Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Muscle-specific kinase-antibodies (MuSK-ABs) are detected in ~ 6% of MG, but data on outcome of ...MuSK-MCs are still lacking. We made a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody positive MG (AchR-MG) or MuSK-MG between 2006 and 2015 in a retrospective German multicenter study. We identified 19 MuSK-AB associated MCs in 15 patients and 161 MCs in 144 patients with AchR-ABs only. In contrast to patients with AchR-AB, MuSK-AB patients were more often female (
p
= 0.05, OR = 2.74) and classified as Myasthenia Gravis Foundation of America-class IV before crisis (
p
= 0.04, OR = 3.25). MuSK-AB patients suffer more often from multiple chronic disease (
p
= 0.016, OR = 4.87) and were treated more invasively in terms of plasma exchanging therapies (not significant). The number of days of mechanical ventilation (MV) (43.0 ± 53.1 vs. 17.4 ± 18;
p
< 0.0001), days on an intensive care unit (ICU) (45.3 ± 49.5 vs. 21.2 ± 19.7;
p
< 0.0001), and hospital-length of stay (LOS) (55.9 ± 47.6 vs. 28.8 ± 20.9 days;
p
< 0.0001) were significantly increased in MuSK-MC. Remarkable is that these changes were mainly due to patients with MusK-ABs only, whereas patients’ outcome with both antibodies was similar to AchR-MCs. Furthermore, our data showed a shortened duration of MV after treatment with plasma exchanging therapies compared to treatment with intravenous immunoglobulin in MuSK-MCs. We conclude that MuSK-AB-status is associated with a longer need of MV, ICU-LOS, and hospital-LOS in MC, and therefore recommend early initiation of a disease-specific therapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
OBJECTIVETo determine demographic characteristics, clinical features, treatment regimens, and outcome of myasthenic crisis (MC) requiring mechanical ventilation (MV).
METHODSAnalysis of patients who ...presented with MC between 2006 and 2015 in a German multicenter retrospective study.
RESULTSWe identified 250 cases in 12 participating centers. Median age at crisis was 72 years. Median duration of MV was 12 days. Prolonged ventilation (>15 days) depended on age (p = 0.0001), late-onset myasthenia gravis (MG), a high Myasthenia Gravis Foundation of America Class before crisis (p = 0.0001 for IVb, odds ratio OR = infinite), number of comorbidities (>3 comorbiditiesp = 0.002, OR 2.99), pneumonia (p = 0.0001, OR 3.13), and resuscitation (p = 0.0008, OR 9.15). MV at discharge from hospital was necessary in 20.5% of survivors. Patients with early-onset MG (p = 0.0001, OR 0.21), thymus hyperplasia (p = 0.002, OR 0), and successful noninvasive ventilation trial were more likely to be ventilated for less than 15 days. Noninvasive ventilation in 92 cases was sufficient in 38%, which was accompanied by a significantly shorter duration of ventilation (p = 0.001) and intensive care unit (ICU) stay (p = 0.01). IV immunoglobulins, plasma exchange, and immunoadsorption were more likely to be combined sequentially if the duration of MV and the stay in an ICU extended (p = 0.0503, OR 2.05). Patients who received plasma exchange or immunoadsorption as first-line therapy needed invasive ventilation significantly less often (p = 0.003). In-hospital mortality was 12%, which was significantly associated with the number of comorbidities (>3) and complications such as acute respiratory distress syndrome and resuscitation. Main cause of death was multiorgan failure, mostly due to sepsis.
CONCLUSIONMortality and duration of MC remained comparable to previous reports despite higher age and a high disease burden in our study. Prevention and treatment of complications and specialized neurointensive care are the cornerstones in order to improve outcome.
Background A noninvasive model of necrohemorrhagic pancreatitis induced by simultaneous intravenous cerulein/enterokinase (EK) infusion has recently been established in rats. The aim of the present ...study was to establish this new model in mice and to compare it with the rat model. Methods Male Balb/C mice (20 to 25 g) were used for the experiments. Pancreatitis was induced by simultaneous intravenous infusion of cerulein and EK. Controls were infused with either 0.9% NaCl, cerulein, or EK. Animals were humanely killed 6 hours after start of infusions. Pancreatic and pulmonary injury was assessed by histology, wet-to-dry weight ratio, and myeloperoxidase activity. Systemic cytokine, amylase, and lactate dehydrogenase (LDH) levels in blood were measured to assess pancreatic and systemic inflammatory response. To evaluate the role of protease activity in this model, trypsin, cathepsin B, and elastase activity were measured in pancreatic tissue. Survival experiments were performed to determine survival time and tissue injury in the later course of the disease. Results Mice with simultaneous cerulein/EK infusion developed marked local and systemic organ injury compared with those animals who received cerulein or EK alone. Pancreatic and pulmonary injury increased with high concentrations of cerulein/EK infusions. Survival decreased in these animals. Whereas acinar cell apoptosis was an early finding, pancreatic necrosis was observed later in the course of the disease. Serum levels of LDH, interleukin (IL)-1α, and IL-1β reflected cell damage and the systemic inflammatory response. Protease activity in pancreatic tissue was greatest in animals with simultaneous cerulein/EK infusion. Conclusions Using intravenous cerulein/EK infusions, a model of lethal acute pancreatitis has been established in mice. Major pancreatic edema, acinar cell apoptosis and necrosis, and pulmonary leukocyte sequestration are characteristic findings in this model. Although pancreatic injury was not as strong as in the rat model, this model may prove useful for future studies in transgenic mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
IMPORTANCE: Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH). OBJECTIVE: To assess the ...association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption. EXPOSURES: Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment. MAIN OUTCOMES AND MEASURES: Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome. RESULTS: Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 19.8%) vs INR of ≥1.3 (264/636 41.5%; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 33.1%) vs ≥160 mm Hg (98/187 52.4%; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 18.1% vs 220/498 44.2% not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 13.5% vs 103/498 20.7%; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 5.2% vs no OAC: 82/547 15.0%; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 8.1% vs no OAC: 36/547 6.6%; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%). CONCLUSIONS AND RELEVANCE: Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01829581
Background:
Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk ...factors correlating with a tracheostomy, as well as the impact of an early tracheostomy on ventilation time and ICU length of stay (LOS) in MC.
Methods:
Retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015 to assess demographic/diagnostic data, rates and timing of tracheostomy and outcome.
Results:
In 107 out of 215 MC (49.8%), a tracheostomy was performed. Patients without tracheostomy were more likely to have an early-onset myasthenia gravis (27 25.2% vs 12 11.5%, p = 0.01). Patients receiving a tracheostomy, however, were more frequently suffering from multiple comorbidities (20 18.7% vs 9 8.3%, p = 0.03) and also the ventilation time (34.4 days ± 27.7 versus 7.9 ± 7.8, p < 0.0001) and ICU-LOS (34.8 days ± 25.5 versus 12.1 ± 8.0, p < 0.0001) was significantly longer than in non-tracheostomized patients. Demographics and characteristics of the course of the disease up to the crisis were not significantly different between patients with an early (within 10 days) compared to a late tracheostomy. However, an early tracheostomy correlated with a shorter duration of MV at ICU (26.2 days ± 18.1 versus 42.0 ± 33.1, p = 0.006), and ICU-LOS (26.2 days ± 14.6 versus 42.3 ± 33.0, p = 0.003).
Conclusion:
Half of the ventilated patients with MC required a tracheostomy. Poorer health condition before the crisis and late-onset MG were associated with a tracheostomy. An early tracheostomy (≤ day 10), however, was associated with a shorter duration of MV and ICU-LOS by 2 weeks.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abstract only Background: The Stroke East Saxony Network (SOS-NET) provides tele-consultations for acute stroke patients presenting to local hospitals in eastern Saxony, Germany. Experienced stroke ...neurologists perform tele-consultations 24/7. They take a clinical history, perform a video examination and a standardized evaluation of acute cerebral CT including Alberta Stroke Program Early CT Score (ASPECTS) before suggesting further management. We assessed the diagnostic accuracy and clinical impact of CT evaluation by stroke neurologists in this acute tele-stroke-service. Methods: To assess the diagnostic accuracy of stroke neurologists in CT-interpretation, two experienced neuroradiologists re-evaluated all CT scans of tele-consultations in 2009 blinded to clinical findings. We defined discrepant findings as deviations in the ASPECTS >1 or if differential diagnoses like tumor or intracranial hemorrhage (ICH) were not detected by the stroke neurologists. To assess the clinical impact, all discrepant results were subsequently discussed and re-evaluated of all involved neurologists and neuroradiologists regarding its possible influence on therapeutic decisions and on patients’ outcome. Results: In 2009, we performed 583 tele-consultations (353 ischemic strokes, 119 primary ICH and 111 stroke mimics). In 102 patients with ischemic stroke (29%) thrombolysis was performed with eight bleeding complications (7.8%). The neuroradiologists detected discrepant findings in 44 CT scans (7.5%), however corrected, their image interpretation if unblinded to the clinical information in four patients. We regarded the diagnostic inaccuracy by neurologist as clinically relevant in nine patients (1.5%). In one patient, the stroke neurologist missed a small chronic subdural hematoma. The patient did not receive thrombolysis because of mild clinical findings. Consequently, the false diagnosis did not affect treatment and clinical outcome in this patient. Furthermore, stroke neurologists missed extensive early ischemic changes in the middle cerebral artery territory in eight patients and recommended thrombolytic therapy. We observed symptomatic ICH in five of these patients (62.5%; 0.9% of the total cohort). Conclusion: Trained stroke neurologists had a high diagnostic accuracy in CT interpretation in acute tele-stroke-service, compared to experienced neuroradiologists. Clinically relevant misinterpretations of the CT scans were rare (1.5%). However, regarding the potential risk of thrombolytics, stroke neurologists should continuously be trained in interpreting CT scans of acute stroke patients.
The study attempts to evaluate the relationship, if any, between anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulant-related intracerebral ...hemorrhage. The results indicate that a strong association was observed between them.
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