We describe a retrospective study of 4 cases of sporadic fatal infectious mononucleosis (IM), 1 case of fatal IM, and 1 case of sporadic severe IM. Patients were 26 months to 17 years old; 3 were ...male. Five died of complications of IM. All 5 of these patients had the Epstein-Barr virus (EBV) present in examined tissue specimens; EBV was monoclonal in 3 patients and biclonal in 1. EBV clonality studies were not performed in the remaining patient. All 5 patients also had monoclonal gene rearrangements. The sixth patient survived despite a life-threatening clinical course; EBV was oligoclonal, and gene rearrangements were not detected. EBV clonality and gene rearrangement studies may be usefulfor predicting which patients with clinically aggressive IM are at highest risk for fatal outcome. Patients in whom IM has a fatal outcome are more likely to have monoclonal or biclonal EBV and immunoglobulin heavy chain or T-cell receptor gene rearrangements. In contrast, patients with nonfatal IM may lack monoclonal EBV and monoclonal rearrangements of the aforementioned genes. The reasons EBV induces a monoclonal proliferation only in some patients remain to be elucidated.
Background/Purpose: Coronavirus disease 2019 (COVID-19) is associated with increased risk of acute ischemic stroke (AIS), however, there is a paucity of data regarding outcomes after administration ...of intravenous tissue plasminogen activator (IV tPA) for stroke in patients with COVID-19.
Methods: We present a multicenter case series from 9 centers in the United States of patients with acute neurological deficits consistent with AIS and COVID-19 who were treated with IV tPA.
Results: We identified 13 patients (mean age 62 (±9.8) years, 9 (69.2%) male). All received IV tPA and 3 cases also underwent mechanical thrombectomy. All patients had systemic symptoms consistent with COVID-19 at the time of admission: fever (5 patients), cough (7 patients), and dyspnea (8 patients). The median admission NIH stroke scale (NIHSS) score was 14.5 (range 3–26) and most patients (61.5%) improved at follow up (median NIHSS score 7.5, range 0–25). No systemic or symptomatic intracranial hemorrhages were seen. Stroke mechanisms included cardioembolic (3 patients), large artery atherosclerosis (2 patients), small vessel disease (1 patient), embolic stroke of undetermined source (3 patients), and cryptogenic with incomplete investigation (1 patient). Three patients were determined to have transient ischemic attacks or aborted strokes. Two out of 12 (16.6%) patients had elevated fibrinogen levels on admission (mean 262.2 ± 87.5 mg/dl), and 7 out of 11 (63.6%) patients had an elevated D-dimer level (mean 4284.6 ±3368.9 ng/ml).
Conclusions: IV tPA may be safe and efficacious in COVID-19, but larger studies are needed to validate these results.
The objectives of this study were to assess if targeted investigation for tumor-specific mutations by ultradeep DNA sequencing of peritoneal washes of ovarian cancer patients after primary surgical ...debulking and chemotherapy, and clinically diagnosed as disease free, provides a more sensitive and specific method to assess actual treatment response and tailor future therapy and to compare this "molecular second look" with conventional cytology and histopathology-based findings.
We identified 10 patients with advanced-stage, high-grade serous ovarian cancer who had undergone second-look laparoscopy and for whom DNA could be isolated from biobanked paired blood, primary and recurrent tumor, and second-look peritoneal washes. A targeted 56 gene cancer-relevant panel was used for next-generation sequencing (average coverage, >6500×). Mutations were validated using either digital droplet polymerase chain reaction (ddPCR) or Sanger sequencing.
A total of 25 tumor-specific mutations were identified (median, 2/patient; range, 1-8). TP53 mutations were identified in at least 1 sample from all patients. All 5 pathology-based second-look positive patients were confirmed positive by molecular second look. Genetic analysis revealed that 3 of the 5 pathology-based negative second looks were actually positive. In the 2 patients, the second-look mutations were present in either the original primary or recurrent tumors. In the third, 2 high-frequency, novel frameshift mutations in MSH6 and HNF1A were identified.
The molecular second look detects tumor-specific evidence of residual disease and provides genetic insight into tumor evolution and future recurrences beyond standard pathology. In the precision medicine era, detecting and genetically characterizing residual disease after standard treatment will be invaluable for improving patient outcomes.
The time course of the ventricular fibrillation threshold (VFT) was studied in 10 open-chest mongrel dogs following acute occlusion of the left anterior descanding coronary artery (LAD). The VFT in ...the infarcted area was compared to a non-infarcted area of the left ventricle supplied by the circumflex coronary artery. Prior to coronary occlusion the mean VFT for the entire group of 10 animals was 14 ma. for the area supplied by the LAD and 17.6 ma. for the area of the left circumflex. Immediately after coronary ligation the VFT decreased in both areas. Within 90 to 120 minutes the VFT in the infarcted area was 27 ma. and after 6 hours of occlusion the VFT was 3 times the pre-ligation value. The VFT in the non-infarcted area remained near the pre-ligation values. The excitability of the infarcted area was markedly decreased after coronary occlusion and this accounted for the increase in the VFT in the infarcted area. In the non-ischemic area the excitability was unchanged during the entire six hour period following occlusion. The study stresses the importance of the location of the electrodes used for fibrillation and the natural course of the VFT in evaluating VFT's within the ischemic myocardium.
The threshold for ventricular fibrillation induced by a 200 msec train of pulses was measured during a control period and during an intravenous infusion of nitroglycerin in 14 nonischemic open chest ...dogs. Infusion of nitroglycerin in doses sufficient to reduce mean arterial blood pressure an average of 17 mm Hg was associated with a rise in ventricular fibrillation threshold from a control value of 24 +/- 3 (mean +/- 1 standard error of the mean) to 41 +/- 6 milliamperes (P less than 0.001). In a subgroup of six animals simultaneous infusions of nitroglycerin and phenylephrine abolished the hypotensive effect of nitroglycerin but did not significantly alter the rise in ventricular fibrillation threshold observed with nitroglycerin infusion alone. In five other animals mean arterial blood pressure was similarly reduced an average of 17 mm Hg by venous hemorrhage, but was associated with a lowering than a rise in ventricular fibrillation threshold from a prehemorrhage value of 28 +/- 6 to 15 +/- 2 milliamperes, (P less than 0.005). Thus, intravenously administered nitroglycerin raises ventricular fibrillation threshold in nonischemic canine myocardium independent of its hypotensive effects.
We used direct invasive techniques to measure the effects of hyperventilation on the pulmonary blood flow (Q) and on recirculation time of helium and of carbon dioxide in humans. The subjects ...hyperventilated with a tidal volume of 1.5 liters (BTPS) and a frequency of 20 or 30 breaths/min. There was no significant change in Q from control at either level of hyperventilation. Helium first appeared in the pulmonary artery within 12 s from the onset of hyperventilation and increased by approximately 0.7% of its equilibrium arterial value per second at both levels of hyperventilation. In contrast, the PVCO2 remained at base-line level until 43 s from the onset of hyperventilation. We conclude that hyperventilation at 30 or 45 l/min with constant tidal volume does not significantly affect the value of Q and that the amount of recirculation of the two gases does not result in underestimation of Q when this variable is measured by indirect respiratory rebreathing techniques.
Ten patients with roentgenographically demonstrable mitral annulus calcification (MAC) were found to have distinctive echocardiographic patterns. MAC was confirmed at the time of cardiac ...catheterization in six of these patients. Standard M-mode echocardiograms revealed a dense band of echoes in the region of the mitral annulus in contrast to the thin and delicate echoes generally recorded from the normal mitral annulus. Intraoperative and pathologic confirmation of thickening and calcification limited to the mitral annulus was made in two patients who underwent mitral valve replacement for severe mitral regurgitation due to myxamatous "floppy" valve. Patients with marked MAC may have coexisting aortic valve or papillary muscle calcification which can be recognized by echocardiography. Over-attenuation of left ventricular wall echoes in patients with marked MAC, and reduction in E-F slope of the anterior mitral valve leaflet in others can simulate pericardial effusion and mitral stenosis, respectively. Thus, recognition of MAC can avoid confusion with similar echocardiographic patterns due to other common cardiac abnormalities.
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