Faculty Bibliography

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one's sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one's HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP.

Malaria is still one of leading infectious diseases in the world being a great global health burden. Pathological anemia is one of the most common malariaassociated complications, which accounts to both great morbidity and mortality of the infection. Our lab has recently identified autoantibodies that target the membrane lipid phosphatidylserine (PS) on uninfected erythrocytes as a major promoter of malarial anemia both in a rodent model and correlating with P. falciparum malarial anemia in patients. The aim of this work was to identify the population of B-cells that are responsible for the production of these autoantibodies as well as characterizing the mechanism by which they arise during malarial infection. Our results have identified an atypical population of B-cells expressing the transcription factor T-bet as being major producers of anti-PS antibodies during malarial anemia. Additionally we have identified parasite DNA along with inflammatory cytokine IFNgamma as essential signals that synergize to promote the development and appearance of these autoreactive T-bet⁺ B-cells. Similarly, the lack of any of these signals ameliorated severe anemia during a rodent malarial infection model. We have also identified both expansion of T-bet Bcells and production of anti-PS antibodies in ex-vivo cultures of naive human PBMCs exposed to P. falciprum infected erythrocyte lysates. Lastly, we have also observed the expansion of T-bet⁺ B-cells correlating with both anti-PS antibodies and anemia during rodent trypanosoma (T. brucei) infection. These results provide mechanistic insights about the appearance of autoimmunity during infection and attribute a role for autoimmunity in contributing to pathology during parasitic infections

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.

The prevalence of type 2 diabetes is rising worldwide, especially in older adults. Diet and lifestyle, particularly plant-based diets, are effective tools for type 2 diabetes prevention and management. Plant-based diets are eating patterns that emphasize legumes, whole grains, vegetables, fruits, nuts, and seeds and discourage most or all animal products. Cohort studies strongly support the role of plant-based diets, and food and nutrient components of plant-based diets, in reducing the risk of type 2 diabetes. Evidence from observational and interventional studies demonstrates the benefits of plant-based diets in treating type 2 diabetes and reducing key diabetes-related macrovascular and microvascular complications. Optimal macronutrient ratios for preventing and treating type 2 diabetes are controversial; the focus should instead be on eating patterns and actual foods. However, the evidence does suggest that the type and source of carbohydrate (unrefined versus refined), fats (monounsaturated and polyunsaturated versus saturated and trans), and protein (plant versus animal) play a major role in the prevention and management of type 2 diabetes. Multiple potential mechanisms underlie the benefits of a plant-based diet in ameliorating insulin resistance, including promotion of a healthy body weight, increases in fiber and phytonutrients, food-microbiome interactions, and decreases in saturated fat, advanced glycation endproducts, nitrosamines, and heme iron.

Limbic encephalitis presents as altered mood, memory loss and confusion. Clinical features may include psychiatric symptoms and seizures. In contrast to paraneoplastic disorders, non-paraneoplastic autoimmune encephalitis often responds to immunotherapy and sometimes with marked recovery. However, relapse can occur. An 82-year-old male presented with subacute episodes of memory loss over a few days. The patient was unable to recognize his own home and family members. Physical exam was unremarkable. Neuropsychological assessment revealed deficits in cognitive performance that could be consistent with moderate dementia or a more rapidly progressive encephalopathy. Agitated behavior and anxiety were also noted. Laboratory evaluation included hyponatremia, which was corrected with no symptom improvement. B12, TSH, and HIV were normal. CSF analysis revealed 10 WBCs/muL, Glucose-52 mg/dl, Protein-62 mg/dl and was negative for infectious, neoplastic causes, varicella, VDRL, viral cultures, NMDA receptor antibody, GAD 65 antibody and Anti-Hu antibody. Occult malignancy work up with CT scan of chest and abdomen and colonoscopy was normal. Serum for voltage-gated potassium channel antibodies was positive at 849 pmol/l (>88). EEG showed occasional focal left fronto-temporal slowing without epileptiform activity. MRI revealed focal enhancement of the medial left temporal lobe consistent with limbic encephalitis. The patient started high dose steroids with improvement in memory and complete resolution of focal abnormality within the left hippocampal/parahippocampal region suggestive of resolving encephalitis. At seven months after tapering steroids the patient presented with myoclonus and recurrent memory loss. MRI demonstrated recurrent encephalitis with gyral swelling and FLAIR hyperintensity in the left temporal lobe. The patient was restarted on high dose steroids with addition of Rituximab. This case illustrates that limbic encephalitis can present as a rapidly progressive dementia. Differential diagnosis should include more unusual forms of rapidly progressive dementia such as Jakob-Creutzfeldt disease if myoclonus is present, Lewy body dementia if waxing and waning memory, and Alzheimer's dementia with acute delirium if presenting over a period of months. In this patient, MRI changes were crucial to recognizing a potentially reversible limbic encephalitis. Early recognition and treatment may decrease relapse and reduce functional impairment

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.

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.

BACKGROUND: In 2012 The Joint Commission implemented new Tobacco Treatment (TOB) performance measures for hospitals. A study evaluated the impact of a hospital-based electronic health record (EHR) intervention on adherence to the revised TOB measures. METHODS: The study was conducted in two acute care hospitals in New York City. Data abstracted from the EHR were analyzed retrospectively from 4,871 smokers discharged between December 2012 and March 2015 to evaluate the impact of two interventions: an order set to prompt clinicians to prescribe pharmacotherapy and a nurse-delivered counseling module that automatically populated the nursing care plan for all smokers. The study estimated the relative odds of a patient being prescribed medication and/or receiving smoking cessation counseling in the intervention period compared to the baseline time period. RESULTS: There was a modest increase in medication orders (odds ratio [OR], 1.35). In contrast, rates of counseling increased 10-fold (OR, 10.54). Patients admitted through surgery were less likely to receive both counseling and medication compared with the medicine service. CONCLUSION: Hospitalization presents an important opportunity to engage smokers in treatment for primary and secondary prevention of tobacco-related illnesses. EHRs can be leveraged to facilitate integration of TOB measure requirements into routine inpatient care; however, the smaller effect on prescribing patterns suggests limitations in this approach alone in changing clinician behavior to meet this measure. The success of the nurse-focused EHR-driven intervention suggests an effective tool for integrating the cessation counseling component of the new measures and the importance of nursing's role in achieving the Joint Commission measure targets.

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.

PURPOSE/OBJECTIVE:The objective of the study was to compare the psychiatric and behavioral side effect (PBSE) profiles of both older and newer antiepileptic drugs (AEDs) in children and adolescent patients with epilepsy. METHOD/METHODS:We used logistic regression analysis to test the correlation between 83 non-AED/patient related potential predictor variables and the rate of PBSE. We then compared for each AED the rate of PBSEs and the rate of PBSEs that led to intolerability (IPBSE) while controlling for non-AED predictors of PBSEs. RESULTS:922 patients (≤18 years old) were included in our study. PBSEs and IPBSEs occurred in 13.8% and 11.2% of patients, respectively. Overall, a history of psychiatric condition, absence seizures, intractable epilepsy, and frontal lobe epilepsy were significantly associated with increased PBSE rates. Levetiracetam (LEV) had the greatest PBSE rate (16.2%). This was significantly higher compared to other AEDs. LEV was also significantly associated with a high rate of IPBSEs (13.4%) and dose-decrease rates due to IPBSE (6.7%). Zonisamide (ZNS) was associated with significantly higher cessation rate due to IPBSE (9.1%) compared to other AEDs. CONCLUSION/CONCLUSIONS:Patients with a history of psychiatric condition, absence seizures, intractable epilepsy, or frontal lobe epilepsy are more likely to develop PBSE. PBSEs appear to occur more frequently in adolescent and children patients taking LEV compared to other AEDs. LEV-attributed PBSEs are more likely to be associated with intolerability and subsequent decrease in dose. The rate of ZNS-attributed IPBSEs is more likely to be associated with complete cessation of AED.