Faculty Bibliography

A diagnosis of acute pancreatitis requires two of three diagnostic criteria to be present: elevated serum lipase, characteristic epigastric abdominal pain radiating to the back and/or abdominal tenderness, or CT evidence of pancreatitis. Here we describe a case of necrotizing pancreatitis in a patient with only mild abdominal pain and a normal serum lipase. A 55 year-old male presented with abdominal pain and subjective fevers for 5 days. 6 weeks prior, the patient was diagnosed with non-small cell lung cancer and CT scans for staging purposes showed no evidence of abdominal pathology. He had yet to undergo treatment for his malignancy. The patient then presented to the hospital two weeks prior to his current presentation with acute abdominal pain and inability to tolerate po. Labs revealed a normal lipase but CT abdomen and pelvis revealed acute pancreatitis. The patient was treated supportively and was subsequently discharged home. He felt well for the next 5 days but then presented to an outside hospital with subjective fevers and chills. He was treated with IV antibiotics for pneumonia but left against medical advice after 4 days and presented to our ER that evening with abdominal pain, nausea/vomiting. Physical exam revealed an afebrile man, non-toxic, with a soft abdomen and normoactive bowel sounds. He was mildly tender in all four abdominal quadrants. Labs revealed a serum glucose of 344. Urine toxicology was positive for cocaine. Serum lipase and amylase were 12.3 and 36, respectively. Urinalysis revealed 3+ ketones. CXR was stable with the patient's prior. The patient was initially treated with fluids and insulin for possible diabetic ketoacidosis, but by morning his condition worsened with development of a distended abdomen and guarding. Urgent CT revealed necrotizing pancreatitis with possible abscesses in the pancreatic head and tail. The patient was taken for laparoscopic debridement, which confirmed the diagnosis. The pancreatitis was thought to be due to alcohol-use. He eventually stabilized, and was discharged to rehab. Literature on acute pancreatitis with normal serum lipase is limited. Anecdotally, lipase-negative pancreatitis is thought to be mechanistically related to a "burnt-out pancreas" that is unable to synthesize the enzyme. However, our patient had a normal CT abdomen 6 weeks prior. We highlight this case for its challenging and unusual presentation of a common diagnosis

Therapeutic hypothermia favorably impacts neurologic outcomes in patients after cardiopulmonary arrest, although the appropriate target temperature is less clear. Its safety profile in patients with systemic sclerosis (SSc) and Raynaud phenomenon (RP), who may be at increased risk for ischemic complications, has not been addressed in the literature, to our knowledge. Digital lesions are commonly seen in patients with SSc, and cold-induced myocardial ischemia has also been reported. We describe a case of a man with SSc, RP, and digital ulcers who underwent therapeutic hypothermia after cardiopulmonary arrest. He regained full neurologic function, and except for digital necrosis, no hypothermia-associated adverse events were observed. Other risk factors for ischemia, such as cocaine use, may have contributed to the development of the digital necrosis. However, clinicians should be aware of the risk for ischemic complications in patients with SSc and RP when considering the appropriate target temperature after cardiopulmonary arrest.

Cell-based delivery of cell penetrating peptides (CPPs) could represent a new platform for intracellular peptide delivery to local tissues. Expressed CPPs, coupled to a secretory signal peptide (SP), can support intercellular transport. However, low secretion efficiency, which may correlate with the positive charge of most CPPs, has emerged as one of the main impediments for efficient intercellular transport. We have reported that a modified Tat-based CPP (Tatm) with reduced positive charge is secreted efficiently, but its transduction activity was greatly reduced. We now show that a triple repeat of Tatm (Tatm3x) with an elongated alpha-helical amphipathic structure enhances transduction activity and simultaneously retains its secretion efficacy, although passage through the secretory pathway reduces its cell-penetrating activity. SP-Tatm3x supports intercellular transport of fused fluorescent proteins, as well as cell entry and function of a pro-apoptotic peptide. In addition, SP-Tatm3x largely escapes RNA inhibition, which is identified as another potential impediment to CPP-mediated intercellular transport. Expression of SP-Tatm3x in heparan sulfate proteoglycan-negative cells further improves its transduction activity. These results demonstrate the feasibility of intercellular transport of proteins, but further work is needed to better understand the reduction of cell-penetrating activity associated with secretion of CPP-fusion proteins.