Faculty Bibliography

Plerixafor (P), an agent that selectively and reversibly binds to the chemokine receptor CXCR4, has been approved in combination with G-CSF (P + G-CSF) for stem cell (SC) mobilization in patients with multiple myeloma (MM). The goal of this study was to determine the SC collection success rate of P + G-CSF using a clinically relevant outcome defined as the ability to collect at least 5 × 10⁶CD34⁺cells/kg to allow safely two transplants, and identify risk factors impacting SC mobilization. One hundred and thirty-eight patients were mobilized with P + G-CSF upfront following induction. The SC collection success rate was 92.8%. We identified exposure to lenalidomide alone (p = .038), WBC count <4 × 10³/mcL prior to mobilization (p = .01) and non-African American race (p = .019), as risk factors for low efficiency by multivariate analysis. This study demonstrates that P + G-CSF is highly efficient in MM patients and provides strong support for its upfront use in SC collection for MM patients.

Thiazolyl peptides are a class of natural products with potent Gram-positive antibacterial activities. Lack of aqueous solubility precluded this class of compounds from advancing to clinical evaluations. Nocathiacins and thiazomycins are sub-classes of thiazolyl peptides that are endowed with structural features amenable for chemical modifications. Semi-synthetic modifications of nocathiacin led to a series of analogs with improved water solubility, while retaining potency and antibacterial spectrum. We studied the activities of a selection of two natural products (nocathiacin and thiazomycin) as well as seven polar semi-synthetic analogs against twenty clinical strains of Mycobacterium tuberculosis with MDR phenotypes. Two compounds show useful activity against H37Rv strain with MIC values ⩽1 μM, two (⩽0.5 μm) and three (⩽10 μm). These two derivatives showed MIC values ⩽2.5 μm against most of the 20 MDR strains regardless their resistance profile. Specifically, these lack cross-resistance to rifampicin, isoniazid and moxifloxacin.

Ceftazidime-avibactam resistance is mediated by bla_KPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different bla_KPC-3 mutations (n = 5) or wild-type bla_KPC-3 (n = 2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3, bla_KPC-3 mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistant K. pneumoniae infections may select for carbapenem resistance.

Infections caused by foodborne enteric pathogens including typhoidal and non-typhoidal Salmonella species can mimic symptoms of acute appendicitis. The association between such bacterial pathogens and pathology-proven acute appendicitis has been described, but this link is poorly understood. Here we describe a case of a young man with typhoid fever presenting with histology-proven acute appendicitis requiring urgent appendectomy, and provide a brief review of relevant literature to prompt more widespread recognition of this rare cause of a common surgical emergency.

BACKGROUND: Testing for venous thromboembolism (VTE) is associated with cost and risk to patients (e.g. radiation). To assess the appropriateness of imaging utilization at the provider level, it is important to know that provider's diagnostic yield (percentage of tests positive for the diagnostic entity of interest). However, determining diagnostic yield typically requires either time-consuming, manual review of radiology reports or the use of complex and/or proprietary natural language processing software. OBJECTIVES: The objectives of this study were twofold: 1) to develop and implement a simple, user-configurable, and open-source natural language processing tool to classify radiology reports with high accuracy and 2) to use the results of the tool to design a provider-specific VTE imaging dashboard, consisting of both utilization rate and diagnostic yield. METHODS: Two physicians reviewed a training set of 400 lower extremity ultrasound (UTZ) and computed tomography pulmonary angiogram (CTPA) reports to understand the language used in VTE-positive and VTE-negative reports. The insights from this review informed the arguments to the five modifiable parameters of the NLP tool. A validation set of 2,000 studies was then independently classified by the reviewers and by the tool; the classifications were compared and the performance of the tool was calculated. RESULTS: The tool was highly accurate in classifying the presence and absence of VTE for both the UTZ (sensitivity 95.7%; 95% CI 91.5-99.8, specificity 100%; 95% CI 100-100) and CTPA reports (sensitivity 97.1%; 95% CI 94.3-99.9, specificity 98.6%; 95% CI 97.8-99.4). The diagnostic yield was then calculated at the individual provider level and the imaging dashboard was created. CONCLUSIONS: We have created a novel NLP tool designed for users without a background in computer programming, which has been used to classify venous thromboembolism reports with a high degree of accuracy. The tool is open-source and available for download at http://iturrate.com/simpleNLP. Results obtained using this tool can be applied to enhance quality by presenting information about utilization and yield to providers via an imaging dashboard.

Background and Study Aims: Fluorescent in-situ hybridization (FISH) performed on brush specimens is one of the most accurate and widely used second line diagnostic modalities. Our goal was to compare the diagnostic accuracy of FISH in the detection of malignancy compared with other standard diagnostic modalities, including brush cytology and biopsy specimens over a ten year period of prospective data collection. Patients and methods: We conducted a review of a prospectively maintained database of biliary strictures between 2006 and 2016. Patients with a final pathologic diagnosis or a conclusive follow-up were included. Cytology and biopsy results were considered positive for malignancy when suspicious or malignant cells were identified. We evaluated the performance of FISH polysomy (CEP 3, 7, and 17) and 9p21 deletion. Statistical analysis was performed with the Chi square and Fisher exact tests. Results: Of 382 who underwent evaluation for biliary strictures, 277 met inclusion criteria. 119 patients (42.8%) were found to have malignancy (58.0% pancreatic cancer, 37.0% cholangiocarcinoma, 5.0% other malignancies). Benign etiology included inflammatory strictures (63.9%), PSC (19.6%), post-operative (6.3%) or other benign etiologies (10.2%). The sensitivities for FISH and cytology were found to be 55.4% and 39.0%. Both cytology and FISH showed a very high specificity of 99.4%. The accuracy and AUC of FISH polysomy and cytology (AUC=.789) was significantly higher than cytology alone (AUC=.688; p<0.05). The addition of detection of 9p21 deletion led to no additional false positives but an additional diagnosis of 11/119 (9.2%) malignant cases, however there was a nonsignificant difference in the accuracy and AUC of FISH polysomy versus FISH polysomy plus 9p21 deletion. The combination of brush cytology, FISH polysomy and 9p21 deletion and any additional sampling (i.e. biopsy) taken during ERCP showed a sensitivity of 70.0% that was not significantly higher than cytology plus FISH polysomy. There were 36 (30.3 %) patients who had malignancies that were undetected by any of the diagnostic modalities studied. Conclusion: This is the largest prospective cohort of patients with biliary strictures evaluated by FISH. The very high specificity of FISH polysomy and 9p21 deletion suggests that a positive result is sufficient for the diagnosis of biliary malignancy. A limitation of our data is the relatively small number of PSC patients where specificity may be lower. The significantly higher sensitivity of both FISH polysomy and polysomy or 9p21 deletion compared to cytology and the non-significant improvement in sensitivity when combing further sampling methods supports the use of FISH as first line in the evaluation of cytology negative strictures. (Table Presented)

Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate (¹⁷⁷Lu-DOTATATE) is a treatment with good results in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEPNETs). However, there are some pitfalls that should be taken into consideration when evaluating the treatment response after PRRT. 354 Dutch patients with GEPNETs who were treated with ¹⁷⁷Lu-DOTATATE between March 2000 and December 2011 were retrospectively selected. Liver function parameters and chromogranin A were measured before each therapy and in follow-up. Anatomical imaging was performed before therapy and in follow-up. An increase in aminotransferases by ≥20% compared to baseline was observed in 83 of 351 patients (24%). In patients with an objective response (OR) and stable disease (SD) this increase was observed in 71/297 (24%) and in patients with progressive disease (PD) it was observed in 12/54 patients (22%). An increase in chromogranin A by ≥20% compared to baseline was observed in 76 patients (29%). This was present in 34% of patients who eventually had PD and 27% of patients who had OR/SD. In 70% of patients this tumour marker returned to baseline levels after therapy. An increase in liver enzymes and chromogranin A is not uncommon after PRRT. In the vast majority of patients this will resolve in follow-up. Clinicians should be aware that these changes may occur due to radiation-induced inflammation or disease progression and that repeated measurements over time are necessary to differentiate between the two.

The subtle signs and symptoms of substance use disorder (SUD) often go unrecognized by physicians in training. Many times, this is because primary care physicians are not trained to recognize SUDs as free-standing medical illnesses that can be successfully treated, and require primary care interventions. Physicians-in-training at the residency level may not know what these disorders looks like in their early and active phases, nor in phases of recovery. Most young physicians have never had the opportunity to speak with patients who are actively working to recover or in long-term recovery. In 2008, a major NYC teaching hospital (Lenox Hill Hospital) began to require all first-year primary care internal medical residents to attend a 12-hour Physician Alcohol and Addiction Training Program (PAAT). This innovative program utilizes patients as teachers. Each physician is paired with an alcoholic or addicted patient in recovery and actively involved in AA. In a powerful reversal of the traditional doctor-patient relationship, the patients, or "buddies" act as 1:1 teachers and mentors for the resident physicians, providing a profound and personal window into the experience of alcoholism and addiction, and modeling positive treatment outcomes and recovery. This work with buddies is integrated, in real time, with the training provided by physician faculty. Buddies accompany their resident physicians to an AA meeting and provide them with an understanding of 12-step sober support meetings as a powerful treatment modality. Each Buddy-Resident pair processes their AA experience, dispelling common myths about sober support meetings and dire prognosis of alcoholism and addiction. Residents get to know their buddies as people with expertise to offer them, and not simply as patients. They administer several screening tools (MAST, CAGE, and AUDIT) to their buddies, who are asked to answer both as they would have when actively using, and as they would now, looking backward from their current perches in recovery. This provides residents insight into the defensiveness, minimization and denial that they will face when screening for SUDs, and the critical need for cultivating longitudinal primary care relationships. Residents then take full biopsychosocial histories, and are encouraged to follow their curiosity and ask the questions that they would never ask if their buddies were their patients. The program concludes with resident presentations of their buddies' histories of use and recovery, getting feedback from both faculty and peers. Data about resident ratings of the program, utilizing the Wilcoxon matched-pairs signed-ranks pre-and post-tests, will be presented, as well as results demonstrating robust changes in students' perceptions after buddy mentoring, with the emergence of an understanding that substance use is a chronic relapsing medical disease that can be successfully treated, rather than an irreparable deficiency in moral character

BACKGROUND Electrocardiographic presentations of left ventricle aneurysms are diverse; however, a persistent ST segment elevation post myocardial infarction is most commonly reported. CASE REPORT The authors present a case of a 67-year-old man who presented to the emergency department after three days of chest pain and was found to have an acute myocardial infarction with an incidental finding of a left ventricular aneurysm. His surface electrocardiogram, however, demonstrated only inverted T waves in the precordial leads. He had a very elevated serum troponin I consistent with an acute myocardial injury which prompted a cardiac catheterization with angioplasty. Post angioplasty, he had persistent T wave inversions in the precordial leads. CONCLUSIONS It is important for clinicians to appreciate that the presence of newly inverted T waves in patients with a late presentation post myocardial infarction should raise a concern for a possible left ventricular aneurysm.