixed echogenicity, none of which demonstrated fibrosis or infarction when studied pathologically.

The air-filled left hepatic duct: the saber sign as an aid to the radiographic diagnosis of pneumobilia.

In the supine patient, gas rises to the left hepatic duct. Radiographically, this can be recognized as a saber-shaped lucency to the right of the spine. In a retrospective analysis and review of the radiographs of 40 patients shown to have gas in the biliary tree by ultrasound (US), computed tomography (CT), or radiography, the diagnosis could be made in 37 patients. In 18 of these 37 cases pneumobilia could be identified by the saber-shaped distribution of gas. Knowledge of the medial distribution of biliary gas in the supine patient and appreciation of the saber sign can increase the sensitivity of the radiographic detection of pneumobilia.

Value of standardized gestational age charts for fetuses of first-generation Oriental immigrants to Canada.

OBJECTIVE: to ascertain if standard gestational age charts can be used to accurately predict the gestational age of fetuses of first-generation Oriental immigrants to Canada. PATIENTS AND METHODS: Over a 3-year period, all patients presenting for obstetric ultrasound examinations were invited to participate in the study. The authors recorded biparietal diameter, head circumference, femur length and abdominal circumference for 139 fetuses in the second and third trimesters. A study performed in the first trimester was used as the baseline for gestational age. The data for 126 of the fetuses were complete, and these data were used for the analysis. RESULTS: For 77 of the fetuses, both parents were Oriental, and for 49, one or both parents were not Oriental; the latter constituted the control group. A total of 1008 individual measurements were obtained, and of these, all but 14 fell within two standard deviations of the norm, according to standard gestational age charts. Of the abnormal measurements, seven were obtained from five fetuses with Oriental parents, and seven were obtained from six fetuses in the control group. The difference between the two groups in the proportion of measurements falling either above or below two standard deviations from the norm was not statistically significant (Fisher's exact test, p = 0.41694). CONCLUSION: The authors conclude that standard gestational age charts can be used to determine gestational age in first-generation Oriental immigrants to Canada.

Pneumothorax: radiologic treatment with small catheters.

In many institutions, the standard treatment of symptomatic and large pneumothoraxes has been with surgically placed large-bore (22-32-F) chest tubes. During the past 3-4 years, the authors used small catheters (7, 8.2, and 9.4 F) to decompress 30 pneumothoraxes (15 under tension) resulting from percutaneous lung biopsy. The catheters were inserted under computed tomographic or fluoroscopic guidance for the treatment of large (greater than 35%) or symptomatic pneumothoraxes. Twenty-eight of 30 patients were treated successfully with the small catheters alone; two patients underwent surgical placement of 32-F tubes (4 and 12 hours later) because of incomplete resolution of the pneumothoraxes. This series demonstrates that small-caliber catheters effectively decompress pneumothoraxes and that they can be inserted expeditiously by radiologists in the radiology department.

Intravascular tumors: transvenous biopsy.

A technique is described for transfemoral biopsy of intravenous tumors. Positive results were obtained at biopsy in three patients who had an intraluminal mass in the inferior vena cava and in one patient with a mass in the iliac vein. Transvenous biopsy is helpful in obtaining a histologic diagnosis and provides an alternative method to surgery or percutaneous transabdominal needle biopsy.

Role of intraoperative ultrasonography in hepatic surgery: a preliminary report.

Twenty-four patients who underwent ultrasonography during hepatic surgery in the 22 months from October 1989 to July 1991 were studied prospectively to determine the value, if any, of intraoperative ultrasonography. For 6 (25%) of the 24 patients the operative plan was altered because of the ultrasonographic findings. In one of them resection was extended from a left lateral segmentectomy or sectorectomy to a left hemihepatectomy. In the other five patients the planned liver procedure was abandoned. Two of these five patients were cirrhotic--in one of them an additional metastasis was seen, and in the other there was tumour invasion of the portal vein. Of the three noncirrhotic patients, one had tumour invasion of the right hepatic vein, and the other two patients had additional metastases in the caudate lobe (Couinaud segment 1). Ultrasonography was found to be useful in 25% of patients who underwent this investigation during hepatic surgery--it avoided liver resections that would have failed because of advanced malignant disease.

Unsuspected pheochromocytoma: risk of blood-pressure alterations during percutaneous adrenal biopsy.

Four unsuspected pheochromocytomas were discovered during percutaneous fine-needle biopsy of the adrenal gland under ultrasound (n = 1) and computed tomographic (n = 3) guidance. One patient suffered an acute episode of alternating hypertension and hypotension during the procedure. A second patient had no alterations in vital signs during the procedure but had a severe hypertensive crisis during induction of anesthesia at surgery. Neither biopsy nor surgery affected the vital signs in the other two patients. During biopsy study of adrenal lesions, the possibility of unsuspected pheochromocytoma should be considered, and the interventional radiologist must be familiar with the emergency treatment of hypotensive or hypertensive crises that may occur.

Lymphoceles: imaging characteristics and percutaneous management.

Twenty-five patients who had lymphoceles underwent sectional imaging and interventional radiologic procedures. Viewed using sonography, lymphoceles were hypoechoic to anechoic, occasionally with internal septa and debris. Low numbers (occasionally negative values) were observed using computed tomography (CT); these numbers strongly suggest the diagnosis of lymphocele. Calcification was observed on CT images of one patient. Diagnostic aspiration revealed tan to yellow fluid containing many lymphocytes; pathognomonic fat globules were observed in four cases. Malignant cells were found in two collections, an unusual occurrence. Therapeutic needle aspiration and short-term catheter drainage were usually unsuccessful (only one of five patients [20%] was cured). Long-term (1-5-week) catheter drainage cured 11 of 14 patients (78.6%). Sclerosing agents may have been beneficial for lymphocele obliteration in three of four patients. For most patients, lymphoceles may be diagnosed and treated successfully using radiologic means.

Percutaneous cecostomy for decompression of the massively distended cecum.

Massive dilatation of the cecum developed in an elderly man following admission for an acute episode of upper gastrointestinal hemorrhage complicated by myocardial infarction, ventricular fibrillation, and pulmonary edema. A diagnosis of pseudo-obstruction was made. After an unsuccessful attempt at colonoscopy, percutaneous cecostomy was performed under computed tomographic guidance, using trocar technique. The cecal distention resolved and did not recur. Percutaneous cecostomy is an alternative to colonoscopy and to surgical cecostomy in the treatment of massive cecal distention.

Abscesses in Crohn disease: percutaneous drainage.

Fifteen patients with Crohn disease underwent percutaneous catheter drainage of related abdominal abscesses. The abscesses were located in the right lower quadrant (five patients); in the quadratus lumborum and/or iliopsoas muscles (four patients); in the left paracolic gutter (two patients); and in the right gluteal muscles, the liver, the left subphrenic space, and the pelvis (one patient each). All abscesses were evacuated successfully (n = 15 of 15), and no patient required surgery for abscess drainage. Existing fistulas closed in four of seven patients; the other three patients underwent surgery for excision of diseased bowel and enteric fistulas. No patient developed an enterocutaneous fistula as a result of catheter drainage. Percutaneous abscess drainage is effective for abscesses related to Crohn disease and should be regarded as the procedure of choice. An operation for the abscess can be avoided, and early results suggest that bowel surgery may be obviated in selected patients.