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.

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.

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.

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.

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.

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.

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.

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.

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.

Duplex carotid sonography. Peak systolic velocity in quantifying internal carotid artery stenosis.

Duplex ultrasonography combining high-resolution imaging and Doppler spectrum analysis was performed in 92 consecutive patients (total, 180 vessels) and compared with the findings of conventional arteriography. All duplex studies were categorized into four groups based upon the maximum internal carotid artery (ICA) velocity: group 1: less than 125 cm/sec; group 2: 125 to 224 cm/sec; group 3: greater than 225 cm/sec; and group 4: no flow. Sensitivities and specificities were highest when peak ICA velocity was used as one of several criteria in quantifying the degree of ICA stenosis. These additional criteria were: (1) the presence of extensive sonographically visible plaque within the ICA; (2) an abnormal spectral waveform with elevated diastolic velocity (greater than 100 cm/sec); (3) resistive pattern ("externalization") of the common carotid artery (CCA) waveform; and (4) the ratio of the right CCA peak velocity to the left of less than 0.7 or greater than 1.3. The overall accuracy for the combined groups using all criteria was 94%.

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.

Replaced or right accessory hepatic artery: can ultrasound replace angiography?

The accuracy of ultrasonography in detecting the right hepatic artery was prospectively assessed in 128 patients undergoing abdominal angiography. Twenty-five (19%) of the ultrasound studies were technically inadequate mainly because of gas superimposition. Of the remaining 103 cases, 14 had a replaced hepatic artery, which was diagnosed in 10 cases with ultrasound (sensitivity 71%). Eighty-nine did not have a replaced hepatic artery and the ultrasound assessment was falsely positive in four of them (specificity 96%). Two of the four false negative results could be explained by a stenosis of the superior mesenteric artery in front of the origin of the replaced hepatic artery. Two of the four false positive results could be explained by the presence of a stenosis of the celiac trunk with hypertrophy of the pancreaticoduodenal arteries, one of them being misdiagnosed as a replaced hepatic artery.

Gallbladder and bile duct abnormalities in AIDS: sonographic findings in eight patients.

Gallbladder and biliary tract abnormalities were observed on sonography in eight patients with AIDS. The studies were obtained to evaluate right upper quadrant pain (two patients), tenderness (three patients), and abnormal liver function tests (eight patients). The two major sonographic findings were gallbladder wall thickening (eight patients), which often was marked, and bile duct dilatation (two patients). Gallbladder wall thickness varied from 4 to 15 mm and was greater than 1 cm in four patients. Follow-up sonograms in five patients showed increasing wall thickness in four and decreasing thickness in one, but these findings did not correlate well with the clinical status of the patient. Pericholecystic fluid was shown in three cases. None of the patients had gallstones. Common bile duct dilatation varied from 12 to 15 mm; no specific cause for dilatation was found by cholangiography. Mycobacterium avium intracellulare was recovered from the gallbladder in one patient, and Cryptosporidium was recovered from the duodenum in two patients. AIDS should be considered in the differential diagnosis of gallbladder wall thickening or bile duct dilatation in the appropriate clinical setting. These findings may indicate opportunistic infection of the biliary tract. A disparity may exist between the mild symptoms and signs (or lack of symptoms and signs) related to the gallbladder and bile ducts and the sometimes marked sonographic abnormalities.

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.