Tissue remodeling by an opportunistic pathogen triggers allergic inflammation.

Different effector arms of the immune system are optimized to protect from different classes of pathogens. In some cases, pathogens manipulate the host immune system to promote the wrong type of effector response-a phenomenon known as immune deviation. Typically, immune deviation helps pathogens to avoid destructive immune responses. Here, we report on a type of immune deviation whereby an opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa), induces the type 2 immune response resulting in mucin production that is used as an energy source by the pathogen. Specifically, P. aeruginosa-secreted toxin, LasB, processed and activated epithelial amphiregulin to induce type 2 inflammation and mucin production. This "niche remodeling" by P. aeruginosa promoted colonization and, as a by-product, allergic sensitization. Our study thus reveals a type of bacterial immune deviation by increasing nutrient supply. It also uncovers a mechanism of allergic sensitization by a bacterial virulence factor.

Mpox: The Reemergence of an Old Disease and Inequities.

Mpox, previously known as monkeypox, is caused by an Orthopoxvirus related to the variola virus that causes smallpox. Prior to 2022, mpox was considered a zoonotic disease endemic to central and west Africa. Since May 2022, more than 86,000 cases of mpox from 110 countries have been identified across the world, predominantly in men who have sex with men, most often acquired through close physical contact or during sexual activity. The classical clinical presentation of mpox is a prodrome including fever, lethargy, and lymphadenopathy followed by a characteristic vesiculopustular rash. The recent 2022 outbreak included novel presentations of mpox with a predominance of anogenital lesions, mucosal lesions, and other features such as anorectal pain, proctitis, oropharyngeal lesions, tonsillitis, and multiphasic skin lesions. We describe the demographics and clinical spectrum of classical and novel mpox, outlining the potential complications and management.

The ephemeral record: The role of opportunistic animal resources in the archaeology of Pampa and Patagonia.

The acquisition of opportunistic animal resources by hunter-gatherers-such as scavenged carcasses-is a well-known subsistence strategy. It is frequently mentioned in the context of the history of early human evolution, but not regularly considered among the strategies utilized by more recent foragers of the Southern Cone of South America. Historical and ethnographic information presented here suggests that the use of opportunistic animal resources was a strategy used under a number of conditions but only partially documented in the archaeological literature. We also present archaeological evidence from four sites-Guardia del Río, Paso Otero 1, Ponsonby, and Myren-in different Pampean and Patagonian settings where relevant guanaco (Lama guanicoe) bone assemblages were recovered. These sites record minimal anthropic involvement, basically cut marks on some guanaco bones accompanied by few stone tools, that we interpret as evidence for access and use of water logged immobilized or recently dead animals. Archaeological evidence for the use of these scavenging strategies is difficult to obtain at large archaeological sites that usually result from multiple occupations, since the distinction between the acquisition of actively pursued versus opportunistic animal resources is not straightforward. One conclusion from our review is that the best places to find and recognize this evidence are archaeological sites resulting from ephemeral occupations. The inclusion of these sites gives us access to crucial and rarely documented evidence for the long-term survival of hunter-gatherers.

Sepsis-Induced Immunosuppression.

Sepsis is expected to have a substantial impact on public health and cost as its prevalence increases. Factors contributing to increased prevalence include a progressively aging population, advances in the use of immunomodulatory agents to treat a rising number of diseases, and immune-suppressing therapies in organ transplant recipients and cancer patients. It is now recognized that sepsis is associated with profound and sustained immunosuppression, which has been implicated as a predisposing factor in the increased susceptibility of patients to secondary infections and mortality. In this review, we discuss mechanisms of sepsis-induced immunosuppression and biomarkers that identify a state of impaired immunity. We also highlight immune-enhancing strategies that have been evaluated in patients with sepsis, as well as therapeutics under current investigation. Finally, we describe future challenges and the need for a new treatment paradigm, integrating predictive enrichment with patient factors that may guide the future selection of tailored immunotherapy.

Innate immune mechanisms promote human response to Acinetobacter baumannii infection.

Acinetobacter baumannii is an opportunistic Gram-negative bacterium representing one of the leading causes of ventilator-associated pneumonia. The development of pneumonia results from a complex interplay between pathogens and pulmonary innate mucosal immunity. Therefore, the knowledge of the host immune responses is pivotal for the development of effective therapeutics to treat A. baumannii infections. Previous studies were conducted using cell lines and animal models, but a comprehensive understanding of the interaction between A. baumannii and primary human immune cells is still lacking. To bridge this gap, we investigated the response of primary monocytes, macrophages, and dendritic cells to the A. baumannii-type strain and an epidemic clinical isolate. We found that all immune cells trigger different responses when interacting with A. baumannii. In particular, macrophages and monocytes mediate bacterial clearance, whereas monocytes and dendritic cells activate a late response through the production of cytokines, chemokines, and the expression of co-stimulatory molecules. The epidemic strain induces lower expression of interleukin-10 and CD80 compared with the type strain, potentially constituting two immune evasion strategies.

A prospective evaluation of the diagnostic accuracy of the point-of-care VISITECT CD4 Advanced Disease test in seven countries.

BACKGROUND: CD4 measurement is pivotal in the management of advanced HIV disease. VISITECT® CD4 Advanced Disease (AccuBio Limited, Alva, UK; VISITECT) is an instrument-free, point-of-care, semi-quantitative test allowing visual identification of a CD4 ≤200 cells/µl, or >200 cells/µl from finger-prick or venous blood. METHODS: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM (clinicaltrials.gov: NCT04089423), people living with HIV of ≥18 years old were prospectively recruited in seven countries from outpatient departments if a tuberculosis symptom was present, and from inpatient departments. Participants provided venous blood for CD4 measurement using flow cytometry (reference standard) and finger-prick blood for VISITECT (index text), performed at point-of-care. Sensitivity, specificity, and positive and negative predictive values of VISITECT to determine a CD4 ≤200 cells/µl were evaluated. RESULTS: Among 1604 participants, the median flow cytometry CD4 was 367 (IQR 128-626) cells/µl and 521 (32.5%) had a CD4 ≤200 cells/µl. VISITECT sensitivity was 92.7% (483/521, 95% CI 90.1-94.7%) and specificity was 61.4% (665/1083, 95% CI 58.4-64.3%). For participants with a CD4 between 0-100, 101-200, 201-300, 301-500, and >500 cells/µl, VISITECT misclassified 4.5% (95% CI 2.5-7.2%), 12.5 (95% CI 8.0-18.2%), 74.1% (95% CI 67.0-80.5%), 48.0% (95% CI 42.5-53.6%), and 22.6% (95% CI 19.3-26.3%), respectively. CONCLUSIONS: VISITECT's sensitivity, but not specificity, met the World Health Organization's minimal sensitivity and specificity threshold of 80% for point-of-care CD4 tests. VISITECT's quality needs to be assessed and its accuracy optimized. VISITECT´s utility as CD4 triage test should be investigated.

Unintended Consequences: Risk of Opportunistic Infections Associated With Long-term Glucocorticoid Therapies in Adults.

Glucocorticoids are widespread anti-inflammatory medications used in medical practice. The immunosuppressive effects of systemic glucocorticoids and increased susceptibility to infections are widely appreciated. However, the dose-dependent model frequently used may not accurately predict the risk of infection in all patients treated with long-term glucocorticoids. In this review, we examine the risks of opportunistic infections (OIs) in patients requiring glucocorticoid therapy by evaluating the influence of the glucocorticoid dose, duration, and potency, combined with biological and host clinical factors and concomitant immunosuppressive therapy. We propose strategies to prevent OIs, which involve screening, antimicrobial prophylaxis, and immunizations. While this review focuses on patients with autoimmune, inflammatory, or neoplastic diseases, the potential risks and preventative strategies are likely applicable to other populations. Clinicians should actively assess the benefit-harm ratios of systemic glucocorticoids and implement preventive efforts to decrease their associated infections complications.

National Hospitalization Rates and In-Hospital Mortality Rates of HIV-Related Opportunistic Infections in the United States, 2011-2018.

BACKGROUND: Human immunodeficiency virus (HIV)-related opportunistic infections (OIs) cause substantial morbidity and mortality among people with HIV (PWH). US hospitalization and in-hospital mortality rates associated with OIs have not been published using data from the past decade. METHODS: We analyzed the National Inpatient Sample for the years 2011 through 2018. We used sociodemographic, financial, and hospital-level variables and identified hospitalizations for PWH and OI diagnoses. Using survey-weighted methods, we estimated all OI-related US hospitalization rates and in-hospital mortality per 100 000 PWH and modeled associated factors using survey-based multivariable logistic regression techniques. RESULTS: From 2011 to 2018, there were an estimated 1 710 164 (95% confidence interval [CI], 1 659 566-1 760 762) hospital discharges for PWH with 154 430 (95% CI, 148 669-159 717 [9.2%]) associated with an OI, of which 9336 (95% CI, 8813-9857; 6.0%) resulted in in-hospital mortality. Variables associated with higher odds of OI-related hospitalizations (compared to without an OI) included younger age, male sex, non-White race/ethnicity, and being uninsured (all likelihood ratio [LR] P < .001). Higher OI-related mortality was associated with older age (LR P < .001), male sex (LR P = .001), Hispanic race/ethnicity (LR P < .001), and being uninsured (LR P = .009). The OI-related hospitalization rate fell from 2725.3 (95% CI, 2266.9-3183.7) per 100 000 PWH in 2011 to 1647.3 (95% CI, 1492.5-1802.1) in 2018 (P < .001), but the proportion of hospitalizations with mortality was stable (5.9% in 2011 and 2018). CONCLUSIONS: Our findings indicate an ongoing need for continued funding of HIV testing, health insurance for all PWH, OI screening initiatives, review of current prophylaxis guidelines, and recruitment of more HIV clinicians.

Tracking Cryptococcal Meningitis to Monitor HIV Program Success During the Treat All Era: An Analysis of National Data in Botswana.

BACKGROUND: Cryptococcal meningitis (CM) causes substantial mortality in African countries with a high prevalence of human immunodeficiency virus (HIV), despite advances in disease management and increasing antiretroviral therapy (ART) coverage. Reliable diagnosis of CM is cheap and more accessible than other indicators of advanced HIV disease burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring CM incidence has the potential to serve as a valuable metric of HIV programmatic success. METHODS: Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analyzed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. CM case frequency was enumerated using a case definition and incidence calculated using national census data. RESULTS: A total of 1744 episodes of CM were identified; incidence declined from 15.0 (95% confidence interval [CI], 13.4-16.7) cases/100 000 person-years in 2015 to 7.4 (95% CI, 6.4-8.6) cases/100 000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44 years. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. CONCLUSIONS: CM incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test, highlighting the potential of using CM as key metric of program success in the Treat All era.

Efficacy of Bortezomib for Treating Anti-Interferon-Gamma Autoantibody-Associated Adult-Onset Immunodeficiency Syndrome.

BACKGROUND: Currently, there is no effective treatment for adult-onset immunodeficiency (AOID) syndrome with anti-interferon-gamma autoantibodies (anti-IFN-γ-auto-Abs). This study aimed to investigate the effectiveness of bortezomib (BTZ) for decreasing anti-IFN-γ-auto-Abs. METHODS: A pre- and post-intervention study was conducted from February 2017 through June 2019 at Siriraj Hospital (Bangkok, Thailand). Five patients were invited to receive once-weekly BTZ (1.3 mg/m2 body surface area) subcutaneously for 8 weeks followed by oral cyclophosphamide (1 mg/kg/d) for 4 months. The primary outcomes were the difference in antibody level at 8 and 48 weeks compared with baseline and the incidence of serious adverse events (AEs). The secondary outcome was the occurrence of opportunistic infections (OIs) during the 72 weeks after starting BTZ. RESULTS: The median patient age was 46 years (range, 34-53). All patients had 3-5 OIs prior to enrollment. All patients were receiving antimycobacterial agents for treatment of nontuberculous mycobacterial infection at enrollment. There was no significant difference in the mean optical density of auto-Abs at 8 weeks (3.73 ± 0.72) or 48 weeks (3.74 ± 0.53) compared with baseline (3.84 ± 0.49; P = .336 and P = .555, respectively). However, after serum dilution, the antibody titer nonsignificantly decreased 8-16 weeks after BTZ initiation (P = .345). Ten OIs were observed 24-72 weeks after BTZ initiation. CONCLUSIONS: Treatment with BTZ followed by cyclophosphamide yielded no significant decrease in antibody titer levels, and 10 OIs were observed during 24-72 weeks of BTZ treatment. No serious AEs were observed. Combining rituximab with BTZ is likely necessary to prevent generation of new autoantibody-producing plasma cells. Clinical Trials Registration. NCT03103555.

Chlorine Inactivation of Elizabethkingia spp. in Water.

We performed chlorine inactivation experiments for Elizabethkingia anophelis and E. meningoseptica bacterial strains from clinical and environmental sources. Free chlorine concentration × contact time values <0.04 mg·min/L achieved 99.9% inactivation of Elizabethkingia species, indicating chlorine susceptibility. Measures to control biofilm producing pathogens in plumbing are needed to prevent Elizabethkingia bacterial infections.

Impact of organized and opportunistic screening on excess mortality and on social inequalities in breast cancer survival.

In most developed countries, both organized screening (OrgS) and opportunistic screening (OppS) coexist. The literature has extensively covered the impact of organized screening on women's survival after breast cancer. However, the impact of opportunistic screening has been less frequently described due to the challenge of identifying the target population. The aim of this study was to describe the net survival and excess mortality hazard (EMH) in each screening group (OrgS, OppS, or No screening) and to determine whether there is an identical social gradient in each groups. Three data sources (cancer registry, screening coordination centers, and National Health Data System [NHDS]) were used to identify the three screening groups. The European Deprivation Index (EDI) defined the level of deprivation. We modeled excess breast cancer mortality hazard and net survival using penalized flexible models. We observed a higher EMH for "No screening" women compared with the other two groups, regardless of level of deprivation and age at diagnosis. A social gradient appeared for each group at different follow-up times and particularly between 2 and 3 years of follow-up for "OrgS" and "OppS" women. Net survival was higher for "OrgS" women than "OppS" women, especially for the oldest women, and regardless of the deprivation level. This study provides new evidence of the impact of OrgS on net survival and excess mortality hazard after breast cancer, compared with opportunistic screening or no screening, and tends to show that OrgS attenuates the social gradient effect.

Association of plasma NRP2 and VEGF-C levels with prostate cancer disease severity.

BACKGROUND: Neuropilin 2 (NRP2) expression in tissue is an independent prognostic factor for aggressive prostate cancer. Since the NRP2 pathway activation is thought to occur in part through secondary resistance, quantification of NRP2 in initial tissue biopsy specimens collected at diagnosis may have limited utility in identifying patients at highest risk for morbidity and mortality. Given that metastatic tissue is only occasionally obtained for analysis, there is a need for development of a plasma biomarker indicative of NRP2 pathway activation to potentially inform prostate cancer prognosis. Therefore, we investigated if plasma levels of NRP2 or vascular endothelial growth factor C (VEGF-C), a known soluble ligand of NRP2, are prognostic for prostate cancer. We hypothesized that plasma NRP2 and VEGF-C would be associated with more advanced disease or relapsed disease. METHODS: NRP2 and VEGF-C levels were quantified by enzyme-linked immunoassay in plasma samples obtained from 145 prostate cancer patients in an opportunistic biobank. These patients were either (1) newly diagnosed (N = 28), (2) in remission (N = 56), or (3) relapsed disease (N = 61). Plasma samples from 15 adult males without known malignancy served as a comparator cohort. Statistical analysis was performed to investigate the association of plasma NRP2/VEGF-C with patient outcomes, adjusting for age, race, prostate-specific antigen (PSA), Gleason score, and tumor stage at diagnosis. RESULTS: Neither NRP2 nor VEGF-C levels were significantly different in cancer patients compared to noncancer controls. We observed no clear association between plasma NRP2 and disease severity. Increased plasma VEGF-C was significantly associated with disease remission and correlated with Stage I/II and intermediate-risk Gleason score. Neither NRP2 nor VEGF-C correlated with PSA level. CONCLUSIONS: Although tissue NRP2 expression correlates with severe disease, this was not observed for plasma NRP2. Plasma NRP2 levels did not correlate with disease severity or relapse. VEGF-C was highest in patients in remission and with less severe disease. Future investigation is needed to identify noninvasive methods to assess tumor NRP2 status.

A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections.

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

Utilization of opportunistic cervical cancer screening in Nigeria.

BACKGROUND: While various interventions have been conducted to decrease cervical cancer's burden in Nigeria, no study has examined the trends in cervical cancer screening uptake over time. The present study sought to fill this gap in knowledge using data collected at Jos University Teaching Hospital (JUTH) in Nigeria. METHODS: Data collected continuously between 2006 and 2016 were analyzed to identify trends in screening uptake, changes in risk factors for cervical cancer, and to identify factors for women screened at Jos University Teaching Hospital (JUTH) in Jos, Nigeria. Categorical analyses and logistic regression models were used to describe patient characteristics by year, and to identify factors associated with repeated screening uptake. RESULTS: A total of 14,088 women who were screened between 2006 and 2016 were included in the database; 2,800 women had more than one screening visit. Overall, screening uptake differed significantly by year. On average women were first screened at age 38. About 2% of women screened were women living with HIV. Most women (86%) had normal pap smear at first screening, with the greatest decreased risk of abnormalities observed between 2011 and 2014. Odds of a follow-up screening after a normal result decreased significantly between 2008 and 2016 compared to women screened in 2006 and 2007. Finally, women living with HIV had increased odds of follow-up screening after having a normal pap smear. CONCLUSIONS: These findings contribute to our understanding of the potential social and health system barriers to cervical cancer control in Nigeria. The findings may assist policy makers to design interventions to increase access and compliance to recommended screening schedules in this vulnerable population.

Survival after cryptococcosis in Germany: A retrospective multicenter cohort study of patients diagnosed between 2004 and 2021.

Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome. We included 64 patients with underlying HIV infection (55%) or other predispositions. Molecular typing by MLST documented 20 individual sequence types among 42 typed isolates. A fatal outcome was documented in 14% of patients in the first two months after diagnosis.

Source-to-tap investigation of the occurrence of nontuberculous mycobacteria in a full-scale chloraminated drinking water system.

Nontuberculous mycobacteria (NTM) in drinking water are a significant public health concern. However, an incomplete understanding of the factors that influence the occurrence of NTM in drinking water limits our ability to characterize risk and prevent infection. This study sought to evaluate the influence of season and water treatment, distribution, and stagnation on NTM in drinking water. Samples were collected source-to-tap in a full-scale, chloraminated drinking water system approximately monthly from December 2019 to November 2020. NTM were characterized using culture-dependent (plate culture with matrix-assisted laser desorption ionization-time-of-flight mass spectrometry [MALDI-TOF MS] isolate analysis) and culture-independent methods (quantitative PCR and genome-resolved metagenomics). Sampling locations included source waters, three locations within the treatment plant, and five buildings receiving water from the distribution system. Building plumbing samples consisted of first draw, 5-min flush, and full flush cold-water samples. As the study took place during the COVID-19 pandemic, the influence of reduced water usage in three of the five buildings was also investigated. The highest NTM densities source-to-tap were found in the summer first draw building water samples (107 gene copies/L), which also had the lowest monochloramine concentrations. Flushing was found to be effective for reducing NTM and restoring disinfectant residuals, though flush times necessary to improve water quality varied by building. Clinically relevant NTM species, including Mycobacterium avium, were recovered via plate culture, with increased occurrence observed in buildings with higher water age. Four of five NTM metagenome-assembled genomes were identified to the species level and matched identified isolates.IMPORTANCENTM infections are increasing in prevalence, difficult to treat, and associated with high morbidity and mortality rates. Our lack of understanding of the factors that influence NTM occurrence in drinking water limits our ability to prevent infections, accurately characterize risk, and focus remediation efforts. In this study, we comprehensively evaluated NTM in a full-scale drinking water system, showing that various steps in treatment and distribution influence NTM presence. Stagnant building water contained the highest NTM densities source-to-tap and was associated with low disinfectant residuals. We illustrated the differences in NTM detection and characterization obtained from culture-based and culture-independent methods, highlighting the complementarity between these approaches. We demonstrated that focusing NTM mitigation efforts in building plumbing systems, which have the highest NTM densities source-to-tap, has potential for immediate positive effects. We also identified steps during treatment that increase NTM levels, which provides beneficial information for utilities seeking to reduce NTM in finished water.

Cytomegalovirus infection among people living with HIV in Sweden: Case profiles, treatment strategies and patient outcomes at Karolinska University Hospital 2010-2020.

OBJECTIVES: In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described. METHODS: Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020. RESULTS: We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/µL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection. CONCLUSIONS: Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications.

Periprosthetic fractures are osteoporotic fractures: missed opportunities for osteoporosis diagnosis.

Joint replacement surgery is common in older adults, leading to increasing periprosthetic fracture (PPFx) occurrence. We reviewed all PPFx seen over a 4-year period at an academic hospital. Clinical osteoporosis could be diagnosed based on existing data in 104 (67%) at the time of PPFx. Periprosthetic fractures are generally osteoporosis-related. PURPOSE: Periprosthetic fractures (PPFx) cause morbidity, mortality, and cost. This study's purpose was to describe osteoporosis-related data available at the time of PPFx. METHODS: The electronic medical record (EMR) of PPFx patients seen over 4 years in a university orthopedic practice were reviewed. Demographic data and osteoporosis relevant parameters were collected. Prior DXA studies were reviewed, and L1 Hounsfield unit (HU) measurements were performed on CT scans obtained within 2 years before PPFx. Clinical osteoporosis was defined as prior diagnosis, prescribed osteoporosis treatment, T-score ≤ - 2.5, HU ≤ 100, or prior fracture. RESULTS: Records of 156 PPFx patients (115 F/41 M), mean (SD) age 75.4 (11.9), were reviewed. Almost all 153/156 (98%) of these fractures were femoral. Falls caused 139 (89%); 12 (8%) were spontaneous. Mean time post-arthroplasty was 7.9 (6.3) years. Prior fragility fracture(s) occurred in 72 (46%); 14 were PPFx. Osteoporosis was previously diagnosed in 45 (29%) and medications prescribed in 41 (26%). Prior to PPFx, DXA data were available in 62, mean (SD) lowest T-score was - 1.9 (0.9) and was ≤ - 2.5 in 19. CT data were available in 46; mean (SD) L1 HU was 79.0 (29.4) and was ≤ 100 in 35. Based on existing data, clinical osteoporosis could have been diagnosed in 104 (67%) at the time of PPFx. CONCLUSION: Periprosthetic fractures are osteoporosis-related. They occur in older adults, often female, and result from falls; BMD, when assessed, is low. Data available at the time of PPFx often allows osteoporosis diagnosis; this should prompt evaluation and pharmacologic treatment consideration.

Artificial intelligence-enhanced opportunistic screening of osteoporosis in CT scan: a scoping Review.

PURPOSE: This scoping review aimed to assess the current research on artificial intelligence (AI)--enhanced opportunistic screening approaches for stratifying osteoporosis and osteopenia risk by evaluating vertebral trabecular bone structure in CT scans. METHODS: PubMed, Scopus, and Web of Science databases were systematically searched for studies published between 2018 and December 2023. Inclusion criteria encompassed articles focusing on AI techniques for classifying osteoporosis/osteopenia or determining bone mineral density using CT scans of vertebral bodies. Data extraction included study characteristics, methodologies, and key findings. RESULTS: Fourteen studies met the inclusion criteria. Three main approaches were identified: fully automated deep learning solutions, hybrid approaches combining deep learning and conventional machine learning, and non-automated solutions using manual segmentation followed by AI analysis. Studies demonstrated high accuracy in bone mineral density prediction (86-96%) and classification of normal versus osteoporotic subjects (AUC 0.927-0.984). However, significant heterogeneity was observed in methodologies, workflows, and ground truth selection. CONCLUSIONS: The review highlights AI's promising potential in enhancing opportunistic screening for osteoporosis using CT scans. While the field is still in its early stages, with most solutions at the proof-of-concept phase, the evidence supports increased efforts to incorporate AI into radiologic workflows. Addressing knowledge gaps, such as standardizing benchmarks and increasing external validation, will be crucial for advancing the clinical application of these AI-enhanced screening methods. Integration of such technologies could lead to improved early detection of osteoporotic conditions at a low economic cost.