Relationship between Civilian Injuries Caused during Contact with Law Enforcement and Community-Level Sociodemographic Characteristics.

Civilian injuries caused during contact with law enforcement personnel erode community trust in policing, impact individual well-being, and exacerbate existing health inequities. We assessed the relationship between ZIP code-level rates of civilian injuries caused during legal interventions and community-level sociodemographic characteristics using Illinois hospital data from 2016 to 2022. We developed multivariable Poisson regression models to examine whether legal intervention injury rates differed by race-ethnicity and community economic disadvantage across three geographic regions of Illinois representing different levels of urbanization. Over the study period, 4976 civilian injuries were treated in Illinois hospitals (rate of 5.6 per 100,000 residents). Compared to non-Hispanic white residents, non-Hispanic Black residents demonstrated 5.5-10.5 times higher injury rates across the three geographic regions, and Hispanic-Latino residents demonstrated higher rates in Chicago and suburban Cook County, but lower rates in the rest of the state. In most regions, models showed that as the percent of minority residents in a ZIP code increased, injury rates among non-Hispanic Black and Hispanic-Latino residents decreased. As community economic disadvantage increased at the ZIP code level, civilian injury rates increased. Communities with the highest injury rates involving non-Hispanic white residents were significantly more economically unequal and disadvantaged. While the injury rates were consistently and substantially higher among non-Hispanic Black residents throughout the state, the findings illustrate that the association between overall civilian injuries caused during contact with law enforcement and community sociodemographic characteristics varied across regions. Data on local law enforcement agency policies and procedures are needed to better identify appropriate interventions.

Characterising the Aboriginal and Torres Strait Islander patient journey after a serious road traffic injury and barriers to access to compensation: a protocol.

INTRODUCTION: Road safety has been a long-enduring policy concern in Australia, with significant financial burden of road trauma and evident socioeconomic disparities. Transport injuries disproportionately impact individuals in remote areas, those in lower socioeconomic situations, and Aboriginal and Torres Strait Islander populations. There is a lack of insight into transport injuries in Aboriginal and Torres Strait Islander communities, absence of Indigenous perspective in published research and limited utilisation of linked data assets to address the inequity. Aim 1 is to determine the breadth, cost and causal factors of serious injury from road traffic crashes in South Australia (SA) and New South Wales (NSW) with a focus on injury prevention. Aim 2 is to identify enablers and barriers to compensation schemes for Aboriginal and Torres Strait Islander patients in SA and NSW. METHODS AND ANALYSIS: This study will be guided by an Aboriginal and Torres Strait Islander Governance Group, applying Knowledge Interface Methodology and Indigenous research principles to ensure Indigenous Data Sovereignty and incorporation of informed perspectives. A mixed-method approach will be undertaken to explore study aims including using big data assets and mapping patient journey. CONCLUSION: The results of this study will provide valuable insights for the development of focused injury prevention strategies and policies tailored to Aboriginal and Torres Strait Islander communities. By addressing the specific needs and challenges faced by these communities, the study aims to enhance road safety outcomes and promote equitable access to healthcare and compensation for affected individuals and their families.

Is an Orthopaedic Surgery Resident's Previous Case Experience Associated with Success of Initial Treatment of Pediatric Forearm Fractures?

Redisplacement and subsequent intervention are common for pediatric forearm fractures. We investigated associations between the success of closed reduction and the treating provider's experience. We identified patients aged 4-16 years with forearm fractures treated by closed reduction and cast immobilization. Clinical data and radiographs of 130 patients treated by 30 residents were reviewed to determine the treating resident's pediatric forearm fracture reduction experience and the incidence of initial treatment failure (ITF). ITF was defined as subsequent intervention before union or malunion. ITF occurred in 32 of 130 patients (25%), comprising 12 of 23 patients (52%) treated by residents with no previous experience and 20 of 107 patients (19%) treated by residents who had logged ≥ 1 previous reduction (odds ratio, 4.7). ITF was more likely to occur in pediatric forearm fractures treated by residents with no previous forearm reduction experience compared with those performed by residents who had such experience. Level of Evidence: Level III, therapeutic. (Journal of Surgical Orthopaedic Advances 32(1):032-035, 2023).

Poor adherence to dust, noise and safety regulations predict injury rates in underground coal mines.

BACKGROUND: While safety in US coal mining has improved over the past two decades, general occupational health research shows that risk of injury varies across individual worksites and is influenced by worksite safety cultures and practices. METHODS: In this longitudinal study, we evaluated whether mine-level characteristics reflecting poor adherence to health and safety regulations in underground coal mines are associated with higher acute injury rates. We aggregated Mine Safety and Health Administration (MSHA) data by year for each underground coal mine for the period 2000-2019. Data included part-50 injuries, mine characteristics, employment and production, dust sampling, noise sampling, and violations. Multivariable hierarchical generalised estimating equations (GEE) models were developed. RESULTS: Based on the final GEE model, despite an average annual decline in injury rates by 5.5%, the following indicators of inadequate adherence to health and safety regulations were associated with increased average annual injury rates: +2.9% for each 10% increase in dust samples exceeding the permissible exposure limit; +0.6% for each 10% increase of permitted 90 dBA 8-hour noise exposure dose; +2.0% for every 10 substantial-significant MSHA violations in a year; +1.8% for each rescue/recovery procedure violation; +2.6% for each safeguard violation. If a fatality occurred in a mine, injury rates increased by 11.9% in the same year, but declined by 10.4% in the following year. The presence of safety committees was associated with a 14.5% decline in injury rates. DISCUSSION: In US underground coal mines, injury rates are associated with poor adherence to dust, noise and safety regulations.

Trends in assault-related hospitalizations during the SARS-CoV-2 pandemic.

INTRODUCTION: Violence remains a priority issue in the United States (US) requiring public health input to discern the magnitude and impact of violence on the health system. Concerns over violence and the injuries resulting from violence have increased following the SARS-CoV-2 pandemic which exacerbated an array of individual and economic stressors related to violence including increased unemployment, alcohol intake, social isolation, anxiety and panic and decreased access to health services. The aim of this study was to analyze the trends in violence-related injuries in the state of Illinois during the SARS-CoV-2 lockdown periods and post-lockdown in order to inform future public health policy. MATERIAL AND METHODS: Outpatient and inpatient assault related injuries treated in Illinois hospitals from 2016 through March 2022 were analyzed. Segmented regression models evaluating change in time trends were adjusted for seasonality, serial correlation, overall trend and economic variables. RESULTS: The annual rate of assault related hospitalizations per one million Illinois residents decreased from 3857.8 pre-pandemic to 3458.7 pandemic period. However, during the pandemic there was an increase in deaths and in the proportion of injuries involving open wounds, internal injuries, and fractures, while there was a reduction in less serious injuries. Segmented regression time series models demonstrated significant increase in firearm violence in all four pandemic periods examined. Firearm violence increased particularly in subgroups including African-American victims, 15-34-year-olds, and Chicago residents. CONCLUSION: During SARS-CoV-2, we saw an overall reduction in assault related hospitalization, however, findings demonstrated an increase in serious injuries which may be associated with social and economic stressors of the pandemic, increased gun-violence while decrease in less serious injuries may be linked to hospital avoidance for non-lethal injuries during the peak waves of the pandemic. Our findings have implications for ongoing surveillance, service planning and management of the increased gunshot and penetrating assault cases and further demonstrate the need for public health input into the violence epidemic in the US.

Characterization of lipomatous tumors with high-resolution 1H MRS at 17.6T: Do benign lipomas, atypical lipomatous tumors and liposarcomas have a distinct metabolic signature?

Background: Distinguishing between some benign lipomas (BLs), atypical lipomatous tumors (ALTs), and dedifferentiated liposarcomas (DDLs) can be challenging due to overlapping magnetic resonance imaging characteristics, and poorly understood molecular mechanisms underlying the malignant transformation of liposarcomas. Purpose: To identify metabolic biomarkers of the lipomatous tumor spectrum by examining human tissue specimens using high-resolution 1H magnetic resonance spectroscopy (MRS). Materials and methods: In this prospective study, human tissue specimens were obtained from participants who underwent surgical resection for radiologically-indeterminate lipomatous tumors between November 2016 and May 2019. Tissue specimens were obtained from normal subcutaneous fat (n=9), BLs (n=10), ALTs (n=7) and DDLs (n=8). Extracts from specimens were examined with high-resolution MRS at 17.6T. Computational modeling of pattern recognition-based cluster analysis was utilized to identify significant differences in metabolic signatures between the lipomatous tumor types. Results: Significant differences between BLs and ALTs were observed for multiple metabolites, including leucine, valine, branched chain amino acids, alanine, acetate, glutamine, and formate. DDLs were distinguished from ALTs by increased glucose and lactate, and increased phosphatidylcholine. Multivariate principal component analysis showed clear clustering identifying distinct metabolic signatures of the tissue types. Conclusion: Metabolic signatures identified in 1H MR spectra of lipomatous tumors provide new insights into malignant progression and metabolic targeting. The metabolic patterns identified provide the foundation of developing noninvasive MRS or PET imaging biomarkers to distinguish between BLs, ALTs, and DDLs.

Systematic scoping review of occupational health injuries and illnesses among Indigenous workers.

Indigenous populations in the USA, Australia, New Zealand (NZ) and Canada total more than 13 million, but continue to be marginalised in their respective regions. The goal of this comprehensive review of all studies evaluating adverse occupational health outcomes among Indigenous populations in these countries was to identify gaps in the literature and future research directions. A systematic scoping review of research published between 1970 and 2020 was undertaken using the methodological framework initially proposed by Arksey and O'Malley. Country, Indigenous participants, study type, exposure, adverse health outcome, occupation and industry were identified for each paper. Of the 1272 research papers identified, only 51 articles met the inclusion criteria of this scoping review. Almost half of the studies (n=24, 47.1%) were published after 2010. Only 13 (25.5%) studies specifically focused on Indigenous persons at the time of the study design, and less than half of the studies (47.1%) included more than 100 Indigenous participants. Most studies used the following general terms without mention of specific indigenous groups: Indigenous (Australia), Maori (NZ), Aboriginal (Canada) and American Indian or Alaskan Native (USA). Only one study acknowledged asking respondents their preferred terminology. Over the past 50 years, there has been a paucity of research directly or indirectly evaluating occupational health outcomes of Indigenous populations in these four countries. There is a need for better sampling strategies and inclusion of demographic questions that capture Indigenous status in surveys, workers' compensation data and other commonly used data sources to develop adequate baseline data for targeted future interventions.

Do contrast-enhanced and advanced MRI sequences improve diagnostic accuracy for indeterminate lipomatous tumors?

PURPOSE: Benign, intermediate-grade and malignant tumors sometimes have overlapping imaging and clinical characteristics. The purpose of this study was to evaluate the added value of contrast-enhanced sequences (dynamic contrast enhancement (DCE)), diffusion-weighted imaging (DWI), and chemical shift imaging (CSI) to noncontrast MRI sequences for the characterization of indeterminate lipomatous tumors. MATERIALS AND METHODS: Thirty-two consecutive patients with histologically proven peripheral lipomatous tumors were retrospectively evaluated. Two musculoskeletal radiologists recorded the MRI features in three sessions: (1) with noncontrast T1-weighted and fluid-sensitive sequences; (2) with addition of static pre- and post-contrast 3D volumetric T1-weighted sequences; and (3) with addition of DCE, DWI, and CSI. After each session, readers recorded a diagnosis (benign, intermediate/atypical lipomatous tumor (ALT), or malignant/dedifferentiated liposarcoma (DDL)). Categorical imaging features (presence of septations, nodules, contrast enhancement) and quantitative metrics (apparent diffusion coefficient values, CSI signal loss) were recorded. RESULTS: For 32 tumors, the diagnostic accuracy of both readers did not improve with the addition of contrast-enhanced sequences, DWI, or CSI (53% (17/32) session 1; 50% (16/30) session 2; 53% (17/32) session 3). Noncontrast features, including thick septations (p = 0.025) and nodules ≥ 1 cm (p < 0.001), were useful for differentiating benign tumors from ALTs and DDLs, as were DWI (p = 0.01) and CSI (p = 0.009) metrics. CONCLUSION: The addition of contrast-enhanced sequences (static, DCE), DWI, and CSI to a conventional, noncontrast MRI protocol did not improve diagnostic accuracy for differentiating benign, intermediate-grade, and malignant lipomatous tumors. However, we identified potentially useful imaging features by DCE, DWI, and CSI that may help distinguish these entities.

Preoperative Considerations for Teenagers Undergoing Orthopaedic Surgery: VTE Prevention, Mental Health Assessment, Vaping, and Drug Addiction.

INTRODUCTION: Adolescents undergoing pediatric orthopaedic surgery typically experience an uncomplicated postoperative course. However, adolescence represents a unique transition period from pediatric to adult physiology. As a result, the astute pediatric orthopaedic surgeon will be aware of unique medical and social scenarios which are relevant to adolescents during the perioperative course including the risk of venous thromboembolism (VTE), prevalence of mental health conditions, and rising use of electronic cigarettes or "vaping" to consume nicotine and cannibas. DISCUSSION: Adolescents are at a greater risk of VTE after pediatric orthopaedic surgery. In particular, adolescent females with a family history of blood clotting disorders and those with a change in mobility after surgery should be considered for prophylaxis. The prevalence of adolescent mental health conditions including anxiety, depression, and behavioral issues is increasing in the United States. Higher levels of preoperative anxiety and the presence of mental health pathology are associated with slower recovery, higher levels of postoperative pain, and the increased likelihood for chronic pain. Several quick screening instruments are available to assess adolescents for preoperative anxiety risk, including the Visual Analogue Scale for Anxiety or the Amsterdam Perioperative Anxiety Information Scale. Unfortunately, electronic cigarettes have become increasingly popular for the consumption of nicotine and cannabis among adolescents. Preoperative use of combustive cigarettes (nicotine/cannabis) represents perioperative risks for induction/anesthesia, postoperative pain, and analgesia requirements and issues with delayed wound and fracture healing. CONCLUSIONS: VTE, underlying mental health conditions, and usage of nicotine and cannabis are clear detriments to the recovery and healing of adolescent patients following orthopaedic surgery. Therefore, standardized screening for adolescents before orthopaedic surgery is indicated to identify perioperative risk factors which have negative impacts on functional outcomes.

Rapid review of five years of Aboriginal and Torres Strait Islander health research in Australia - persisting under-representation of urban populations.

OBJECTIVE: To review how published Aboriginal and Torres Strait Islander health research reflects the geographical distribution of the Indigenous population of Australia. METHODS: Rapid review using Lowitja Institute Lit.search tool for PubMed indexed Indigenous health research papers (January 2013 to January 2018). Geographic location, participant age, study type and recruitment site were identified for each paper. RESULTS: A total of 1,258 research papers were identified: 190 (15%) focused exclusively on Indigenous people living in urban areas; 563 (45%) in rural/remote areas; and 505 (40%) spanned urban and rural/remote areas. Despite similar burdens of disease, three times as many papers were published per 1,000 DALYs for rural/remote areas than urban areas. CONCLUSIONS: Indigenous health research publications have more than doubled since 2010. However, research focusing on the health needs of urban Indigenous people remains low relative to disease burden and population. Implications for public health: More research to address the health needs of Indigenous people living in urban areas is required although this should not be at the expense of research for rural and remote areas. Increased funding quarantined for Indigenous health research, coupled with self-determination of the research agenda and reporting on the geographic representativeness of research, may help address geographical inequities in research outputs.

Knee Scooter-Related Injuries: A Survey of Foot and Ankle Orthopedic Surgeons.

BACKGROUND: Knee scooters ("scooters") are a commonly used device to facilitate postoperative adherence to weightbearing restrictions. Although high rates of falls have been reported, little is known about injuries related to scooter use. METHODS: We analyzed survey responses from 316 of 2046 members (15%) of the American Orthopaedic Foot & Ankle Society in May-June 2019 describing (1) frequency of scooter recommendation; (2) indications for which they recommended scooters; (3) characteristics of patients for whom they recommended scooters; (4) prevalence, anatomic locations, mechanisms, and sequelae of scooter-related injuries; and (5) characteristics of patients with scooter-related injuries. Descriptive statistics and χ2 goodness-of-fit tests were performed (alpha = .05). RESULTS: Mean frequency with which respondents recommended scooters in particular was 69%. Respondents most often recommended scooters after hindfoot arthrodesis (97% [305/316]), ankle arthrodesis (96% [302/316]), and for total nonweightbearing (64% [202/316]) and to patients who were overweight (vs obese) or aged 45-75 years. Mean prevalence of scooter-related injuries was 2.5%. The most common injury mechanism was making a sharp turn (reported by 62% [103/166]). Thirty-four percent (56/166) of respondents with injured patients said patients underwent surgery to treat scooter-related injuries. Patients with scooter-related injuries were more often women, >44 years old, obese, and sedentary. CONCLUSION: Scooters were commonly recommended postoperatively, most often for total nonweightbearing after hindfoot or ankle arthrodesis, and most often in overweight adults or those aged 45-75 years. Mean reported prevalence of scooter-related injuries was 2.5%. Female sex, older age, obesity, and sedentary lifestyle were associated with scooter-related injury. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Surgical Hip Dislocation Using the Modified Hardinge Approach for Excision of Osteocartilaginous Lesions of the Acetabulum and Femoral Neck in an Adult: A Case Report.

CASE: A 20-year-old woman presented with hip pain related to an osteocartilaginous lesion arising within the cotyloid fossa. She also had a lesion along the inferior femoral neck. Resection of both lesions was performed with surgical hip dislocation through a modified Hardinge approach. CONCLUSIONS: This unusual location for an osteocartilaginous lesion can lead to substantial pain and disability. Surgical dislocation through a modified Hardinge approach is an excellent option to concurrently resect these benign lesions of the cotyloid fossa and femoral neck without the need for trochanteric osteotomy.

Impact of Standard Bacterial Vaginosis Treatment on the Genital Microbiota, Immune Milieu, and Ex Vivo Human Immunodeficiency Virus Susceptibility.

BACKGROUND: Genital immunology is a key determinant of human immunodeficiency virus (HIV) susceptibility. Both factors are modulated by bacterial vaginosis (BV) and, to some extent, by Lactobacillus iners, the genital Lactobacillus spp. that predominates in African, Caribbean, and other Black (ACB) women. We conducted a clinical trial to assess the impact of oral metronidazole treatment on the genital immune parameters of HIV acquisition risks in Kenyan women with BV. METHODS: The primary endpoint was ex vivo cervical CD4+ T-cell HIV susceptibility after 1 month; secondary endpoints included genital cytokine/chemokine levels, cervical immune cell populations, and the composition of the cervico-vaginal microbiota by 16S ribosomal RNA gene amplicon sequencing. RESULTS: BV resolved (Nugent score ≤ 3) at 1 month in 20/45 participants, and cervical CD4+ T-cell HIV entry was moderately reduced in all participants, regardless of treatment outcome. Resolution of BV and reduced abundances of BV-associated gram-negative taxa correlated with reduced genital interleukin (IL)-1α/ß. However, BV resolution and the concomitant colonization by Lactobacillus iners substantially increased several genital chemokines associated with HIV acquisition, including interferon-γ inducible protein (IP)-10, macrophage inflammatory protein (MIP)-3α, and monokine induced by gamma interferon (MIG). In an independent cohort of ACB women, most of whom were BV-free, vaginal chemokines were again closely linked with L. iners abundance, though not other Lactobacillus spp. CONCLUSIONS: BV treatment reduced genital CD4+ T-cell HIV susceptibility and IL-1 levels, but dramatically increased the genital chemokines that may enhance HIV susceptibility; the latter effect was related to the restoration of an Lactobacillus iners-dominated microbiota. Further studies are needed before treatment of asymptomatic BV can be recommended for HIV prevention in ACB communities.

Treatment of a Pediatric T-type Intercondylar Humerus Fracture With Hybrid Percutaneous Pinning and External Fixation.

T-type intercondylar fractures of the distal humerus are rare injuries in skeletally immature patients. Few studies are available to guide the treatment of these injuries. Small case series and expert recommendations suggest superiority of the open approach for direct reduction of the articular surface. This approach poses risks of vascular compromise and elbow stiffness. However, success with percutaneous intercondylar screw fixation has been described for simple split patterns. The authors present a case that illustrates a novel percutaneous technique to treat this fracture type. A healthy 8-year-old boy sustained a T-type intercondylar fracture of the distal humerus (AO 13-C1). Excellent reduction was noted after closed reduction and crossed percutaneous pinning. Compression was applied across the pins through a small external fixator bar to address the intercondylar split component. At the 6-week postoperative clinic visit, the pins and fixator were removed uneventfully, and normal healing with full range of elbow motion was noted. This case report describes a simple, minimally invasive technique to treat uncomplicated T-type intercondylar fractures of the distal humerus in skeletally immature patients. Practitioners familiar with percutaneous fixation of supracondylar fractures can easily perform this technique. The described technique spares an open dissection and avoids permanent implants around the joint. Further multicenter research is warranted to determine the long-term outcomes and safety of the described technique. [Orthopedics. 2017; 40(6):e1096-e1098.].

Chemokine Levels in the Penile Coronal Sulcus Correlate with HIV-1 Acquisition and Are Reduced by Male Circumcision in Rakai, Uganda.

Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology to measure levels of seven cytokines in coronal sulcus (penile) swabs collected longitudinally from initially uncircumcised men enrolled in a randomized trial of circumcision in Rakai, Uganda. Coronal sulcus cytokine levels were compared between men who acquired HIV and controls who remained seronegative. Cytokines were also compared within men before and after circumcision, and correlated with CD4 T cells subsets in foreskin tissue. HIV acquisition was associated with detectable coronal sulcus Interleukin-8 (IL-8 aOR 2.26, 95%CI 1.04-6.40) and Monokine Induced by γ-interferon (MIG aOR 2.72, 95%CI 1.15-8.06) at the visit prior to seroconversion, and the odds of seroconversion increased with detection of multiple cytokines. Coronal sulcus chemokine levels were not correlated with those in the vagina of a man's female sex partner. The detection of IL-8 in swabs was significantly reduced 6 months after circumcision (PRR 0.59, 95%CI 0.44-0.87), and continued to decline for at least two years (PRR 0.29, 95%CI 0.16-0.54). Finally, prepuce IL-8 correlated with increased HIV target cell density in foreskin tissues, including highly susceptible CD4 T cells subsets, as well as with tissue neutrophil density. Together, these data suggest that penile inflammation increases HIV susceptibility and is reduced by circumcision.

Evaluation and management of the pregnant patient with suspected primary musculoskeletal tumor or metastatic carcinoma to bone.

Primary musculoskeletal cancer and metastatic disease to bone in pregnant patients presents major treatment challenges. Although uncommon, musculoskeletal malignancies in pregnant women have been reported. When diagnosing and treating these patients, the mother's health must be managed appropriately while ensuring that fetal development is not deleteriously affected. Extensive radiographic imaging and more advanced techniques are often necessary to fully characterize the extent of disease. When possible, magnetic resonance imaging should be used instead of computed tomography to limit exposure of the conceptus to radiation. If treatment is needed, therapeutic radiation, chemotherapy, and surgery should be considered. Surgical resection is the foundation of treatment of early-stage primary bone tumors and soft-tissue sarcomas during pregnancy. With surgery, anesthesia and thromboprophylaxis are important considerations. If chemotherapy is required, administration should be avoided in the first trimester to limit harm to the fetus. Therapeutic radiation should similarly be avoided during the first trimester and often can be postponed until after delivery.

Effect of Intercurrent Infections and Vaccinations on Immune and Inflammatory Biomarkers Among Human Immunodeficiency Virus-Infected Adults on Suppressive Antiretroviral Therapy.

We used generalized estimating equations to quantify the impact of recent vaccination or intercurrent infections on immune and inflammatory biomarkers among 144 human immunodeficiency virus (HIV)-infected adults with HIV RNA < 50 copies/mL on antiretroviral therapy. These events were associated with a 2.244 µg/mL increase in high sensitivity C-reactive protein and should be routinely assessed in future studies.

Inflammation and HIV Transmission in Sub-Saharan Africa.

While the per-contact risk of sexual HIV transmission is relatively low, it is fourfold higher in sub-Saharan Africa, and this may partly explain the major global disparities that exist in HIV prevalence. Genital immune parameters are key determinants of HIV transmission risk, including epithelial integrity and the presence of highly HIV-susceptible intraepithelial or submucosal CD4+ T cell target cells. Biological parameters that may enhance mucosal HIV susceptibility in highly HIV-affected regions of sub-Saharan Africa include increased levels of mucosal inflammation, which can affect both epithelial integrity and target cell availability, as well as the increased mucosal surface area that is afforded by an intact foreskin, contraceptive choices, and intravaginal practices. There are multifactorial causes for increased mucosal inflammation, with the prevalence and nature of common co-infections being particularly relevant.

Herpes simplex virus type 2 serostatus is not associated with inflammatory or metabolic markers in antiretroviral therapy-treated HIV.

Systemic inflammation and immune activation may persist in HIV-infected persons on suppressive combination antiretroviral therapy (cART) and contribute to adverse health outcomes. We compared markers of immune activation, inflammation, and abnormal glucose and lipid metabolism in HIV-infected adults according to herpes simplex virus type 2 (HSV-2) serostatus in a 6-month observational cohort study in Toronto, Canada. HIV-infected adults on suppressive (viral load <50 copies/ml) cART were categorized as HSV-2 seropositive or seronegative using the HerpeSelect ELISA, and underwent study visits at baseline, 3 months, and 6 months. The primary outcome was the median percentage of activated (CD38(+)HLADR(+)) CD8 T cells. Secondary outcome measures included additional immune (activated CD4, regulatory T cells) and inflammatory (hsCRP, D-dimer, IL-1b, IL-6, MCP-1, TNF, sICAM-1, sVCAM-1, Ang1/Ang2 ratio) markers. Metabolic outcomes included the proportion with impaired fasting glucose/impaired glucose tolerance/diabetes, insulin sensitivity (calculated using the Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and fasting lipids. The impact of HSV-2 on each outcome was estimated using generalized estimating equation regression models. Of 84 participants, 38 (45%) were HSV-2 seropositive. HSV signs and symptoms were uncommon. Aside from D-dimer, which was more often detectable in HSV-2 seropositives (adjusted odds ratio=3.58, 95% CI=1.27, 10.07), HSV-2 serostatus was not associated with differences in any other immune, inflammatory cytokine, acute phase reactant, endothelial activation, or metabolic markers examined in univariable or multivariable models. During the study, CD8 and CD4 T cell activation declined by 0.16% and 0.08% per month, respectively, while regulatory T cells increased by 0.05% per month. HSV-2 serostatus was not consistently associated with immune activation, inflammatory, or lipid and glucose metabolic markers in this cohort of HIV-infected adults on suppressive cART.

Impact of asymptomatic herpes simplex virus type 2 infection on mucosal homing and immune cell subsets in the blood and female genital tract.

HSV-2 infection is common and generally asymptomatic, but it is associated with increased HIV susceptibility and disease progression. This may relate to herpes-mediated changes in genital and systemic immunology. Cervical cytobrushes and blood were collected from HIV-uninfected African/Caribbean women in Toronto, and immune cell subsets were enumerated blindly by flow cytometry. Immune differences between groups were assessed by univariate analysis and confirmed using a multivariate model. Study participants consisted of 46 women, of whom 54% were infected with HSV-2. T cell activation and expression of the mucosal homing integrin α4ß7 (19.60 versus 8.76%; p < 0.001) were increased in the blood of HSV-2-infected women. Furthermore, expression of α4ß7 on blood T cells correlated with increased numbers of activated (coexpressing CD38/HLA-DR; p = 0.004) and CCR5(+) (p = 0.005) cervical CD4(+) T cells. HSV-2-infected women exhibited an increase in the number of cervical CD4(+) T cells (715 versus 262 cells/cytobrush; p = 0.016), as well as an increase in the number and proportion of cervical CD4(+) T cells that expressed CCR5(+) (406 versus 131 cells, p = 0.001; and 50.70 versus 34.90%, p = 0.004) and were activated (112 versus 13 cells, p < 0.001; and 9.84 versus 4.86%, p = 0.009). Mannose receptor expression also was increased on cervical dendritic cell subsets. In conclusion, asymptomatic HSV-2 infection was associated with significant systemic and genital immune changes, including increased immune activation and systemic α4ß7 expression; correlation of the latter with highly HIV-susceptible CD4(+) T cell subsets in the cervix may provide a mechanism for the increased HIV susceptibility observed in asymptomatic HSV-2-infected women.