Nonhepatic Hyperammonemia With Septic Shock: Case and Review of Literature.

Elevated ammonia levels lead to cerebral edema, encephalopathy, seizures, coma, and death. Hyperammonemia is primarily associated with liver disease; however, there are rare cases without liver disease. Noncirrhotic hyperammonemia is primarily due to increased production and/or decreased elimination of ammonia. We present a rare case of a 35-year-old female with severe acute noncirrhotic hyperammonemia associated with gram-negative septic shock and a suspected undiagnosed partial urea cycle enzyme deficiency. She had elevated blood and urine amino acid levels speculated to be due to an underlying urea cycle defect, which was unmasked in the setting of septic shock with urea splitting bacteria leading to severely elevated ammonia levels. Ammonia levels were rapidly corrected with hemodialysis, as other conventional treatments failed. We highlight the importance of considering noncirrhotic causes of hyperammonemia in patients with elevated ammonia levels and intact liver function. Prompt treatment should begin with reducing the catabolic state, nitrogen scavenging, replacing urea cycle substrates, decreasing intestinal absorption, and augmented removal of ammonia with renal replacement therapy.

Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation as the Initial Presentation of Anti-neutrophillic Cytoplasmic Auto-antibody Positive Vasculitis.

Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory state of lung injury that can require acute interventions including mechanical ventilation as well as emergent veno-venous extracorporeal membrane oxygenation (VV-ECMO) for management. Etiologies of ARDS are not clearly discernible in certain cases and can vary from sepsis, pneumonia, trauma and intoxication. Anti-nuclear cytoplasmic auto-antibody (ANCA)-associated vasculitis (AAV) is a group of several conditions that can have pulmonary complications including ARDS. We present a case where the primary manifestation of myeloperoxidase (MPO)-ANCA positive vasculitis was ARDS, in order to highlight the importance of investigating rare vasculitides as the underlying cause of ARDS and the importance of ECMO as an early life-saving intervention for the management of ARDS.

Utilizing the Promise of Omadacycline in a Resistant, Non-tubercular Mycobacterial Pulmonary Infection.

The non-tubercular mycobacterium, Mycobacterium abscessus (M. abscessus), is a resistant, opportunistic pathogen that causes lung infections that are not curable, but which can be controlled with appropriate antibiotic regimens. A new broad-spectrum tetracycline analog called omadacycline was approved in 2018 in the United States for the treatment of bacterial, community-acquired pneumonia and acute skin infections. We discuss a case to assess the effect of this novel antibiotic in the management of a nefariously resistant M. abscessus infection. Our patient had underlying chronic bronchiectasis and a long-standing M.abscessus infection, along with numerous drug allergies and previously failed antibiotic regimens. All of these factors entailed a disease process that was difficult to manage and a worsening morbidity. The utilization of omadacycline in this case addressed a multitude of problems by improving ease of administration and circumventing the patient's allergic reaction to antibiotics; on follow-up, the patient demonstrated an improved clinical status including well-controlled symptoms and weight gain.

Traumatic brain injury-induced ependymal ciliary loss decreases cerebral spinal fluid flow.

Traumatic brain injury (TBI) afflicts up to 2 million people annually in the United States and is the primary cause of death and disability in young adults and children. Previous TBI studies have focused predominantly on the morphological, biochemical, and functional alterations of gray matter structures, such as the hippocampus. However, little attention has been given to the brain ventricular system, despite the fact that altered ventricular function is known to occur in brain pathologies. In the present study, we investigated anatomical and functional alterations to mouse ventricular cilia that result from mild TBI. We demonstrate that TBI causes a dramatic decrease in cilia. Further, using a particle tracking technique, we demonstrate that cerebrospinal fluid flow is diminished, thus potentially negatively affecting waste and nutrient exchange. Interestingly, injury-induced ventricular system pathology resolves completely by 30 days after injury as ependymal cell ciliogenesis restores cilia density to uninjured levels in the affected lateral ventricle.

GABA and glutamate are not colocalized in mossy fiber terminals of developing rodent hippocampus.

It has been hypothesized that, in the developing rodent hippocampus, mossy fiber terminals release GABA together with glutamate. Here, we used transgenic glutamic acid decarboxylase-67 (GAD67)-GFP expressing mice and multi-label immunohistochemistry to address whether glutamatergic and GABAergic markers are colocalized. We demonstrate that in the dentate gyrus, interneurons positive for GABA/GAD are sparsely distributed along the edge of the hilus, in a different pattern from that of the densely packed granule cells. Co-staining for synaptophysin and vesicular glutamate transporter1 (VGLUT1) in postnatal day 14 brain sections from both mice and rats showed mossy fiber terminals as a group of large (2-5 µm in diameter) VGLUT1-positive excitatory presynaptic terminals in the stratum lucidum of area CA3a/b. Furthermore, co-staining for synaptophysin and vesicular GABA transporter (VGAT) revealed a group of small-sized (∼0.5 µm in diameter) inhibitory presynaptic terminals in the same area where identified mossy fiber terminals were present. The two types of terminals appeared to be mutually exclusive, and showed no colocalization. Thus, our results do not support the hypothesis that GABA is released as a neurotransmitter from mossy fiber terminals during development.

Dietary branched chain amino acids ameliorate injury-induced cognitive impairment.

Neurological dysfunction caused by traumatic brain injury results in profound changes in net synaptic efficacy, leading to impaired cognition. Because excitability is directly controlled by the balance of excitatory and inhibitory activity, underlying mechanisms causing these changes were investigated using lateral fluid percussion brain injury in mice. Although injury-induced shifts in net synaptic efficacy were not accompanied by changes in hippocampal glutamate and GABA levels, significant reductions were seen in the concentration of branched chain amino acids (BCAAs), which are key precursors to de novo glutamate synthesis. Dietary consumption of BCAAs restored hippocampal BCAA concentrations to normal, reversed injury-induced shifts in net synaptic efficacy, and led to reinstatement of cognitive performance after concussive brain injury. All brain-injured mice that consumed BCAAs demonstrated cognitive improvement with a simultaneous restoration in net synaptic efficacy. Posttraumatic changes in the expression of cytosolic branched chain aminotransferase, branched chain ketoacid dehydrogenase, glutamate dehydrogenase, and glutamic acid decarboxylase support a perturbation of BCAA and neurotransmitter metabolism. Ex vivo application of BCAAs to hippocampal slices from injured animals restored posttraumatic regional shifts in net synaptic efficacy as measured by field excitatory postsynaptic potentials. These results suggest that dietary BCAA intervention could promote cognitive improvement by restoring hippocampal function after a traumatic brain injury.