A phase 2 trial of a topical antiseptic bundle in head and neck cancer surgery: Effects on surgical site infection and the oral microbiome.

BACKGROUND: Head and neck cancer (HNC) surgery remains an important component of management but is associated with a high rate of surgical site infection (SSI). We aimed to assess the safety and efficacy of a topical mucosal antiseptic bundle in preventing SSI and evaluate microbial predictors of infection through a genomic sequencing approach. METHODS: This study was an open-label, single-arm, single-center, phase 2 trial of a topical mucosal antiseptic bundle in patients with HNC undergoing aerodigestive tract resection and reconstruction. Patients underwent topical preparation of the oral mucosa with povidone-iodine (PI) and chlorhexidine gluconate (CHG) pre- and intra-operatively followed by oral tetracycline ointment every 6 hours for 2 days post-operatively. The primary outcome was change in bacterial bioburden at the oral surgical site. Secondary outcomes included safety, SSI, and microbial predictors of infection. FINDINGS: Of 27 patients screened between January 8, 2021, and May 14, 2021, 26 were enrolled and 25 completed the study. There were no antiseptic-related adverse events. The topical mucosal antiseptic bundle significantly decreased oral bacterial colony-forming units from pre-operative levels (log10 mean difference 4·03, 95%CI 3·13-4·;92). There were three SSI (12%) within 30 days. In correlative genomic studies, a distinct set of amplicon sequence variants in the post-operative microbiome was associated with SSI. Further, despite no instance of post-operative orocervical fistula, metagenomic sequence mapping revealed the oral cavity as the origin of the infectious organism in two of the three SSI. INTERPRETATION: The bacterial strains which subsequently caused SSI were frequently identified in the pre-operative oral cavity. Accordingly, a topical antiseptic bundle decreased oral bacterial bioburden throughout the peri-operative period and was associated with a low rate of SSI, supporting further study of topical antisepsis in HNC surgery. FUNDING: Alliance Oncology.

Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection.

BACKGROUND: Incomplete immune reconstitution may occur despite successful antiretroviral therapy (ART). Gut-associated lymphoid tissue (GALT) fibrosis may contribute via local CD4+ T lymphocyte depletion, intestinal barrier disruption, microbial translocation, and immune activation. METHODS: In a cross-sectional analysis, we measured circulating fibrosis biomarker levels on cryopreserved plasma from adult HIV-infected (HIV+) SCOPE study participants on suppressive ART who also had fibrosis quantification on recto-sigmoid biopsies. Relationships among biomarker levels, clinical and demographic variables, GALT lymphoid aggregate (LA) collagen deposition, and LA CD4+ T lymphocyte density were analyzed using simple regression. Biomarker levels were also compared to levels in HIV+ viremic SCOPE participants and a convenience sample of HIV-uninfected (HIV-) samples. RESULTS: HIV+ aviremic participants (n = 39) were 92% male and 41% non-white, with median age 48 years, CD4+ T lymphocyte count 277 cells/mm3, and 17 years since HIV diagnosis. Most biomarkers were lower in HIV- (n = 36) vs HIV+ aviremic individuals, although CXCL4 levels were higher. HIV+ viremic individuals (N = 18) had higher median TGF-ß3, CIC-C1Q, and TIMP-1 (P < 0.05) and lower LOXL2 levels (P = 0.08) than HIV+ aviremic individuals. Only higher LOXL2 levels correlated with more GALT collagen deposition (R = 0.44, P= 0.008) and lower LA CD4+ T lymphocyte density (R = -0.32, P = 0.05) among aviremic individuals. CONCLUSIONS: Circulating LOXL2 levels may be a noninvasive measure of intestinal fibrosis and GALT CD4+ T lymphocyte depletion in treated HIV infection. LOXL2 crosslinks elastin and collagen, and elevated LOXL2 levels occur in pathologic states, making LOXL2 inhibition a potential interventional target for intestinal fibrosis and its sequelae.

Lysinibacillus massiliensis Panniculitis Masquerading as Erythema Nodosum: A Case Report.

Lysinibacillus massiliensis, formerly Bacillus massiliensis, is an environmental Gram-positive bacillus that is generally non-pathogenic. Rare case reports in immunosuppressed patients have described sepsis with this organism. In this study, we report a case of L massiliensis as a cause of infectious panniculitis mimicking erythema nodosum after infusion of autologous adipose-derived stem cells in an immunosuppressed patient with refractory Crohn's disease. This case highlights the importance of care providers to consider exposures and host factors when interpreting culture results with otherwise benign organisms.

Zika Virus in the Americas: A Review for Clinicians.

Zika virus has recently emerged as a new public health threat. An arthropod-borne virus named after the Zika forest in Uganda, it was first discovered in 1947. The virus caused only sporadic cases of Zika infection in Africa and Southeast Asia until 2007, when the first large outbreak occurred in the Yap State in the Federated States of Micronesia. Another outbreak in French Polynesia in 2013 was notable for being associated temporally with an increase in cases of Guillain-Barré syndrome. In 2015, the virus was first reported in Brazil and since then has spread explosively through several additional countries in South and Central America and the Caribbean. Simultaneously, several of these countries have seen a dramatic increase in the incidence of infants born with microcephaly. The rapid spread of Zika virus through the Americas, together with the association of infection with microcephaly and Guillain-Barré syndrome, has resulted in the World Health Organization declaring a public health emergency. Zika virus has the potential to spread to new areas where the Aedes mosquito vector is present and therefore presents a risk to the United States. This concise review describes the clinical features of Zika virus infection and provides advice for clinicians on counseling travelers and others about the disease.

Clinical Manifestations and Treatment of Lyme Disease.

Lyme disease is the most common tick-borne illness in the United States and is also seen in areas of Europe and Asia. The growing deer and Ixodes species tick populations in many areas underscore the importance of clinicians to properly recognize and treat the different stages of Lyme disease. Controversy regarding the cause and management of persistent symptoms following treatment of Lyme disease persists and is highlighted in this review.

Respiratory Infections in the U.S. Military: Recent Experience and Control.

This comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. Outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morbidity sustained by shipboard personnel at sea, and (iv) experience of deployed personnel. Utilizing a pathogen-by-pathogen approach, we examine (i) epidemiology, (ii) impact in terms of morbidity and operational readiness, (iii) clinical presentation and outbreak potential, (iv) diagnostic modalities, (v) treatment approaches, and (vi) vaccine and other control measures. We also outline military-specific initiatives in (i) surveillance, (ii) vaccine development and policy, (iii) novel influenza and coronavirus diagnostic test development and surveillance methods, (iv) influenza virus transmission and severity prediction modeling efforts, and (v) evaluation and implementation of nonvaccine, nonpharmacologic interventions.

Tuberculosis as a force health protection threat to the United States military.

Tuberculosis (TB) is a communicable disease that poses a threat to force health protection to the U.S. military. The rate of TB disease in the military is low; however, there are unique challenges for its control in this setting. As a low-risk population, TB testing in the U.S. military can be scaled back from the universal testing approach used previously. Reactivation of latent TB infection (LTBI) present at accession into service is the most important factor leading to TB disease; therefore, its diagnosis and treatment among recruits should be given a high priority. Deployment and overseas military service is an uncommon but important source of TB infection, and rigorous surveillance should be ensured. Case management of TB disease and LTBI can be improved by the use of cohort reviews at the service and installation levels and case finding and delays in the diagnosis of TB disease can be improved by education of providers, as well as increased use of molecular diagnostic tests. Program outcomes can be improved by making LTBI treatment compulsory, offering shorter treatment regimens, and increasing accountability through oversight and evaluation. The diagnosis of LTBI can be improved by implementing targeted testing in all settings and reducing confirmatory interferon-gamma release assay testing.

Lymphoid fibrosis occurs in long-term nonprogressors and persists with antiretroviral therapy but may be reversible with curative interventions.

Human immunodeficiency virus (HIV) replication causes lymphoid tissue (LT) fibrosis, which causes CD4(+) T-cell depletion. It is unknown whether people who spontaneously control HIV replication have LT fibrosis. We measured LT fibrosis and CD4(+) T cells in 25 HIV controllers, 10 noncontrollers, 45 HIV-positive individuals receiving therapy, and 10 HIV-negative individuals. Controllers had significant LT fibrosis and CD4(+) T-cell depletion, similar to noncontrollers, but the so-called Berlin patient (in whom HIV infection was cured) had near normal LT. Thus, LT fibrosis occurs in all HIV-infected subjects, and current therapy does not reverse it. Reversal of fibrosis during a curative intervention suggests that ongoing low-level virus production may maintain LT fibrosis.