Faculty Bibliography

BACKGROUND:Pre-exposure prophylaxis (PrEP) for HIV involves using antiretroviral drugs to prevent individuals at high risk from acquiring HIV infection. Most practicing primary care providers believe PrEP to be safe and effective, but less than half have prescribed or referred for PrEP. Attitudes and prescribing patterns among house officers have not been well described previously. STUDY QUESTION/OBJECTIVE:Can an educational intervention enhance HIV PrEP practices among internal medicine house officers? STUDY DESIGN/METHODS:This study relied on a pretest/posttest design. All categorical trainees at a medium-sized internal medicine program were offered a baseline survey to assess their knowledge on PrEP. This was followed by a PrEP-focused educational intervention and a postintervention survey. MEASURES AND OUTCOMES/METHODS:Likert scales captured perceptions regarding safety, effectiveness, barriers, factors that would promote PrEP use, potential side effects, impact on risk-taking behavior, and provider comfort level in assessing behavioral risks and in PrEP prescribing. Data were analyzed using descriptive statistics, Wilcoxon signed rank test, and the Kruskal-Wallis test. Significance was accepted for P < 0.05. RESULTS:Forty-eight (100%) trainees participated in the educational session, 45 (94%) in a preintervention survey, and 36 (75%) in a postintervention survey. Before PrEP training, 22% of respondents were unaware of PrEP, 78% believed PrEP was effective, 66% believed PrEP was safe, 62% had fair or poor awareness of side effects; 18% of residents had referred for or prescribed PrEP, and 31% believed they were likely to prescribe PrEP in the next 6 months. After the intervention, 94% of trainees believed PrEP was effective (P < 0.001), 92% believed PrEP was safe (P < 0.001), and two-thirds believed they were likely to prescribe PrEP in the next 6 months. CONCLUSIONS:Brief, focused training on HIV prevention promotes awareness, acceptance, and likelihood of prescribing PrEP by internal medicine trainees.

Urothelial carcinoma (UC) is a common and frequently lethal cancer. Despite the presence of genomic alterations creating dependency on particular signaling pathways, the use of targeted therapies in advanced and metastatic UC has been limited. We performed an integrated analysis of whole-exome and RNA sequencing of primary and metastatic tumors in a patient with platinum-resistant UC. We found a strikingly high ERBB2 mRNA expression and enrichment of downstream oncogenic ERBB2 signaling in this patient's tumors compared with tumors from an unselected group of patients with UC (N=17). This patient had an exceptional sustained response to trastuzumab. Our findings show that oncogenic addiction to ERBB2 signaling potentially predicts response to ERBB2-directed therapy of UC.

Extramedullary hematopoiesis, which represents ectopic blood cell production, is usually an incidental finding accompanying hematologic pathology. The liver and spleen are the most common sites of extramedullary hematopoiesis, but thoracic involvement is likewise observed. Pleural effusions in the setting of intrathoracic extramedullary hematopoiesis have been attributed to mechanical interactions between the pleural surface and neighboring paravertebral masses consisting of hematopoietic tissue. Rupture of these highly vascularized lesions into the adjacent pleural space has been the putative mechanism in cases complicated by hemothorax. Histologically proven instances of islets of extramedullary hematopoiesis occurring on the pleural surface itself are exceedingly rare. Our case of a patient with myelofibrosis and massive pleural effusion is only the third such example described in the literature and the second to result in a confirmed hemothorax requiring surgery. As expected, technetium-99m sulfur (Tc-99m sulfur) colloid scanning accurately localized sites of extramedullary hematopoiesis in our patient, and there was a salutary response to radiation therapy.

Recurrent gene mutations have been described with varying frequencies in myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS). Recent work has placed significant focus on understanding the role of gene lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene encoding critical spliceosomal proteins. SRSF2 mutations appear to play an important role in pathogenesis of MMOS, particularly in chronic myelomonocytic leukemia. Inhibition of splicing may be a new therapeutic approach. E7107, a spliceosome inhibitor, has been shown to differentially inhibit splicing more in SRSF2-mutant cells leading to decreased leukemia burden in mice. H3B-8800 is a small molecule modulator of spliceosome complex and has been shown to lower leukemia burden in SRSF2-P95H mutant mice. This review focuses on the incidence of mutant SRSF2 across various MMOS as well as recent clinical development of spliceosome inhibitors.

Kaposi sarcoma inflammatory cytokine syndrome (KICS) is a newly-described condition affecting individuals who are HIV-positive and are infected with human herpesvirus 8 (HHV-8). This is a syndrome that in some ways mimics severe sepsis with associated acute respiratory distress syndrome, possibly requiring a ventilator and vasopressor support. However, unlike severe sepsis, antibiotics provide no benefit. Management of KICS has not been fully elucidated because of its high mortality rate. However, the syndrome has been successfully treated in some cases with immunomodulatory therapy. It is crucial for oncologists to be able to recognize this syndrome and to institute the appropriate therapy.