Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis.

BACKGROUND: People living with HIV (PLWH) have increased risk of developing cancers after controlling traditional risk factors and viral suppression. This study explores whether T cells can serve as a marker of risk for cancer among HIV-infected virally suppressed patients. METHODS: A nested case control study design was pursued with 17 cancer cases and 73 controls (PLWH without cancer)ouidentified among the US Military HIV Natural History Study cohort, and were matched for CD4 + count, duration of HIV infection, and viral suppression. Cells were obtained from PLWH on an average of 12 months prior to clinical cancer diagnosis. Expression of inhibitory receptors (PD-1, CD160, CD244, Lag-3, and TIGIT), and transcription factors (T-bet, Eomesodermin, TCF-1, and (TOX) was measured on CD8 +T cells from that early time point. RESULTS: We found that cases have increased expression of PD-1 +CD160+CD244+ ('triple positive') on total and effector CD8 + compared with controls (p=0.02). Furthermore, CD8 +T cells that were both PD-1 +CD160+CD244+ and T-betdimEomeshi were significantly elevated in cases at time point before cancer detection, compared with controls without cancer (p=0.008). This was driven by the finding that transcriptional factor profile of cells was altered in cancers compared with controls. Triple-positive cells were noted to retain the ability for cytotoxicity and cytokine secretion mediated by expression of CD160 and PD-1, respectively. However, triple-positive cells demonstrated high expression of TOX-1, a transcription factor associated with T cell exhaustion. CONCLUSION: In conclusion, we have found a subset of dysfunctional CD8 +T cells, PD-1 +CD160+CD244+T-betdimEomeshi, that is elevated 12 months before cancer diagnosis, suggesting that peripheral T cell alterations may serve as a biomarker of increased cancer risk among PLWH.

Correlation of culture with histopathology in fungal burn wound colonization and infection.

An increasing number of burn wound infections are now due to fungi. Historically, therapy of fungal burn wound infections (FWI) consisted of debridement, topical antifungals and/or IV amphotericin B, negating the need to categorize disease further than fungal burn wound colonization (FWC) versus FWI. Newer antifungal agents have varying spectrums of activity, increasing the importance of identifying fungi, often to species. The records of patients admitted to our burn center from April 2000 to March 2005 were reviewed for fungi identified by histopathology. Wound specimens with fungi were classified as FWC or FWI and culture results were compared. The 1515 surgical wound tissue specimens were obtained from 2036 patients. Fungi were detected in the histopathology of 68 patients, 19 with FWI (3.8FWI/year); 9 had corresponding growth on culture. Forty nine patients were identified with FWC, 16 with fungi recovered in corresponding cultures. FWI was associated with increased mortality (OR 25.3, CI 3.12-204.8). Correlation between histopathologic and culture identification of fungi was inconsistent. The etiology of FWI was diverse; fungi with known resistance to each of the three major classes of antifungals were isolated, suggesting empirical use of one class may be inadequate to treat FWI. Future burn wound management must seek to identify fungal pathogens to species.

Type-specific clinical characteristics of adenovirus-associated influenza-like illness at five US military medical centers, 2009-2014.

BACKGROUND: Adenovirus is a recognized cause of influenza-like illness (ILI). The proportion of ILI attributable to adenovirus is not known. Moreover, knowledge gaps remain with respect to the epidemiologic, virologic, and clinical characteristics of adenovirus-associated ILI among otherwise healthy individuals. METHODS: An observational, longitudinal study of <65-year-old patients with febrile ILI at five medical centers was conducted from 2009 to 2014. Nasopharyngeal specimens obtained at enrollment were first tested by single-reaction PCR for adenovirus, then further evaluated by a multiplex PCR assay for other respiratory viral pathogens. Symptoms over a 28-day period were collected. RESULTS: We enrolled 1536 individuals, among whom 43 (2·8%) were positive for adenovirus. The median age of cases was 3·4 years (range: 4 months to 41 years). Three were hospitalized. Species and serotype information was available for 33 (76·7%) cases. Species C (n = 21) was the most common, followed by B3 (n = 9) and one each of E4a, D46, and A. Species C infections were more frequent in children (P < 0·01). Half of the cases were positive for at least one other respiratory viral pathogen. Symptoms were generally mild and most commonly included cough (90%), fatigue (79%), rhinorrhea (74%), loss of appetite (71%), and sore throat (64%). Children with non-C adenovirus infection were more likely to report sore throat (P = 0·05) and hoarseness (P = 0·06) than those with species C infection. CONCLUSIONS: Adenovirus is frequently detected with other respiratory viruses. Persons with non-C adenovirus infections reported more severe symptoms, suggesting there may be species-specific differences in virulence and/or host response to infection.

An End-of-Year Oral Examination for Internal Medicine Residents: An Assessment Tool for the Clinical Competency Committee.

BACKGROUND: Comprehensive evaluations of clinical competency consume a large amount of time and resources. An oral examination is a unique evaluation tool that can augment a global performance assessment by the Clinical Competency Committee (CCC). OBJECTIVE: We developed an oral examination to aid our CCC in evaluating resident performance. METHODS: We reviewed tools used in our internal medicine residency program and other training programs in our institution. A literature search failed to identify reports of a similar evaluation tool used in internal medicine programs. We developed and administered an internal medicine oral examination (IMOE) to our postgraduate year-1 and postgraduate year-2 internal medicine residents annually over a 3-year period. The results were used to enhance our CCC's discussion of overall resident performance. We estimated the costs in terms of faculty time away from patient care activities. RESULTS: Of the 54 residents, 46 (86%) passed the IMOE on their first attempt. Of the 8 (14%) residents who failed, all but 1 successfully passed after a mentored study period and retest. Less than 0.1 annual full-time equivalent per faculty member was committed by most faculty involved, and the time spent on the IMOE replaced regular resident daily conference activities. CONCLUSIONS: The results of the IMOE were added to other assessment tools and used by the CCC for a global assessment of resident performance. An oral examination is feasible in terms of cost and can be easily modified to fit the needs of various competency committees.

Pneumocystis pneumonia.

Pneumocystis is an opportunistic fungus that is a major cause of morbidity and mortality in immunocompromised hosts. Despite a decline in incidence with the advent of highly active antiretroviral therapy (HAART), Pneumocystis remains the most common opportunistic infection in patients with the acquired immunodeficiency syndrome (AIDS) and is an increasing cause of disease in patients with other forms of immunosuppression. Although there have been advances in the prevention and treatment of this infection, the mortality for Pneumocystis pneumonia (PCP) in the setting of AIDS remains 10 to 20%. The mortality for patients with other forms of immunosuppression is poorly defined but may actually be higher than that reported in the setting of AIDS. The continued severity of PCP in the AIDS population, its increasing frequency in other immunosuppressed populations, and increasing evidence that normal hosts may serve as a reservoir for the organism merit continued evaluation of the epidemiology, clinical presentation, diagnosis, and treatment of this infection.