Risk Of Infection Research Articles

Imaging of Central Nervous System Infections in the Immunocompromised Patient

Immunocompromised patients are susceptible to the same infections as immunocompetent individuals and have an additional unique risk for atypical infections in the central nervous system (CNS). Many CNS infections carry a poor prognosis if not treated promptly, so it is prudent for radiologists to recognize key findings and have a high level of suspicion in immunocompromised patients. Moreover, a patient may have no known deficiency but can present with an atypical CNS infection as their first sign of an immunocompromised state, thus allowing the radiologist to be the first to suggest specific workup such as HIV testing. Because different infection sources (bacterial, fungal, and parasitic) have separate treatments, it is highly valuable to guide management in the right direction early in the diagnostic workup. This article discusses common opportunistic infections observed in the immunocompromised patient, primarily focusing on neuroimaging findings and pertinent clinical background and treatment for each disease entity. This article also emphasizes the importance of familiarity with the differential diagnosis for ring-enhancing lesions within the CNS.

Alemtuzumab induction is associated with decreased hospitalization rates in pediatric kidney transplant: A UNOS data review for safety and outcomes with common induction regimens.

We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents. Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001). Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.

Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases

The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID‐19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.

Urinary catheterization during laparoscopic inguinal hernia repair: Really necessary or a habit?

BackgroundDuring laparoscopic inguinal hernia repair (LIH) repair, it is common practice to insert a urinary catheter (UC) to mitigate the risk of bladder injury or acute postoperative urinary retention. However, this procedure often leads to potential complications or infections. This study aims to evaluate the implications of the UC placement during LIH repair. MethodsThis retrospective, monocentric study included patients who underwent LIH repair between 01/01/2018 to 31/12/2022. Patients were divided into two groups: UC and no-UC. Results212 patients were included: 119 (56 %) in the no-UC group and 93 (44 %) in the UC group. The UC group presented a higher prevalence of bilateral hernias (38.7 % vs. 52.7 %), (p=0.01) and a greater frequency of intraperitoneal approach (TAPP) (83.9 % vs. 100 %), (p=0.01). No intraoperative complications were attributable to the absence of the UC. Four patients in the UC group had postoperative acute urinary retention necessitating intermittent catheterization, allowing discharge (p = 0.13). Rates of readmission and reoperation rates were comparable between groups. One month post-surgery, 7.5 % of UC group patients (vs. 0.8 %) developed urinary tract infection (p=0.01). Subgroup analysis confirmed a higher incidence of urinary tract infections in unilateral hernia and in TAPP procedure. ConclusionRoutine UC insertion during LIH repair seems unnecessary; rather, it increases the risk of postoperative urinary tract infections and should thus be avoided.

Cost-effectiveness of One Health intervention to reduce risk of human exposure and infection with non-typhoidal salmonellosis (NTS) in Nigeria.

Non-typhoidal Salmonella infection (NTS) is an important foodborne zoonosis with underappreciated health and economic burdens, and low case fatality. It has global prevalence, with more burdens in under-resourced countries with poor health infrastructures. Using a cohort study, we determined the cost-effectiveness of NTS in humans in Nigeria for the year 2020. Using a customized Excel-based cost-effectiveness analysis tool, structured (One Health) and unstructured (episodic intervention against NTS) in Nigeria were evaluated. Input data on the disease burdens, costs surveillance, response and control of NTS were obtained from validated sources and the public health system. The non-complicated and complicated cases were 309,444 (95%) and 16,287 (5%) respectively, and the overall programme cost was US$ 31,375,434.38. The current non-systematic episodic intervention costed US$ 14,913,480.36, indicating an additional US$ 16,461,954 to introduce the proposed intervention. The intervention will avert 4036.98 NTS DALYs in a single year. The non-complicated NTS case was US$ 60/person with significant rise in complicated cases. The cumulative costs of NTS with and without complications far outweighed the program cost for One Health intervention with an incremental cost-effectiveness ratio (ICER) of -US$ 221.30). Utilising structured One Health intervention is cost-effective against NTS in Nigeria, it carries additional mitigative benefits for other diseases and is less costly and more effective, indicative of a superior health system approach. Identified limitations must be improved to optimize benefits associated and facilitate policy discussions and resource allocation.

Assessment of COVID-19 Infection Risks in an Office Building: Field Study Investigation in Shenzhen, China

Assessment of COVID-19 Infection Risks in an Office Building: Field Study Investigation in Shenzhen, China

First Detection of the Jingmen Tick Virus in Amblyomma testudinarium Ticks from the Kanto Region, Japan.

In 2010, Jingmen tick virus (JMTV) was discovered in ticks in China and has been shown to be distributed in several regions worldwide. Recently, cases of JMTV infection in humans have been reported in China and Kosovo, and have attracted much attention as an emerging tick-borne disease. In this study, we detected the JMTV genome in Amblyomma testudinarium ticks collected in Kanagawa Prefecture, Japan, during tick-borne virus surveillance conducted in the Kanto Region. Phylogenetic analysis revealed that the new JMTV strain was closely related to previous strains detected in Japan. This suggests that JMTV may have been maintained during an independent natural transmission cycle in Japan. In addition, unlike other countries and regions, all JMTV strains in Japan were detected only in A. testudinarium ticks, suggesting that this tick species is the primary JMTV vector in Japan. This is the first report of JMTV in the Kanto Region. Further studies are required to elucidate the potential risk of infection with this tick-borne virus in Japan. In particular, the prevalence of JMTV in wild animals should be examined to clarify its geographical distribution, host range, and transmission cycle.

Naive Bayes - Random Forest Ensemble Model Analysis and Heart Disease Prediction

Abstract: The critical task of accurately diagnosing heart disease can potentially save lives. Leveraging the UCI machine learning heart disease dataset and employing ensemble machine learning techniques, including Gausian Naive Bayes and Random Forest algorithms, the research investigates 13 primary characteristics to predict heart disease risks. The conventional machine learning approaches are utilized to analyze the dataset, unveiling correlations between features and heart infection risks. The aim is to develop a user-friendly interface, the Heart Disease Clinical Decision Support System (HDCDSS), where patients input their clinical details to receive a predictive analysis of their coronary disease. The system, built in Python with Flask and Bootstrap, provides clients with personalized reports on their heart health, enhancing diagnostic accuracy and potentiallystreamlining healthcare processes.

Antibiotic-Impregnated Ventriculoperitoneal Shunts Decrease Bacterial Shunt Infection: A Systematic Review and Meta-Analysis.

Antibiotic-impregnated shunts seem to be beneficial in preventing bacterial infections and decreasing mortality by effectively inhibiting microbial growth in the shunt system and reducing the risk of shunt-associated infections. This study aimed to evaluate the efficacy of antibiotic-impregnated shunt catheters (AISC) in reducing the incidence of bacterial shunt infection in patients with hydrocephalus. The protocol was registered on PROSPERO. A meta-analysis was conducted by searching 3 databases (PubMed, Scopus, CENTRAL) for relevant randomized controlled trials and observational studies. We included all studies published until November 2022 in any language. The primary outcome was the rate of bacterial infections, whereas the rate of shunt failure was our secondary endpoint. Odds ratios (OR) with 95% CI were calculated using a random-effects model. A total of 27 articles with 27 266 shunt operations were included in this study. The results indicated that using AISC is significantly associated with reduction in infections (OR = 0.42; 95% CI: 0.33-0.54). Regarding shunt failure, there was a tendency in favor of AISC use (OR = 0.73; 95% CI: 0.51-1.06). Our study provided evidence that AISC is significantly associated with the reduction in the rate of bacterial ventriculoperitoneal-shunt infection. In addition, there was a tendency toward AISC to decrease shunt failure compared with the standard shunt.

Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Risk of surgical site infection after hip hemiarthroplasty of femoral neck fractures: a systematic review and meta-analysis.

Surgical site infection (SSI) is a major complication following hemiarthroplasty surgery for displaced neck of femur fractures. Our aim is to systematically analyse relevant peer-reviewed studies for recent clinical information on the quantitative risk of surgical site infection (SSI) after hemiarthroplasty (HA) of hip fracture patients and on the factors which influence the SSI rates. A comprehensive search of electronic databases (PubMed, Cochrane) was performed for clinical articles published between 2005 and 2023 and systematically reviewed with a defined list of inclusion and exclusion criteria. The methodology was undertaken and reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement checklist, while the detailed search strings and study protocol were published in PROSPERO (CRD42023458150). The pooled risks of SSIs were calculated in both primary and subgroup analyses. The primary analysis showed a pooled superficial SSI rate after hemiarthroplasty of 1.3% (95% confidence interval (CI) 0.71; 2.04) from 17 studies with 29,288 patients and a deep SSI rate of 2.14% (1.87; 2.42) from 29 studies with 192,392 patients. Higher infection rates were observed with longer follow-up periods for deep SSI: pooled rates increased from 1.24% (0.73; 1.87) at 1 month to 2.64% (2.03; 3.31) at 12 months. Additionally, studies using defined criteria for infection diagnosis reported higher rates compared to undefined criteria: pooled deep SSI rates were 2.91% (1.40; 4.92) vs. 0.62% (0.34; 0.96) for defined vs. undefined criteria respectively, and 3.18% (2.23; 4.29) vs. 1.7% (1.44; 1.99) for superficial SSI. The results of this study demonstrate a substantial SSI risk and a high variability of the infection rates following hemiarthroplasty for hip fracture patients. A standardization of infection criteria and an extended follow-up period are advisable and should be considered in guidelines aimed at improving the standard of care for these patients.

Dengue virus exploits autophagy vesicles and secretory pathways to promote transmission by human dendritic cells

Dengue virus (DENV), transmitted by infected mosquitoes, is a major public health concern, with approximately half the world’s population at risk for infection. Recent decades have increasing incidence of dengue-associated disease alongside growing frequency of outbreaks. Although promising progress has been made in anti-DENV immunizations, post-infection treatment remains limited to non-specific supportive treatments. Development of antiviral therapeutics is thus required to limit DENV dissemination in humans and to help control the severity of outbreaks. Dendritic cells (DCs) are amongst the first cells to encounter DENV upon injection into the human skin mucosa, and thereafter promote systemic viral dissemination to additional human target cells. Autophagy is a vesicle trafficking pathway involving the formation of cytosolic autophagosomes, and recent reports have highlighted the extensive manipulation of autophagy by flaviviruses, including DENV, for viral replication. However, the temporal profiling and function of autophagy activity in DENV infection and transmission by human primary DCs remains poorly understood. Herein, we demonstrate that mechanisms of autophagosome formation and extracellular vesicle (EV) release have a pro-viral role in DC-mediated DENV transmission. We show that DENV exploits early-stage canonical autophagy to establish infection in primary human DCs. DENV replication enhanced autophagosome formation in primary human DCs, and intrinsically-heightened autophagosome biogenesis correlated with relatively higher rates of DC susceptibility to DENV. Furthermore, our data suggest that viral replication intermediates co-localize with autophagosomes, while productive DENV infection introduces a block at the late degradative stages of autophagy in infected DCs but not in uninfected bystander cells. Notably, we identify for the first time that approximately one-fourth of DC-derived CD9/CD81/CD63+ EVs co-express canonical autophagy marker LC3, and demonstrate that DC-derived EV populations are an alternative, cell-free mechanism by which DCs promote DENV transmission to additional target sites. Taken together, our study highlights intersections between autophagy and secretory pathways during viral infection, and puts forward autophagosome accumulation and viral RNA-laden EVs as host determinants of DC-mediated DENV infection in humans. Host-directed therapeutics targeting autophagy and exocytosis pathways thus have potential to enhance DC-driven resistance to DENV acquisition and thereby limit viral dissemination by initial human target cells following mosquito-to-human transmission of DENV.

Clinical Characteristics and Outcomes of Disseminated Strongyloidiasis in the United States-A Multicenter Network Analysis.

Human strongyloidiasis is a potentially life-threatening parasitic disease among immunocompromised hosts. We aim to determine the factors and mortality associated with disseminated strongyloidiasis. We conducted a U.S.-based multicenter retrospective cohort study to determine 90-day clinical outcomes for people diagnosed with Strongyloides infection in the TriNetX patient database. We identified adult patients with the International Classification of Diseases (10th revision, clinical modification) code for Strongyloides infection (B78) or a positive Strongyloides IgG antibody test and captured outcomes at 90 days. We identified 5,434 patients with strongyloidiasis, of whom 48 had disseminated strongyloidiasis for 0.9% prevalence of disseminated disease. Systemic connective tissue disorders, pulmonary eosinophilia, liver cirrhosis, blood disorders (monoclonal gammopathy, aplastic anemia, and lymphoid malignancy), malnutrition, alcohol use disorder, and transplantation status were frequent in patients with disseminated disease. Mortality was significantly higher in people with disseminated disease at 30 days (21%). The 90-day risk of hospitalization, bacteremia, and acute respiratory distress syndrome (ARDS) was higher in those with disseminated infection. People with disseminated strongyloidiasis had a heightened risk of hospitalization, bacteremia, acute respiratory distress syndrome, and mortality. The population at risk for severe strongyloidiasis infection is evolving, reflecting conditions in which glucocorticoids or additional immunosuppressive medications are commonly used for treatment.

COVID-19 infection in children, adolescents, and young adults with Down syndrome and hematologic malignancies.

Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population. This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy. Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p<.001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR]=2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR=4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR=4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p=.001), but not when unrelated to neutropenia (p=.88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR=1.20, 95% CI: 0.7-2.1). We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19.

Pre- and Post-Exposure Prophylaxis for HIV in Patients Taking Anti-Seizure Medications

The prevention of human immunodeficiency virus (HIV) infection has recently emphasized the use of pre- and post-exposure prophylaxis (PrEP and PEP), both of which were highly effective in prevention of HIV infection. Since the last published guidance regarding the cotreatment of people with anti-seizure medications (ASM) and antiretroviral treatments (ARTs) in 2012, both fields have numerous new medication options. Historically, cotreatment of HIV and seizures could be challenging with increased risk of virologic failure and barriers in access to health care due to global availability, social determinants of health, and stigma of both HIV and seizures. In this narrative review, we describe the data-driven and expected bidirectional pharmacokinetic (PK) interactions between guideline-based PrEP and PEP treatment and ASM, as well as overlapping side effects. There are many ASMs with no known interaction with PrEP or PEP regimens. The interactions focus on enzyme inducing ASMs, valproate, and lamotrigine. Most prominently, enzyme inducing ASMs lower serum levels of tenofovir-containing PrEP regimens and elements of PEP (dolutegravir, raltegravir, and ritonavir), which increased risk of virologic treatment failure in people with HIV but have unclear clinical significance on the effectiveness of PrEP and PEP. In addition, ritonavir treatment in PEP may significantly lower lamotrigine serum levels even during the 4 weeks of treatment, which may increase risk for breakthrough seizures during PEP and skin reactions after discontinuation of ritonavir. In addition to PK interactions, overlapping side effects are common including osteopenia, hepatic toxicity, and other gastrointestinal effects. This narrative review aims to be a resource for all clinicians prescribing ASMs so that they can create a welcoming environment to enable successful treatment of seizures and reduce the risk of HIV infection in people at risk. In addition, we highlight knowledge gaps and areas of unmet need that can be addressed with future studies.

Homophily and social mixing in a small community: Implications for infectious disease transmission.

Community mixing patterns by sociodemographic traits can inform the risk of epidemic spread among groups, and the balance of in- and out-group mixing affects epidemic potential. Understanding mixing patterns can provide insight about potential transmission pathways throughout a community. We used a snowball sampling design to enroll people recently diagnosed with SARS-CoV-2 in an ethnically and racially diverse county and asked them to describe their close contacts and recruit some contacts to enroll in the study. We constructed egocentric networks of the participants and their contacts and assessed age-mixing, ethnic/racial homophily, and gender homophily. The total size of the egocentric networks was 2,544 people (n = 384 index cases + n = 2,160 recruited peers or other contacts). We observed high rates of in-group mixing among ethnic/racial groups compared to the ethnic/racial proportions of the background population. Black or African-American respondents interacted with a wider range of ages than other ethnic/racial groups, largely due to familial relationships. The egocentric networks of non-binary contacts had little age diversity. Black or African-American respondents in particular reported mixing with older or younger family members, which could increase the risk of transmission to vulnerable age groups. Understanding community mixing patterns can inform infectious disease risk, support analyses to predict epidemic size, or be used to design campaigns such as vaccination strategies so that community members who have vulnerable contacts are prioritized.

Examining pancreatic stone protein response in ICU-acquired bloodstream infections: a matched event analysis.

Pancreatic stone protein (PSP) exhibits potential as a plasma biomarker for infection diagnosis and risk stratification in critically ill patients, but its significance in nosocomial infection and intensive care unit (ICU)-acquired bloodstream infection (BSI) remains unclear. This study explores the temporal responses of PSP in ICU-acquired BSI caused by different pathogens. From a large cohort of ICU patients, we selected episodes of ICU-acquired BSI caused by Gram-negative rods (GNRs), enterococci, or Candida species. Events were matched on length of ICU stay at infection onset, Severe Organ Failure Assessment (SOFA) score, presence of immune deficiency, and use of renal replacement therapy. PSP concentrations were measured at infection onset (T0) and at 24, 48 and 72h prior to infection onset as defined by the first occurrence of a positive blood culture. Absolute and trend differences in PSP levels between pathogen groups were analysed using one-way analysis of variance. Sensitivity analyses were performed in events with a new or worsening systematic inflammatory response based on C-reactive protein, white cell count and fever. We analysed 30 BSI cases per pathogen group. Median (IQR) BSI onset was on day 9 (6-12). Overall, PSP levels were high (381 (237-539) ng/ml), with 18% of values exceeding the assay's measurement range. Across all 90 BSI cases, there was no clear trend over time (median change 34 (- 75-189) ng/ml from T-72 to T0). PSP concentrations at infection onset were 406 (229-497), 350 (223-608), and 480 (327-965) ng/ml, for GNR, enterococci, and Candida species, respectively (p = 0.32). At every time point, absolute PSP levels and trends did not differ significantly between pathogens. PSP values at T0 correlated with SOFA scores. Eighteen (20%) of 90 BSI events did not exhibit a systemic inflammatory response, primarily in Candida species. No clear change in PSP concentration before BSI onset or between-group differences were found in sensitivity analyses of 72 cases. Against a background of overall (very) high plasma PSP levels in critically ill patients, we did not find clear temporal patterns or any pathogen-specific differences in PSP response in the days preceding onset of ICU-acquired BSI.

Robot-Assisted Radical Prostatectomy in PIRADS 5 Lesions Without Prior Biopsy: Is Biopsy Really Necessary in This Cohort?

Introduction: Conventionally, confirmation of clinically significant prostate cancer (csPCa) (Gleason grade group ≥ 2) involves an initial multiparametric magnetic resonance imaging (mpMRI) followed by biopsy. Prostate biopsy incurs inherent risks of infection, bleeding, patient discomfort, and a 6-week delay before robot-assisted laparoscopic radical prostatectomy (RALP). We explored the feasibility of immediate RALP in men with PIRADS 5 lesions without preceding biopsy. Methodology: After obtaining institutional review board approval, a prospective analysis was conducted on 235 patients with PIRADS 5 lesions on mpMRI from December 2018 to February 2023. Patients were divided into 2 groups as follows: Group NoBiopsy (biopsy not done before RALP, cases, n = 118) and Group YesBiopsy (biopsy done before RALP, controls, n = 117). Baseline preoperative, intraoperative, and postoperative parameters were analyzed. Functional outcomes were monitored at 1, 3-, 6-, 9-, and 12-months follow-up post-RALP. Statistical analysis was performed using SPSS and STATA. Results: Ninety-five percent of cases and 87.17% controls had csPCa on final pathology post-RALP. Multivariable analysis did not find significant association between biopsy status and csPCa. Abnormal digital rectal examination (DRE), family history, preoperative PSA, and MRI lesion volume predicted csPCa. Significant differences were observed in console time (NoBiopsy vs. YesBiopsy, 60 ± 10 vs. 70 ± 9 minutes, p < 0.001) and estimated blood loss (80 ± 20 vs. 100 ± 30 mL, p < 0.01) between groups. At 6 months post-RALP, 96% of men in Group NoBiopsy were continent, compared with 88% of men in Group YesBiopsy (p < 0.04). All men in the study cohort were continent (0 pads) at 12 months post-RALP. Ninety-eight percent of cases and 92% of controls at 9 months and 12 months, respectively, were able to have penetrative sex with or without PDE-5 inhibitors post-RALP. Conclusion: RALP without antecedent prostate biopsy in men with PIRADS 5 lesions demonstrated substantial csPCa detection rates and superior functional outcomes, warranting further validation.

Optimizing Healthcare Expenditure for Spinal Cord Stimulation in Italy: The Value of Battery Longevity Improvement and a Direct-to-Implant Approach

Background: Spinal cord stimulation (SCS) is a treatment for chronic intractable pain powered by an implantable pulse generator that may be rechargeable or not rechargeable (NR). It is performed in 2 stages (a trialing phase followed by permanent device implantation) and necessitates 2 hospitalizations, which may increase infection risk. Objective: This analysis explores the cost impact of improvements in battery longevity and the adoption of 1-step (direct-to-implant [DTI]) SCS implantation. Methods: Since 2019, 3 leading NR-SCS devices have been launched: Device A (2019), Device B (2020), and Device C (2021). The battery longevity of the newest Device C was estimated at comparable stimulation settings for Devices A and B. A Markov model simulated individual patient pathways across 2 scenarios: Device A vs Device C and Device B vs Device C (both with the DTI approach and 2-step approach). Costs considered were the initial device implantation procedure, device replacements, and serious adverse event (SAE) management. Italian diagnosis-related group (DRG) tariffs were applied for costs, and a 15-year time horizon was used. Results: Over 15 years, using a DTI approach, the undiscounted total costs for Device A vs Device C were €26 860 and €22 633, respectively, and €25 111 and €22 399 for Device B vs Device C, respectively. Compared with Devices A and B, Device C offered savings of €4227 and €2712, respectively; similar savings were predicted with a 2-step implant approach. Discussion: The battery longevity of NR-SCS devices directly impacts long-term costs to a payer. The longer the device lasts, the lower mean total cumulative costs the patient will have, especially with regard to device replacement costs. With novel devices and specific programming settings, the lifetime cost per patient to a payer can be decreased without compromising the patient’s safety and positive clinical outcome. Conclusions: Extended SCS battery longevity can translate into tangible cost savings for payers. The DTI approach for SCS supports National Healthcare System cost efficiencies and offers the additional benefits of optimizing operating room time while having only one recovery period for the patient.

Comparing the risk of death, major adverse cardiac events, and relapse in bullous pemphigoid patients treated with systemic or topical corticosteroids.

According to current guidelines, systemic or topical corticosteroids are recommended as first-line treatments for bullous pemphigoid (BP). There is evidence suggesting that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections, and relapse, between systemic and topical corticosteroid treatments. To evaluate the risk of death, MACE, infections, and relapse in BP patients treated with systemic or topical corticosteroids. A population-based retrospective cohort study was performed in the TriNetX US Collaborative Network. As a measure against bias, propensity-score matching for age, sex, ten diseases and six medications, and three sensitivity analyses were conducted. All-time risk of death was increased in US BP patients exposed to any dose of systemic corticosteroids (n=2,917) compared to topical clobetasol propionate treated patients (n=2,932, hazard ratio [HR], 1.43, 95% confidence interval [CI] 1.28-1.58, p<0.0001). This was consistent in time-stratified analysis (1- and 3-year mortality rates), and in analysis contrasting prednisone (equivalent) does of 1-10 mg (low) or 30-100 mg (medium-high) systemic corticosteroid to topical treatment. The increased risk of death in US BP patients exposed to any dose of systemic corticosteroids compared to topical treatment was accompanied by increased risks for MACE (HR 1.33, CI 1.08-1.64, p=0.0075) and infections (HR 1.33, CI 1.15-1.54, p=0.0001). The risk of continued disease or relapse was decreased in patients treated with systemic as opposed to topical corticosteroid (HR 0.85, CI 0.77-0.94, p=0.0016). Results regarding mortality and continued disease or relapse persisted in three of three sensitivity analyses. Potential limitations are the retrospective data collection, bias for treatment selection and miscoding. Pending validation in prospective studies, where feasible, and despite the heightened risk of relapse, topical corticosteroid treatment may be advantageous compared to systemic corticosteroid treatment due to its significantly lower risk of death.