Increased Risk Of Infection Research Articles

The role of species ecology in predicting Toxoplasma gondii prevalence in wild and domesticated mammals globally.

Macroecological approaches can provide valuable insight into the epidemiology of globally distributed, multi-host pathogens. Toxoplasma gondii is a protozoan that infects any warm-blooded animal, including humans, in almost every habitat worldwide. Toxoplasma gondii infects its hosts through oocysts in the environment, carnivory of tissue cysts within intermediate host prey and vertical transmission. These routes of infection enable specific predictions regarding the ecological and life history traits that should predispose specific taxa to higher exposure and, thus infection rates of T. gondii. Using T. gondii prevalence data compiled from 485 studies representing 533 free-ranging wild mammalian species, we examined how ecological (habitat type, trophic level) and life history (longevity, vagility, gestation duration and torpor) traits influence T. gondii infection globally. We also compared T. gondii prevalence between wild and domesticated species from the same taxonomic families using data compiled from 540 studies of domestic cattle, sheep, and pigs. Across free-ranging wildlife, we found the average T. gondii prevalence was 22%, which is comparable to the global human estimate. Among ecological guilds, terrestrial species had lower T. gondii prevalence than aquatic species, with freshwater aquatic taxa having an increased prevalence compared to marine aquatic species. Dietary niches were also influential, with carnivores having an increased risk compared to other trophic feeding groups that have reduced tissue cyst exposure in their diet. With respect to influential life history traits, we found that more vagile wildlife species had higher T. gondii infection rates, perhaps because of the higher cumulative risk of infection during movement through areas with varying T. gondii environmental loads. Domestic farmed species had a higher T. gondii prevalence compared to free-ranging confamilial wildlife species. Through a macroecological approach, we determined the relative significance of transmission routes of a generalist pathogen, demonstrating an increased infection risk for aquatic and carnivorous species and highlighting the importance of preventing pathogen pollution into aquatic environments. Toxoplasma gondii is increasingly understood to be primarily an anthropogenically-associated pathogen whose dissemination is enhanced by ecosystem degradation and human subsidisation of free-roaming domestic cats. Adopting an ecosystem restoration approach to reduce one of the world's most common parasites would synergistically contribute to other initiatives in conservation, feline and wildlife welfare, climate change, food security and public health.

A case-control study of the infection risk of H5N8 highly pathogenic avian influenza in Japan during the winter of 2020–2021

In Japan, outbreaks of H5N8 highly pathogenic avian influenza (HPAI) were reported between November 2020 and March 2021 in 52 poultry farms. Understanding HPAI epidemiology would help poultry industries improve their awareness of the disease and enhance the immediate implementation of biosecurity measures. This study was a simulation-based matched case-control study to elucidate the risk factors associated with HPAI outbreaks in chicken farms in Japan. Data were collected from 42 HPAI-affected farms and 463 control farms that were within a 5-km radius of each case farm but remained uninfected. When infected farms were detected as clusters, one farm was randomly selected from each cluster, considering the possibility that the cluster was formed by farm-to-farm transmission within an epidemic area. For each case farm, up to three control farms were selected within a 5-km radius. Overall, 26 case farms (16 layer and 10 broiler farms) and 75 control farms (45 layer and 30 broiler farms) were resampled 1000 times for the conditional logistic regression model with explanatory variables comprising geographical factors and farm flock size. A larger flock size and shorter distance to water bodies from the farm were found to increase infection risk in layer farms. Similarly, in broiler farms, a shorter distance to water bodies increased infection risk. On larger farms, frequent access of farm staff and instrument carriages to premises could lead to increased infection risk. Waterfowl visiting water bodies around farms may also be associated with infection risk.

Enhanced antimicrobial efficacy of chlorhexidine-encapsulated halloysite nanotubes incorporated in presurgical orthopedic appliances: an in vitro, controlled study.

Presurgical infant's orthopedic appliances (PSIOs) play an increasingly crucial role in the interdisciplinary management of neonatal CLP, aiming to improve and maintain adequate nasolabial aesthetics, followed by primary lip/nasal surgery in both unilateral and bilateral CLP cases. The use of PSIOs in cleft lip and palate patients can lead to contamination with oral microflora, acting as a potential reservoir for infectious microorganisms. Acrylic surfaces might provide retention niches for microorganisms to adhere, and inhabit, which is difficult to control in immunocompromised patients, thus predisposing them to increased infection risks. The objective of this multi-assay in vitro study was to investigate the effects of incorporating chlorhexidine-loaded halloysite nanotubes (CHX-HNTs) fillers on the morphological, cytotoxic, release, and antimicrobial characteristics of self-cured acrylic polymethyl methacrylate (PMMA) material used in pre-surgical orthopedic appliances. Disk-shaped PMMA specimens were prepared with varying proportions of CHX-HNTs. A control group without any addition served as a reference, and four experimental samples contained a range of different concentrations of CHX-HNTs (1.0, 1.5, 3, and 4.5 wt%). The antimicrobial efficacy was assessed using an agar diffusion test against common reference microorganisms: Candida albicans, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus agalactiae. Cytotoxicity was examined using the L929 cell line (mouse fibroblasts) through a (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, MTT) cell viability assay. The release kinetics of CHX were monitored using UV-spectral measurements. The statistical analysis used a one-way ANOVA followed by Tukey's post hoc test. The integration of CHX-HNTs in PMMA exhibited a substantial dose-dependent antifungal and antibacterial effect against microorganisms at tested mass fractions (1.0 to 4.5 wt%). CHX release was sustained for up to 60 days, supporting prolonged antimicrobial activity. Furthermore, no significant cytotoxicity was determined in the L929 fibroblast cell line (control), indicating the biocompatibility of the CHX-HNTs-enhanced PMMA. Incorporating CHX-HNTs in PMMA successfully enhanced its antimicrobial properties, providing sustained CHX release and superior antimicrobial efficacy. These findings demonstrate the potential of antimicrobial nanoparticles in dental therapies to improve therapeutic outcomes. However, rigorous further clinical trials and observational studies are warranted to validate the practical application, safety, and efficacy. This study has the potential to make a major impact on the health of infants born with cleft lip and palate by helping to reduce the prevalence of infectious illnesses. The incorporation of CHX-HNTs into PMMA-based appliances is a novel promising preventive approach to reduce microbial infections.

Frequency of Peripheral IV Catheter in Neonates with Prolong Stay in Emergency of Low-Income Country

BACKGROUND Peripheral intra venous catheter-the usual route for administrating iv antibiotics, nutrition, and other medications. It is secured by splints and adhesive dressings to the skin. However, prolong stay in the ED, and other factors result in frequent IV cannulation which increases the risk of infection and is always a painful procedure. Multiple dressings used to secure the cannula may also result in skin injury and further increase risk for infection. OBJECTIVE The present study aims to establish a relationship between length of stay of neonates and the number of peripheral IV catheter lines placed. MATERIAL AND METHOD This is a retrospective chart review of neonates admitted through the emergency room of a public sector hospital supported by Child life foundation, their length of stay, and the number of IV catheters used during their stay with the help of EMR data from doctors, staff, and pharmacists for each patient. RESULTS 1641 neonates admitted in ED between JAN-JUN 2023. 827(50.3%) neonates stayed in ED for less than 12 hours, with 1.7 average IV cannulations per neonate. 463(28.2%) neonates with length of stay between 12–24 hours had 2.08 IV cannulations per neonate. 239(14.56%) neonates stayed for 24–48 hours, with 2.3 IV cannulations per neonate. 78 (4.75%) neonates with length of stay between 48–72 had 2.76 IV cannulations per neonate. 34(2.07%) neonates stayed for more than 72hrs, with 3.17 IV cannulations per neonate. We established that as the need for IV medication and nutrition prolongs, so does the frequency of IV cannulations at new sites. The neonates were discharged on IV medication for a further 3–6 days, hence further increasing the need and number of peripheral IV cannulations per neonate. The frequency of change in cannulations is more in pre term as compared to term babies. CONCLUSION Increase length of stay is directly related to increase frequency of change in IV cannulation. Umbilical vein and peripherally inserted central catheter (PICC) can be utilized for IV antibiotics, nutrition, and other medications in ED. This will help in decreasing the risk of infection and painful stimulus to the neonates.

Meta-analysis of postoperative incision infection risk factors in colorectal cancer surgery.

To evaluate the risk factors for postoperative incision infection in colorectal cancer, this meta-analysis aimed to identify key variables impacting infection incidence following colorectal cancer surgery. Utilizing a meta-analytical approach, studies published from January 2015 to December 2022 were systematically collected and analyzed through the assessment of factors like body mass index, diabetes, albumin levels, malnutrition, and surgical duration. The meta-analysis of eleven high-quality studies revealed that elevated BMI, diabetes, low albumin levels, malnutrition, and extended surgical duration were associated with increased infection risk, while laparoscopic procedures showed potential for risk reduction. This study underscores the significance of preoperative risk assessment and management in mitigating postoperative incision infections in colorectal cancer patients. The findings present actionable insights for clinicians to enhance patient prognoses and overall quality of life.

Efficacy of Plasma Rich in Growth Factors for Healing Chronic Skin Ulcers: A Systematic Review of Randomized Controlled Trials With Meta-Analysis

Background. Chronic skin ulceration is a serious pathological condition for which the adjuvant use of platelet-rich plasma (PRP) has been indicated. However, evidence for the use of PRP in patients with chronic skin ulcers remains insufficient due to a large heterogeneity in experimental designs, PRP composition, and preparation protocols. Objective. To assess previously published reports of the clinical effect of plasma rich in growth factors (PRGF) on chronic skin wounds. Methods. A comprehensive search of the PubMed, Cochrane Library, and Scopus databases was performed to identify randomized controlled trials (RCTs) assessing the effect of PRGF on chronic ulcer healing, with no limitation regarding publication date (up to September 1, 2022). Percentage area reduction and probability of complete healing in chronic ulcers, pain reduction, infection risk, and cost savings were analyzed. A meta-analysis was performed, and the overall evidence was qualified using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results. A total of 113 studies were identified. After full-text screening, 5 RCTs met the inclusion criteria. The meta-analysis showed a significant effect of PRGF on both wound area reduction (mean difference, 56.90% [95% CI, 52.28-61.51], I² = 0%; P = .56) and on the probability of complete healing (RR, 7.07 [95% CI, 1.84-27.16], I² = 0%; P = .53) in chronic ulcers. The overall risk of bias rating was “some concerns,” whereas the certainty of evidence was high for both outcomes. A qualitative analysis suggested that PRGF did not increase infection risk and was able to reduce wound pain. Conclusion. The use of PRGF significantly enhances wound area reduction and also the probability of complete healing in chronic ulcers. More studies are needed to assess the effect of PRGF on pain and infection, as well as its cost-effectiveness.

A comprehensive study on the risk factors and pathogen analysis of postoperative wound infections following caesarean section procedures.

Postoperative wound infections (PWIs), a subtype of surgical site infections, are a significant concern for patients undergoing caesarean sections (C-sections). Understanding risk factors and pathogen profiles can greatly assist in early diagnosis and effective treatment. This study aimed to identify risk factors and analyse the pathogenic landscape contributing to PWIs in C-sections. A nested case-control study was carried out, utilising stringent criteria for case selection and control matching. Diagnostic criteria for surgical site infections included both clinical and microbiological parameters. Risk variables examined included patient age, Body Mass Index, duration of surgery and several other clinical indicators. Microbiological analysis was performed using the BD Phoenix-100 Automated Bacterial Identification System. Statistical analyses were conducted using SPSS version 26.0, and risk factors were evaluated through both univariate and multivariate analyses. A total of 50 patients, aged between 20 and 45 years (mean age 26.3 ± 5.6), developed PWIs following C-sections. The study revealed a temporal distribution and various clinical indicators of PWIs, including elevated white blood cell count and C-reactive protein levels. Gram-negative bacteria were found to be more prevalent at 57.4%. Notable pathogens included Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrobial resistance patterns were also identified, highlighting the need for a targeted antibiotic approach. Increased infection risks were linked to lack of prophylactic antibiotics, absence of preoperative povidone-iodine antisepsis, operations over an hour, anaemia, amniotic fluid contamination, diabetes, GTI, premature rupture of membranes and white blood cells counts above 10 × 109 /L. The study provides critical insights into the risk factors and microbial agents contributing to PWIs following C-sections. Our findings emphasise the importance of early diagnosis through clinical and laboratory parameters, as well as the need for constant surveillance and reassessment of antibiotic stewardship programs.

Cutaneous adaptive immunity and uraemia: a narrative review.

Chronic kidney disease affects 1 in 10 people globally, with a prevalence twenty times that of cancer. A subset of individuals will progress to end-stage renal disease (ESRD) where renal replacement therapy is required to maintain health. Cutaneous disease, including xerosis and pruritus, are endemic amongst patients with ESRD. In the uraemia-associated immune deficiency of ESRD, impaired circulating immune responses contribute to increased infection risk and poorer vaccination response. Clinical manifestations of dysregulated adaptive immunity within the skin have been well-described and have been posited to play a role in cutaneous features of ESRD. However, our understanding of the mechanisms by which adaptive immunity within the skin is affected by uraemia is relatively limited. We provide an overview of how the cutaneous adaptive immune system is impacted both directly and indirectly by uraemia, highlighting that much work has been extrapolated from the circulating immune system and often has not been directly evaluated in the skin compartment. We identify knowledge gaps which may be addressed by future research. Ultimately, greater understanding of these pathways may facilitate novel therapeutic approaches to ameliorate widespread cutaneous symptomatology in ESRD.

Widespread circulation and transmission risk of Mycobacterium avium subsp. paratuberculosis at the livestock-wildlife-environment interface in a Mediterranean agro-forestry farmstead

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic infection affecting ruminants and other species worldwide. Information on the ecological factors that increase infection risk at the livestock-wildlife-environment interface remains scarce. Thus, this work aimed at determining which factors modulate the exposure of a mammal community within a Mediterranean agro-forestry farmstead to MAP. Through field, molecular and ecological modeling approaches, MAP prevalence, distribution and spatial risk at the livestock-wildlife-environment was estimated in the study area by screening 436 samples (cattle, n = 150; wildlife, n = 206; soil, n = 80). Using molecular detection of IS900 as proxy, MAP was identified in ten wild mammal species. Being a central prey of mesocarnivores in Portugal, the high prevalence of MAP in the wild rabbit (19%) may be related with red fox's (22%). MAP was also detected in cattle managed in the farmstead (animal and herd prevalence, 54% and 100%) and in soil (44%), which may perpetuate intraspecies and interspecies transmission. Wildlife diversity showed a positive influence on MAP presence in wild mammals, while wildlife abundance showed a negative effect. Land use variables exerted distinct degrees of impact upon MAP detection in specific groups of mammals: mixed forest cover showed positive influence on carnivores, and shrubland showed positive effect on wild rabbits. The prevalence of MAP in cattle showed a negative influence on the detection of MAP in lagomorph, which may stem from wild rabbit lower density and avoidance of cattle areas. Based on explanatory variables, the spatial prediction of MAP occurrence in wildlife indicated two hotspots with increased exposure risk but future studies are needed to confirm this projection.This work represents the most comprehensive molecular survey of MAP occurrence and determinants in Mediterranean agroecosystems leveraging the principles and tools of community ecology, debating potential biological and ecological effects underlying MAP transmission.

Lowering Cranioplasty Infection Incidence with Novel Bone Flap Storage Protocol: A Retrospective Cohort Study

IntroductionAfter craniectomy, autologous bone flaps may be stored using wet or dry cryopreservation. After brain edema subsides, they are replaced during an operation termed “cranioplasty.” Cranioplasty is associated with 15% infection incidence. MethodsWe conducted a retrospective comparison of infection outcomes between “wet” and “dry” cryopreservation of cranioplasty bone flaps. Historically, bone flaps were stored utilizing “wet” cryopreservation – bone flap storage in 1 L of Lactated Ringer’s solution containing 80mg gentamicin and 2g nafcillin in a sterile plastic container secured in an unsterile plastic bag. Our newer dry cryopreservation protocol involved storage in gauze soaked in 80mg gentamicin and 2g nafcillin within a 3-layer sterile bag system. Results119 autologous bone flaps were included with median follow-up of 3.9 months from cranioplasty. Overall, 10.9% became infected requiring subsequent surgery. 18.4% of 49 bone flaps stored using wet cryopreservation became infected compared to only 5.7% of 70 dry cryopreservation bone flaps (p 0.038; Relative risk 0.311; Absolute risk reduction 12.7%). Tobacco use (p 0.076; RR 3.17) was not associated with increased infection risk. Infection incidence was similar for traumatic craniectomy indications compared to the other indications (12.0% trauma versus 10.1% other; p 0.750). On average, infected cranioplasty patients spent 8.5 more days hospitalized and faced increased risk of additional complications. ConclusionDry cryopreservation significantly decreases infection after cranioplasty when compared with wet cryopreservation, which mitigates additional morbidity, mortality, and costs attributable to cranioplasty infection. Other nonmodifiable risk factors for cranioplasty infection were identified.

Development of a Pipeline for Removing Allergy Labels in Patients Undergoing Hematopoietic Stem Cell Transplantation

Penicillin allergy is reported by 10-20 % of patients, but when evaluated only 1-2% may have a true allergy. Patients undergoing HSCT have a high likelihood of requiring beta-lactam antibiotics due to increased infection risk, which can be limited by a penicillin allergy label. When a penicillin allergy is recorded, alternatives are needed including more-expensive, broader-spectrum antibiotics, with increases in drug-resistant bacteria, longer hospital stays, higher expenditures, and increases in nosocomial infections such as C. difficile colitis. This group of patients already has extensive pre-treatment testing, and would particularly benefit from allergy de-labeling. This study aimed to develop a self-sustaining, low-cost pipeline between a HSCT clinic and an allergy clinic to identify and successfully de-label low-risk patients who endorse an allergy to penicillin, amoxicillin, amoxicillin-clavulanate, piperacillin-tazobactam, or ampicillin before admission to the hospital. We developed a survey to triage allergy risk, identified key stakeholders in building the pipeline, and underwent four plan, do, study, act (PDSA) cycles. Changes were made in each of the PDSA cycles to minimize cost and uncompensated provider time as well as increase patient retention throughout the pipeline by increasing appointment availability and decreasing reliance on patients to independently progress through the pathway. Of the 410 patients with planned HSCT who were screened over 11 months, we found that 89 (21.7%) patients were listed as having penicillin and/or beta lactam allergy. 98.5% (n=66/67) of participants completed the survey accurately when confirmed by an allergist, and the survey was 100% accurate in predicting de-labeling success in low-risk patients. Of eligible patients, 43.8% (n=39) were successfully de-labeled before their transplant date and 97.4% (n=38) have undergone HSCT to date. This pipeline is maintained by approximately 5 hours of work per week (1 hour of allergy physician time, 4 hours of nurse and/or clinical coordinator time) and no other direct costs. There is an estimated direct savings of at least $1,914.93 per patient de-labeled. We successfully designed and implemented a pipeline between the HSCT clinic and the allergy clinic as a quality improvement initiative to identify and address high rates of reported beta-lactam allergies. We identified and addressed patient-based factors, logistical, temporal, and financial barriers that impacted patient retention and sustainability. This model is expected to have significant and sustained cost-savings for the healthcare system as well as improve patient outcomes, and this hypothesis is currently undergoing formal analysis. We anticipate that this model can be used to create a similar pipeline in other healthcare systems for HSCT patients as well as other clinical settings such as oncology and CAR-T therapy.

Respiratory infection risk in primary Sjögren's syndrome complicated with interstitial lung disease: a retrospective study.

To explore clinical and laboratory characteristics of primary Sjögren's syndrome (pSS) complicated with interstitial lung disease (ILD) and investigate the risk factors for respiratory infections in pSS-ILD. A cohort of 162 pSS-ILD patients in Peking University People's Hospital from 2015 to 2020 were included, and all medical records were completely collected. We screened 53 patients suffering from respiratory infections as study cases, compared with 109 age- and sex-matched controls. Differences between infection group and control group were compared. Univariate and multivariate binary logistic regression tests were conducted to identify potential risk factors for respiratory infections in pSS-ILD patients. Among 162 pSS-ILD patients, 32.72% (53/162) suffered from respiratory infections. The most frequent type of ILD was nonspecific interstitial pneumonia (32.08%, 51/159), and the most common type of pathogen was bacteria (64.25%, 34/53). Infection group showed higher levels of ESSDAI (P < 0.001), CRP (P < 0.001), ESR (P = 0.003), and C3 (P = 0.020) but lower level of DLCO-SB (P = 0.015). Univariate logistic model revealed that PAH and the use of glucocorticoid increased infection risk in pSS-ILD patients. On multivariate logistic regression analysis, PAH (OR = 3.993, 95% CI = 1.192-13.373, P = 0.025) and severe reduction of DLCO (DLCO-SB < 40%, OR = 4.625, 95% CI = 1.281-16.702, P = 0.019) were significantly associated with increased risk of respiratory infections in pSS-ILD patients. Among pSS-ILD patients, the most frequent type of ILD was nonspecific interstitial pneumonia. In patients with infection, bacteria were the most common pathogen. Higher levels of ESSDAI, CRP, ESR, and C3 may be correlated with increased infection risk. PAH and reduction of DLCO were identifiedas independent risk factors. Key Points • ILD and infectious diseases severely affect pSS patient conditions. • Higher levels of ESSDAI, CRP, ESR, and C3 may be correlated with increased infection risks in pSS-ILD. • PAH and reduction of DLCO were identified as independent risk factors for lower respiratory infection.

Predicting peripartum infection in laboring patients at high risk in Cameroon, Africa

ObjectiveTo develop a predictive model for peripartum infection among high risk laboring patients in Cameroon, Africa. Study designWe conducted a secondary analysis of the Cameroon Antibiotic Prophylaxis Trial (NCT 3248297), a multicenter 3-arm double-blind randomized controlled trial of oral azithromycin ± amoxicillin among term pregnancies with prolonged labor or rupture of membranes in Cameroon 1/2018–5/2020. Patients with chorioamnionitis prior to randomization, study drug contraindications, or planned cesarean were excluded. The outcome of interest was a composite of maternal peripartum infection (chorioamnionitis, endometritis, sepsis by World Health Organization criteria, wound infection/abscess) diagnosed up to 6 weeks postpartum. Potential predictors were compared between patients with and without the composite outcome, and evaluated at a 0.05 alpha level. Statistically significant exposures were analyzed using multivariable regression (to generate adjusted odds ratios and 95 % confidence intervals) with backwards selection to generate a parsimonious model. Receiver operating characteristic curves with associated area under the curve assessed the model’s predictive ability. A nomogram based on the final best fit multivariable model was constructed. ResultsOf 756 patients in the parent trial, 652 were analyzed: 45 (7 %) had peripartum infection. Those with infection were more likely to be nulliparous, lower education level, higher gestational age, receive antibiotics per hospital protocols, and undergo cesarean. In our best-fit multivariable model, none/primary education (vs university), cesarean birth, and antibiotic receipt per physician discretion (vs for cesarean prophylaxis) were significantly associated with increased infection risk. This model was moderately predictive (AUC = 0.75, 95 % CI 0.67–0.82). When using this 3 factor model, for a patient with a cesarean birth, receipt of antibiotics per physician discretion, and university education, the probability of peripartum infection was 35 % (95 % CI 0.11–0.73). ConclusionsWhile several variables such as parity are associated with infectious morbidity within 6 weeks among high risk laboring patients in Cameroon, only education level, antibiotic indication, and cesarean birth were independently associated, and a model including these 3 factors was moderately predictive. Validation of our findings in a larger population is warranted.

Attenuated inflammatory response in infant mice with Staphylococcus epidermidis CNS catheter infection

Children under one year of age are consistently found to be at the highest risk for shunt infection as a complication of hydrocephalus treatment, and repeated infections in the same patient are common. The mechanisms responsible for the increase in infant infection are not known. Our laboratory adapted our existing mouse model of Staphylococcus epidermidis central nervous system (CNS) catheter infection to characterize infection in infant mice as a foundation of on-going studies to determine the mechanisms of increased morbidity in infant shunt infections. The well-established model of S. epidermidis biofilm infection in the CNS was adapted to generate infection in 14-day old C57BL/6 mice. The catheter preparation was identical to the adult model, in which silicone catheters are pre-coated with a clinically derived biofilm-forming strain of S. epidermidis strain 1457) to introduce S. epidermidis into the brain. The catheters are stereotactically implanted into the lateral left ventricle. Bacterial titers as well as cytokine and chemokine levels were measured at days 1, 3, and 5 in mice implanted with sterile and S. epidermidis-coated catheters. Cultures demonstrated both catheter-associated and parenchymal infection through day 5 post-implantation. In contrast to prior adult models of CNS catheter infection, however, the catheter-associated bacterial burdens were less than or equal to parenchymal bacterial burdens. There was no significant difference between the chemokine and cytokine levels in the brain tissues of pups with sterile versus S. epidermidis infected catheters for any of the analytes tested. The infant model of S. epidermidis CNS catheter infection is characterized by both a greater degree of parenchymal spread of bacteria and the absence of the elevated pro-inflammatory cytokines previously observed in adult mice with this infection. The attenuated inflammatory response may contribute to the increased infection risk observed in this population.

Nutrition, Immune Function, and Infectious Disease in Military Personnel: A Narrative Review.

Consuming a diet that meets energy demands and provides essential nutrients promotes a healthy immune system, while both under- and over-nutrition have been associated with immune dysfunction. Military personnel comprise a unique population who frequently endure multi-stressor environments, predisposing them to immune decrements. Additionally, 49% and 22% of active duty U.S. military personnel are classified as overweight and obese, respectively. A literature search on PubMed was conducted to identify studies, reports, review papers, and references within those sources relevant to the topic area. Military personnel experiencing either under- or over-nutrition can suffer from degraded health, readiness, and performance. Insufficient intake of nutrients during military operations increases infection risk and negatively impacts infection recovery. Energy, protein, iron, zinc, and vitamins C and D are nutritional areas of concern that may impact immune competence in a multi-stressor environment. Over-nutrition can promote accretion of excess body fat and obesity, which contributes to a chronic inflammatory state that coincides with immune impairments. Prioritizing efforts to optimize nutrient intake is one approach for reducing disease burden and improving readiness. This review discusses nutritional concerns concomitant to multi-stressor environments that impact immune function, and the relevance of obesity to infectious disease risk in the military population.

Treatment Outcomes and Prognostic Factors with Lenalidomide, Bortezomib, and Dexamethasone (RVd) Alone Versus Rvd Plus Autologous Stem Cell Transplantation (ASCT) in African American (AA) Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) in the Determination Phase 3 Trial

Background AA pts with NDMM have equal or longer overall survival (OS) vs White pts when treatment access is equal (Fillmore, Blood 2019; Dong, Blood Cancer J 2022). DETERMINATION included one of the largest cohorts of AA pts in prospective NDMM trials (n=132/722, 18.3%). The overall progression-free survival (PFS) difference (RVd-alone vs RVd+ASCT; median 46.2 vs 67.5 months [mos]; hazard ratio [HR] 1.53) was not seen in AA pts (HR 1.07; Richardson, N Engl J Med 2022). Multivariable PFS analyses, overall and by arm, showed that prognostic factors may vary according to treatment received, potentially indicating differences in MM pathobiology; PFS in AA vs White pts was longer with RVd-alone (HR 0.58) but similar with RVd+ASCT (HR 0.95) (Hassoun, EBMT 2023). We build upon this prior work with new analyses to explore outcomes with RVd-alone vs RVd+ASCT in AA and White pts. Methods Pts aged 18-65 y received RVd (3 cycles), stem cell mobilization, then 5 more RVd cycles (RVd-alone: n=357; 66 AA, 268 White) or ASCT and 2 more RVd cycles (RVd+ASCT: n=365; 66 AA, 272 White), and then R maintenance. We analyzed PFS (primary endpoint) by race, with exploration of potentially confounding effects of body mass index (BMI) and sex. Treatment exposure, response, event-free survival (EFS; events: progressive disease [PD], death, non-protocol therapy [NPT]), OS, and safety by race were evaluated. Exploratory genomic analyses in a subset of pts assessed frequency of Duffy-null genotype, a common variant in AA pts associated with lower circulating neutrophil count without increased infection risk that may have a key role in cytokine homeostasis (Jinna, Cells 2022). Results AA pts were younger and more commonly female than White pts, as seen in the GRIFFIN study (Nooka, Blood Cancer J 2022), with higher rates of ECOG PS &amp;gt;0, BMI ≥30, LDH &amp;gt;ULN, and low hemoglobin (panel A). Of 153 samples tested to date, 13 (8.5%) were Duffy-null: 11/17 (64.7%) AA and 2/136 (1.5%) non-AA pts. Median treatment duration from randomization (cycle 2) in AA and White pts, respectively, was 27.5 and 28.7 mos (RVd-alone) vs 36.1 and 36.2 mos (RVd+ASCT); 16% of AA and 13% of White pts discontinued within the first 3 RVd cycles due to adverse events (AEs; 5%/3% of AA/White pts), pt/investigator decision (5%/6%), PD (3%/3%), death (2%/&amp;lt;1%), or other reasons (2%/1%). In the 79%/86% of AA/White pts (RVd+ASCT) who underwent ASCT on study, transplant parameters were similar. 77%/83% of AA/White pts on the RVd-alone arm and 74%/80% on RVd+ASCT started R maintenance; median duration was 43.3/35.8 mos and 45.2/40.4 mos, respectively. In AA/White pts, median % of cycles with mean R dose &amp;gt;10 mg was 78%/88% (RVd-alone) and 83%/58% (RVd+ASCT). At data cut-off, of pts who started maintenance, 35%/25% of AA/White pts on the RVd-alone arm and 35%/29% on the RVd+ASCT arm were ongoing, and 65%/75% and 65%/71% had discontinued (including 37%/57% and 33%/37% due to PD), respectively. AE data are shown in panel B. Odds of achieving ≥CR were greater with RVd-alone vs RVd+ASCT in AA pts and were lower for AA vs White pts on the RVd+ASCT arm (panel B). Median PFS (RVd-alone vs RVd+ASCT) was not reached (NR) vs 61.4 mos (HR 1.07) in AA pts and 44.3 vs 67.2 mos (HR 1.67) in White pts. PFS with RVd-alone vs RVd+ASCT was longer in AA pts with BMI ≥30 (median NR vs 58.6 mos, HR 0.74), but shorter in AA pts with BMI &amp;lt;30 (66.4 mos vs NR, HR 1.86) and White pts with BMI &amp;lt;30 (45.3 vs 82.3 mos, HR 1.78) or ≥30 (41.1 vs 64.4 mos, HR 1.58). The PFS with RVd-alone vs RVd+ASCT was similar in male (HR 1.28) and female (HR 0.90) AA pts but shorter in male (HR 1.47) and female (HR 1.85) White pts. With RVd-alone vs RVd+ASCT, median EFS was 47.7 vs 48.2 mos (HR 0.99) in AA pts and 31.7 vs 46.7 mos (HR 1.30) in White pts; 5-y OS was 83.2% vs 78.7% (HR 0.99) in AA pts and 77.1% vs 80.3% (HR 1.08) in White pts. Among AA/White pts off study treatment, 64%/77% had received NPT; 27%/28% (RVd-alone arm) had received ASCT as NPT. Conclusions Our analyses suggest that PFS, EFS, and OS were similar with RVd-alone and RVd+ASCT in AA pts on this study. Importantly, while outcomes with RVd+ASCT were similar in AA and White pts, exploratory analyses suggest AA pts with high BMI and female AA pts may derive more PFS benefit from RVd-alone. Rates of starting maintenance/NPT use were lower in AA vs White pts, but maintenance duration proved longer in AA pts, with similar rates of grade ≥3 hematologic AEs, including neutropenia; analyses of outcomes by Duffy status are ongoing and will be presented.

Buprenorphine-naloxone, Buprenorphine, and Methadone Throughout Pregnancy in Maternal Opioid Use Disorder

(Acta Obstet Gynecol Scand. 2023;102:313–322) Maternal opioid use disorder (MOUD) is a global concern. It poses many complications and risk factors for mothers, fetuses, and infants. Mothers are at risk of experiencing negative effects on the nervous system, increased infection risk, and poor nutrition. Children are at risk for neonatal opioid withdrawal syndrome (NOWS) and other long-term health conditions. It is recommended that mothers obtain opioid maintenance treatment (OMT) to reduce these risks. This study aimed to compare the effects of buprenorphine-naloxone, buprenorphine, and methadone treatment plans on outcomes for pregnant women.

Effects of Everolimus in Modulating the Host Immune Responses against Mycobacterium tuberculosis Infection.

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (P13K/AKT/mTOR) pathway plays a key role in tuberculosis (TB) pathogenesis and infection. While the activity levels of this pathway during active infection are still debated, manipulating this pathway shows potential benefit for host-directed therapies. Some studies indicate that pathway inhibitors may have potential for TB treatment through upregulation of autophagy, while other studies do not encourage the use of these inhibitors due to possible host tissue destruction by Mycobacterium tuberculosis (M. tb) and increased infection risk. Investigating further clinical trials and their use of pathway inhibitors is necessary in order to ascertain their potential for TB treatment. This paper is particularly focused on the drug everolimus, an mTOR inhibitor. One of the first clinical trials sponsored by the Aurum Institute showed potential benefit in using everolimus as an adjunctive therapy for tuberculosis. Infection with tuberculosis is associated with a metabolic shift from oxidative phosphorylation towards glycolysis. The everolimus arm in the clinical trial showed further reduction than the control for both maximal and peak glycolytic activity. Compared with control, those receiving everolimus demonstrated increased lung function through forced expiratory volume in 1 s (FEV1) measurements, suggesting that everolimus may mitigate inflammation contributing to lung damage.

Combination Foley Catheter-Oxytocin versus Oxytocin Alone following Preterm Premature Rupture of Membranes.

The benefit of mechanical ripening agents following preterm premature rupture of membranes (PPROM) has not been established. We sought to compare the time to delivery in women who received transcervical Foley catheter plus oxytocin infusion versus oxytocin infusion alone in patients with unfavorable cervices and PPROM. This is a retrospective cohort study of patients presenting with PPROM of a live, singleton gestation between 240/7 and 366/7 weeks' gestation from January 2005 to October 2018 at a single, tertiary care institution. Patients with an unfavorable cervical examination (≤2-cm dilation), no contraindication to labor and undergoing labor induction were analyzed. Time to delivery was analyzed using multivariable linear regression adjusting for cervical dilation at induction and nulliparity. Bivariate and multivariate analyses were used where appropriate. A total of 260 participants were included: 109 who received a Foley catheter and oxytocin (Foley/oxytocin) and 151 who had oxytocin alone. Demographic characteristics were similar between the two groups. Unadjusted time to delivery was significantly shorter in the oxytocin only group (Foley/oxytocin: 20.35 hours vs. oxytocin alone: 14.7 hours, p < 0.001). No differences in length of labor were detected after adjusting for cervical dilation at induction and nulliparity (p = 0.5). The unadjusted rate of cesarean delivery was higher in the combination Foley/oxytocin group (Foley/oxytocin: 16.5% vs. oxytocin alone: 7.3%, p = 0.03), but no differences were found in the adjusted analysis (p = 0.06). There were no differences in clinical chorioamnionitis rates between the two groups (Foley/oxytocin: 8.3% vs. oxytocin alone: 9.3%, p = 0.83). Furthermore, no significant differences were found in maternal and neonatal outcomes between the two groups. In patients with PROM, the use of a transcervical Foley catheter in addition to oxytocin is not associated with a shorter time to delivery compared with oxytocin alone. · Transcervical Foley catheter did not shorten length of labor in PPROM.. · Transcervical Foley catheter did not increase infection risk.. · Pitocin alone can be used in PPROM population..

Abstract 14884: Variation of Immune Function Assay Within the First Year After Heart Transplantation

Introduction: The ImmuKnow® immune function assay (IFA) is used in heart transplant recipients to measure lymphocyte-mediated cell immunity via CD4 cell ATP production. Values &lt;225 ng/mL are associated with increased infection risk; however, serial changes in the first year after heart transplant are not well reported. We evaluated IFA trends for heart transplant recipients over the first year after transplantation. Methods: This is a single-center cohort study of consecutive heart transplant recipients from 1/1/2014-8/31/2022 that had an IFA obtained within 30-days of transplant and &gt;1 subsequent IFA within the first year after transplant. We described the relative and absolute change of mean IFA in 90-day increments through the first year after transplant, including sex specific differences. Multivariable logistic regression models tested the independent association of patient-level clinical characteristics factors with IFA values &lt;225 ng/mL. Results: In the study cohort, (121/315) (38%) had an IFA within 30-days prior to transplant. Most patients were white non-Hispanic (46%) and male (74%). IFA values decreased from the pre-transplant baseline with mean absolute changes of 92 ng/mL (-24%), 120 ng/mL (-31%), 121 ng/mL (-32%), and 114 ng/mL (-28%) every 90 days after transplant, respectively (panel B). The highest prevalence of an IFA value &lt;225 ng/mL occurred 90-180 days post-transplant in 55/103 (53%) patients. Female patients had a greater absolute and relative decrease in IFA values from baseline and each 90-day period (panel C). In exploratory analysis, at the time of transplant age &gt;60 was associated with a lower risk of IFA values &lt;225 during days 90-180 post-transplant (OR 0.24, p=0.02). A creatinine &gt;1.4 mg/dL was associated with IFA values &lt;225 during 90-180 (OR 3.15, p=0.02) and 180-270 (OR 3.44, p=0.03) days. Conclusion: Heart transplant recipients experienced ~25% reduction in IFA value from baseline in the first-year post-heart transplant.