Corticosteroids in Generalized Autoimmune Myasthenia Gravis: A Narrative Review

No abstract is required for a review article as per instruction

Exercise Training for autoimmune myasthenia gravis: A review of safety and effectiveness based on existing literature

No abstract is required for a review article as per instruction

Delirium in the ICU: time to probe the hard questions

Prevalent in critically ill patients, delirium remains poorly understood and difficult to treat. In a cross-sectional study conducted in 12 countries, delirium was identified in close to one third of patients and was independently associated with increased mortality. While such epidemiological accounts represent an important cornerstone for research, scientific efforts are needed to elucidate the causes of delirium and the mechanisms underlying its association with poor outcomes

Septic-associated encephalopathy - everything starts at a microlevel

Sepsis-associated encephalopathy is associated with increased mortality and morbidity. Its pathophysiology remains insufficiently elucidated, although there is evidence for a neuroinflammatory process sequentially involving endothelial activation, blood-brain barrier alteration and cellular dysfunction and alteration in neurotransmission. Experimental studies have shown that microcirculatory dysfunction, a consequence of endothelial activation, is an early pathogenic step. To date, we do not know whether it is present in septic patients, whether it accounts for clinical features and whether it is treatable

Science review: The brain in sepsis – culprit and victim

On one side, brain dysfunction is a poorly explored complication of sepsis. On the other side, brain dysfunction may actively contribute to the pathogenesis of sepsis. The current review aimed at summarizing the current knowledge about the reciprocal interaction between the immune and central nervous systems during sepsis. The immune-brain cross talk takes part in circumventricular organs that, being free from blood-brain-barrier, interface between brain and bloodstream, in autonomic nuclei including the vagus nerve, and finally through the damaged endothelium. Recent observations have confirmed that sepsis is associated with excessive brain inflammation and neuronal apoptosis which clinical relevance remains to be explored. In parallel, damage within autonomic nervous and neuroendocrine systems may contribute to sepsis induced organ dysfunction

Učinak nalbufina ili ketamina na sposobnost ksilazina da održi sedaciju konja u stojećem stavu

Despite the pivotal role of α2-agonists for standing sedation in horses, these drugs possess several dose-dependent side effects. Therefore, this study aimed to determine the effect of nalbuphine or ketamine on xylazine requirements necessary to provide constantly moderate sedation in horses. Five healthy adult horses were subjected to three randomized treatments at one-week intervals as follows: xylazine (XYL) (xylazine: 0.55 mg/kg, IV; saline: bolus & CRI); xylazine/nalbuphine (XYL/NAL) (xylazine: 0.55 mg/kg, IV; nalbuphine: 0.3 mg/kg, IV & 0.23 mg/kg/hour CRI) and xylazine/ketamine (XYL/KET) (xylazine: 0.55 mg/kg, IV; ketamine: 0.1 mg/kg, IV & 0.5 mg/kg/hour CRI). On all occasions, moderate sedation was maintained for 120 minutes by administering additional xylazine boluses (0.14 mg/kg, IV) whenever lower sedation was demonstrated. All treatments were assessed in terms of the degree of sedation, the time of administering the first additional xylazine bolus, and xylazine requirements (presented as mg/kg/hour) for maintaining moderate sedation for 120 minutes. The degree of ataxia and adverse events were also monitored. Sedation scores were significantly higher than the baseline for all treatments over 120 minutes. A longer time before the first additional xylazine bolus and lower xylazine requirements (lower calculated infusion rates) for maintaining moderate sedation were evident following the XYL/NAL and XYL/KET treatments compared to the XYL treatment. All treatments were associated with an acceptable degree of ataxia and limited behavioral effects. In conclusion, both nalbuphine and ketamine were efficient in reducing xylazine requirements for constant sedation in horses. Further study is required for comprehensive testing of all studied combinations to elucidate the potential advantages of the demonstrated xylazine sparing effect.Unatoč ključnoj ulozi α2-agonista u sedaciji konja u stojećem stavu, ovi lijekovi imaju nekoliko nuspojava koje ovise o njihovoj dozi. Cilj je istraživanja bio odrediti učinak nalbufina ili ketamina na sposobnost ksilazina da održi umjerenu sedaciju u konja. Pet zdravih odraslih konja podvrgnuto je trima randomiziranim pokusima u intervalima od tjedan dana prema sljedećem protokolu: ksilazin (XYL; ksilazin 0,55 mg/kg, iv., fiziološka otopina bolus i CRI); ksilazin/nalbufin (XYL/NAL ksilazin 0,55 mg/kg, iv., nalbufin 0.3 mg/kg, iv. i 0,23 mg/kg/h CRI) i ksilazin/ketamin (XYL/KET; ksilazin 0,55 mg/kg, iv., ketamin 0.1 mg/kg, iv. i 0,5 mg/kg/h CRI). U sve je tri skupine održana umjerena sedacija tijekom 120 minuta. Kad god se pokazala niža sedacija, dodavan je bolus ksilazina (0,14 mg/kg, iv.). Procjenjivan je stupanj sedacije, vrijeme primjene prvog dodatnog bolusa ksilazina i potrebe za ksilazinom (prikazane u mg/kg/h) kako bi se održala umjerena sedacija tijekom 120 minuta. Praćeni su i stupanj ataksije odnosno štetnih događaja. Pokazatelji sedacije bili su znakovito veći u sva tri pokusa tijekom 120 minuta. Dulje vrijeme prije prvog dodatnog bolusa ksilazina i manje potrebe za ksilazinom (niža stopa infuzije) kako bi se održala umjerena sedacija uočeni su nakon primjene XYL/NAL i XYL/KET lijekova u usporedbi sa skupinom koja je primila samo XYL. U sve je tri skupine zapažen prihvatljiv stupanj ataksije i ograničeni učinci na ponašanje. Zaključeno je da su i nalbufin i ketamin učinkoviti u smanjenju potreba za ksilazinom kako bi se održala sedacija u konja. Potrebna su daljnja istraživanja i sveobuhvatno testiranje ovih kombinacija kako bi se ustanovile potencijalne prednosti smanjene primjene ksilazina uočene u ovom istraživanju

Weakness in the ICU: a call to action

Muscle weakness is prevalent in critically ill patients and can have a dramatic effect on short- and long-term outcomes, yet there are currently no interventions with proven efficacy in preventing or treating this complication. In a new randomized trial, researchers found that serial electrical muscle stimulation significantly mitigated ultrasound-defined muscle atrophy, and the treatment was not linked to adverse effects. Although preliminary, these results, together with other recent studies, indicate a paradigm shift to a proactive approach in managing neuromuscular complications in the ICU

Understanding brain dysfunction in sepsis

Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors

Brainstem dysfunction in critically ill patients

The brainstem conveys sensory and motor inputs between the spinal cord and the brain, and contains nuclei of the cranial nerves. It controls the sleep-wake cycle and vital functions via the ascending reticular activating system and the autonomic nuclei, respectively. Brainstem dysfunction may lead to sensory and motor deficits, cranial nerve palsies, impairment of consciousness, dysautonomia, and respiratory failure. The brainstem is prone to various primary and secondary insults, resulting in acute or chronic dysfunction. Of particular importance for characterizing brainstem dysfunction and identifying the underlying etiology are a detailed clinical examination, MRI, neurophysiologic tests such as brainstem auditory evoked potentials, and an analysis of the cerebrospinal fluid. Detection of brainstem dysfunction is challenging but of utmost importance in comatose and deeply sedated patients both to guide therapy and to support outcome prediction. In the present review, we summarize the neuroanatomy, clinical syndromes, and diagnostic techniques of critical illness-associated brainstem dysfunction for the critical care setting