Faculty Bibliography

Introduction: Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections leading to prolonged hospitalization and significant morbidity. Only a few prior studies have developed predictive risk models for CDI and all but one have utilized logistic regression (LR) models to identify risk factors. Automated machine learning (AutoML) programs consistently outperform standard LR models in non-medical contexts. This study aims to investigate the utility of AutoML methods in developing a model for post-operative CDI prediction.
Method(s): We used an AutoML system developed by Amazon, Autogluon v0.3.1, to evaluate the prediction accuracy of post-surgical CDI using the 2016-2018 ACS NSQIP database. A total of A total of 3,049,617 patients and 79 pre-operative features were included in the model. Post-operative CDI was defined as CDI within 30 days of surgery. Models were trained for 4 hours to optimize performance on the Brier score, with lower being better. Validation of all performance metrics was done using the 2019 NSQIP database.
Result(s): 0.36% of the patients (n = 11,001) developed post-operative CDI. Brier scores were calculated for each model with the top performing model being an ensembled neural net model having a Brier score of 0.0027 on the test set. The corresponding AUROC and AUC-PR was 0.840 and 0.015 respectively (Figure).
Conclusion(s): The models generated via AutoML to predict post-operative CDI had discriminatory characteristics greater than or equal to those models reported in the literature. Future post-operative CDI models may benefit from automated machine learning techniques

BACKGROUND Invasive mucormycosis is a rare, life-threatening infection that requires urgent medical management. Here we describe a patient who developed invasive mucormycosis after receiving only a short course of dexamethasone. The purpose is to highlight this atypical presentation of a rare disease. CASE REPORT A 74-year-old woman with a medical history of diabetes mellitus (DM), hypertension, hyperlipidemia, and small cell lung cancer with metastasis to the brain presented to the Emergency Department with altered mental status and a hyperosmolar hyperglycemic state. Three weeks before, she had been diagnosed with DM (hemoglobin A1c [HbA1c] 6.5%) and was started on dexamethasone to treat cerebral edema. On admission, her HbA1c was 10.8%, although she had received only a short course of dexamethasone. Her physical exam was concerning for left eyelid swelling and ophthalmoplegia. Computed tomography of the head and neck revealed signs of left ocular proptosis and invasive rhinomaxillary fungal disease. The patient underwent urgent surgical debridement; subsequent magnetic resonance imaging revealed extensive fungal disease extending into her left inferior frontal lobe. A surgical pathology report was positive for Rhizopus oryzae and Stenotrophomonas maltophilia. Her blood cultures were positive for methicillin-susceptible Staphylococcus aureus. She was treated with antibiotics and amphotericin B. Her clinical course was complicated by hypokalemia. She eventually recovered and was discharged from the hospital. CONCLUSIONS This case highlights an atypical presentation of mucormycosis. Clinicians should remain vigilant for this rare complication of dexamethasone use even when the therapy is given for a short time.

We present a 64-year-old woman who developed symptoms of acute pericarditis three days after undergoing intravesical instillation of mitomycin C following transurethral bladder tumor resection. Mitomycin C is a chemotherapeutic agent which acts by alkylation of DNA and is known to be cardiotoxic when systemically administered. Despite classic pericarditis symptoms, the patient underwent an urgent coronary angiogram due to elevated cardiac troponin I level, EKG changes, and wall motion abnormalities on her echocardiogram. During her angiogram, it was found that she had multiple stenotic coronary artery lesions, with no acute total coronary occlusions, and percutaneous coronary intervention (PCI) was done with placement of a single drug-eluting stent for a 95% stenotic lesion in the left anterior descending artery. The patient was discharged after an uneventful hospitalization on dual antiplatelet therapy with aspirin and prasugrel, and colchicine for pericarditis. It is likely that the patient's presentation was the result of a perimyocardial inflammatory process secondary to intravesically administered mitomycin C, rather than an acute coronary syndrome. While the pathophysiological basis of cardiotoxicity of systemically administered mitomycin C is well documented, more studies are needed to determine whether intravesical MMC may cause cardiotoxicity.

Idiopathic orbital inflammation is a common cause of acute orbital signs and symptoms. It is typically confined to the bony orbit; however, it can rarely involve contiguous structures with or without lytic change raising clinical suspicion for malignancy. Three cases of idiopathic inflammation of the orbit that affected adjacent structures are reported here; 2 cases had maxillary sinus involvement, while a third had extension in the temporal fossa.

BACKGROUND:The most prevalent long-term complications in patients undergoing laparoscopic adjustable gastric band (LAGB) surgery are symmetric pouch dilation and gastric prolapse (slippage). However, no published data or a reliable model are available to evaluate the actual mechanism of band slippage or how to prevent it. The objective of the present study was to construct an animal model of anterior gastric band prolapse and to use this model to evaluate the effectiveness of various arrangements of gastrogastric sutures and gastric wraps in preventing prolapse. METHODS:The esophagus of male mongrel dogs was accessed through the left chest, and a pressure transducer and an insufflation catheter were introduced. An AP-S Lap-Band (Allergan, Irvine, CA) filled to 10 cm(3) was placed using the pars flaccida technique. A standardized cut of meat was placed into the esophagus to simulate food impaction at a tight LAGB. After the placement of multiple different gastrogastric suture configurations, air was insufflated into the gastric pouch by way of the esophagus. RESULTS:Prolapse, identical to that seen in clinical practice, was reliably reproduced in this model by increased esophageal pressure acting on a LAGB outlet obstruction. In addition, prolapse was reproduced with all gastrogastric configurations that did not secure the anterior gastric wall to within 1.5 cm of the lesser curve. CONCLUSION/CONCLUSIONS:The results of the present study support the theory that prolapse is caused by esophageal peristalsis against an occlusion at the level of the LAGB. In this canine model, gastrogastric sutures encompassing the anterior gastric wall were integral to preventing prolapse.

The catalase-peroxidase (KatG) of Mycobacterium tuberculosis (Mtb) is important for the virulence of this pathogen and also is responsible for activation of isoniazid (INH), an antibiotic in use for over 50 years in the first line treatment against tuberculosis infection. Overexpressed Mtb KatG contains a heterogeneous population of heme species that present distinct spectroscopic properties and, as described here, functional properties. A six-coordinate (6-c) heme species that accumulates in the resting enzyme after purification is defined as a unique structure containing weakly associated water on the heme distal side. We present the unexpected finding that this form of the enzyme, generally present as a minority species along with five-coordinate (5-c) enzyme, is the favored reactant for ligand binding. The use of resting enzyme samples with different proportional composition of 5-c and 6-c forms, as well as the use of KatG mutants with replacements at residue 315 that have different tendencies to stabilize the 6-c form, allowed demonstration of more rapid cyanide binding and preferred peroxide binding to enzyme containing 6-c heme. Optical-stopped flow and equilibrium titrations of ferric KatG with potassium cyanide reveal complex behavior that depends in part on the amount of 6-c heme in the resting enzymes. Resonance Raman and low-temperature EPR spectroscopy clearly demonstrate favored ligand (cyanide or peroxide) binding to 6-c heme. The 5-c and 6-c enzyme forms are not in equilibrium on the time scale of the experiments. The results provide evidence for the likely participation of specific water molecule(s) in the first phases of the reaction mechanism of catalase-peroxidase enzymes.