New Insights in the Occurrence of Venous Thromboembolism in Critically Ill Patients with COVID-19-A Large Postmortem and Clinical Analysis.

Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41-4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.

Mechanical ventilation and mortality among 223 critically ill patients with coronavirus disease 2019: A multicentric study in Germany.

BACKGROUND: There are large uncertainties with regard to the outcome of patients with coronavirus disease 2019 (COVID-19) and mechanical ventilation (MV). High mortality (50-97%) was proposed by some groups, leading to considerable uncertainties with regard to outcomes of critically ill patients with COVID-19. OBJECTIVES: The aim was to investigate the characteristics and outcomes of critically ill patients with COVID-19 requiring intensive care unit (ICU) admission and MV. METHODS: A multicentre retrospective observational cohort study at 15 hospitals in Hamburg, Germany, was performed. Critically ill adult patients with COVID-19 who completed their ICU stay between February and June 2020 were included. Patient demographics, severity of illness, and ICU course were retrospectively evaluated. RESULTS: A total of 223 critically ill patients with COVID-19 were included. The majority, 73% (n = 163), were men; the median age was 69 (interquartile range = 58-77.5) years, with 68% (n = 151) patients having at least one chronic medical condition. Their Sequential Organ Failure Assessment score was a median of 5 (3-9) points on admission. Overall, 167 (75%) patients needed MV. Noninvasive ventilation and high-flow nasal cannula were used in 31 (14%) and 26 (12%) patients, respectively. Subsequent MV, due to noninvasive ventilation/high-flow nasal cannula therapy failure, was necessary in 46 (81%) patients. Renal replacement therapy was initiated in 33% (n = 72) of patients, and owing to severe respiratory failure, extracorporeal membrane oxygenation was necessary in 9% (n = 20) of patients. Experimental antiviral therapy was used in 9% (n = 21) of patients. Complications during the ICU stay were as follows: septic shock (40%, n = 90), heart failure (8%, n = 17), and pulmonary embolism (6%, n = 14). The length of ICU stay was a median of 13 days (5-24), and the duration of MV was 15 days (8-25). The ICU mortality was 35% (n = 78) and 44% (n = 74) among mechanically ventilated patients. CONCLUSION: In this multicentre observational study of 223 critically ill patients with COVID-19, the survival to ICU discharge was 65%, and it was 56% among patients requiring MV. Patients showed high rate of septic complications during their ICU stay.

Accuracy of High-Field Intraoperative MRI in the Detectability of Residual Tumor in Glioma Grade IV Resections.

Objective To assess the sensitivity/specificity of tumor detection by T1 contrast enhancement in intraoperative MRI (ioMRI) in comparison to histopathological assessment as the gold standard in patients receiving surgical resection of grade IV glioblastoma. Materials and Methods 68 patients with a primary or a recurrent glioblastoma scheduled for surgery including fluorescence guidance and neuronavigation were included (mean age: 59 years, 26 female, 42 male patients). The ioMRI after the first resection included transverse FLAIR, DWI, T2-FFE and T1 - 3 d FFE +/- GD-DPTA. The second resection was performed whenever residual contrast-enhancing tissue was detected on ioMRI. Resected tissue samples were histopathologically evaluated (gold standard). Additionally, we evaluated the early postoperative MRI scan acquired within 48 h post-OP for remaining enhancing tissue and compared them with the ioMRI scan. Results In 43 patients ioMRI indicated residual tumorous tissue, which could be confirmed in the histological specimens of the second resection. In 16 (4 with recurrent, 12 with primary glioblastoma) cases, ioMRI revealed truly negative results without residual tumor and follow-up MRI confirmed complete resection. In 7 cases (3 with recurrent, 4 with primary glioblastoma) ioMRI revealed a suspicious result without tumorous tissue in the histopathological workup. In 2 (1 for each group) patients, residual tumorous tissue was detected in spite of negative ioMRI. IoMRI had a sensitivity of 95 % (94 % recurrent and 96 % for primary glioblastoma) and a specificity of 69.5 % (57 % and 75 %, respectively). The positive predictive value was 86 % (84 % for recurrent and 87 % for primary glioblastoma), and the negative predictive value was 88 % (80 % and 92 %, respectively). Conclusion ioMRI is effective for detecting remaining tumorous tissue after glioma resection. However, scars and leakage of contrast agent can be misleading and limit specificity. Key points · Intraoperative MRI (ioMRI) presents with a high sensitivity for residual contrast-enhancing tumorous tissue during glioma resection.. · Contrast leakage due to bleeding and scars with reactive contrast enhancement can cause possible misleading artifacts in ioMRI, leading to a limited specificity of ioMRI.. · Bleeding control in glioma resection is crucial for successful usage of ioMRO for glioma resection.. Citation Format · Heßelmann V, Mager A, Goetz C et al. Accuracy of High-Field Intraoperative MRI in the Detectability of Residual Tumor in Glioma Grade IV Resections. Fortschr Röntgenstr 2017; 189: 519 - 526.

Contributions of GABAergic and glutamatergic mechanisms to isoflurane-induced suppression of thalamic somatosensory information transfer.

Indications for a pivotal role of the thalamocortical network in producing the state of anesthesia have come from in vivo animal studies as well as imaging studies in humans. We studied possible synaptic mechanisms of anesthesia-induced suppression of touch perception in the rat's thalamus. Thalamocortical relay neurons (TCNs) receive ascending and descending glutamatergic excitatory inputs via NMDA and non-NMDA receptors (AMPAR) and are subjected to GABA(A)ergic inhibitory input which shapes the sensory information conveyed to the cortex. The involvement of these synaptic receptors in the suppressive effects of the prototypic volatile anesthetic isoflurane was assessed by local iontophoretic administration of receptor agonists/antagonists during extracellular recordings of TCNs of the ventral posteromedial nucleus responding to whisker vibration in rats anesthetized with isoflurane concentrations of approximately 0.9 vol.% (baseline) and approximately 1.9 vol.% (ISO high). ISO high induced a profound suppression of response activity reflected by a conversion of the sustained vibratory responses to ON responses. Administration of NMDA, AMPA, or GABA(A)R antagonists caused a reversal to sustained responses in 88, 94 and 88% of the neurons, respectively, with a recovery to baseline levels of response activity. The data show that the block of thalamocortical transfer of tactile information under ISO high may result from an enhancement of GABA(A)ergic inhibition and/or a reduction of glutamatergic excitation. Furthermore, they show that the ascending vibratory signals still reach the thalamic neurons under the high isoflurane concentration, indicating that this input is resistant to isoflurane while the attenuation of excitation may be brought about at the corticothalamic glutamatergic facilitatory input.

Increased responsiveness of cortical neurons in contrast to thalamic neurons during isoflurane-induced EEG bursts in rats.

The neuronal mechanisms underlying the electroencephalographic (EEG) burst-suppression pattern are not yet understood, however, they are generally attributed to interactions within thalamocortical networks. In contrast, we report that the sensory cortex and the thalamus are disconnected, with thalamic sensory processing being unaffected by cortical EEG bursts. We studied the activity of single neurons of the somatosensory thalamocortical system in rats during burst-suppression EEG induced by the volatile anesthetic, isoflurane. In neurons of the thalamic ventrobasal complex, the discharge rate in response to tactile stimulation of their receptive fields did not differ significantly during EEG bursts and isoelectric periods. In contrast, in neurons of the primary somatosensory cortex, the response magnitude was significantly greater during EEG bursts as compared with isoelectric periods (mean increase to 293%). The results suggest that the profound suppression of cortical sensory information processing by isoflurane is suspended during EEG burst-induced elevated cortical excitation.