Comparison of infection risk between enzalutamide and abiraterone in patients with prostate cancer

Background Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. Methods Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). Results Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow-up of 10.6 months (interquartile range: 5.3–19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53–0.93], p = .014), pneumonia (adjusted SHR 0.76 [0.59–0.99], p = .040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39–0.79], p = .001), but not urinary tract infection (adjusted SHR 0.91 [0.62–1.35], p = .643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. Conclusions Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess

A 2-year prospective evaluation of the Prostate Health Index in guiding biopsy decisions in a large cohort

Objectives: To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real-life setting for men with a prostate-specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. Patients and Methods: Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow-up plan was then decided via shared decision-making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. Results: A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score &lt;35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score &lt;35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score &lt;35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score &lt;35 group (13%) with a median follow-up of 2.4 years. Conclusion: In a real-life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high-grade prostate cancer detection rate when compared to PSA-driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow-up visits.</p

Development of a human-size magnetic particle imaging device for sentinel lymph node biopsy of breast cancer

In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8 [email protected] mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100 dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30 mm in the Z direction, and the sensitivity was about 10 μg Fe SPIONs at 40 mm distance with a spatial resolution of about 5 mm. In the rat experiment, 54 μg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6 min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future

Comparison of infection risk between enzalutamide and abiraterone in patients with prostate cancer

Background: Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. Methods: Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time‐to‐event outcomes (multivariable Fine‐Gray regression, with mortality considered a competing event) and recurrent‐event outcomes (multivariable negative binomial regression). Results: Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow‐up of 10.6 months (interquartile range: 5.3–19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53–0.93], p = .014), pneumonia (adjusted SHR 0.76 [0.59–0.99], p = .040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39–0.79], p = .001), but not urinary tract infection (adjusted SHR 0.91 [0.62–1.35], p = .643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. Conclusions: Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Lack of Galanin 3 Receptor Aggravates Murine Autoimmune Arthritis

Neurogenic inflammation mediated by peptidergic sensory nerves has a crucial impact on the pathogenesis of various joint diseases. Galanin is a regulatory sensory neuropeptide, which has been shown to attenuate neurogenic inflammation, modulate neutrophil activation, and be involved in the development of adjuvant arthritis, but our current understanding about its targets and physiological importance is incomplete. Among the receptors of galanin (GAL1-3), GAL3 has been found to be the most abundantly expressed in the vasculature and on the surface of some immune cells. However, since there are minimal in vivo data on the role of GAL3 in joint diseases, we analyzed its involvement in different inflammatory mechanisms of the K/BxN serum transfer-model of autoimmune arthritis employing GAL 3 gene-deficient mice. After arthritis induction, GAL3 knockouts demonstrated increased clinical disease severity and earlier hindlimb edema than wild types. Vascular hyperpermeability determined by in vivo fluorescence imaging was also elevated compared to the wild-type controls. However, neutrophil accumulation detected by in vivo luminescence imaging or arthritic mechanical hyperalgesia was not altered by the lack of the GAL3 receptor. Our findings suggest that GAL3 has anti-inflammatory properties in joints by inhibiting vascular hyperpermeability and consequent edema formation

Research on Energy Management Strategy Based on Fuel Cell Health Status

Abstract Energy management control strategy is one of the key technologies in the development of extended-range fuel cell vehicles. During the use of vehicles, fuel cell performance will decline, which limits the power output of the stack and the life of the stack. In order to control the power output of the fuel cell more reasonably, in this paper, the lumped parameter model of fuel cell is built based on Matlab/Simulink, and the vehicle model is built by AVL/Cruise simulation software. Combined with the fuel cell health state (SOH: State of Health) estimation method, the vehicle demand power and the state of charge (SOC: State of Charge) value of the power battery are used as input, and an energy management control strategy architecture based on the performance degradation of the fuel cell is designed. The simulation results show that the designed energy management can improve dynamic performance, and avoid frequent start and stop of the fuel cell, prolong the service life of the fuel cell, and further improve the economy of the vehicle.</jats:p

Specificity Protein 1: A Protein With a Two-Sided Role in Ischemic Stroke

Stroke is one of the leading causes of death and disability worldwide. However, there is a lack of effective medications to speed up the recovery process. Ischemic stroke, as the result of cerebral infarction or cerebral artery narrowing, is accompanied by hemiplegia or impaired consciousness. There are many transcription factors involved in the development of this condition, whose alterations can influence or signal the prognostic outcomes of ischemic stroke. Among them, the augmented expression of specificity protein 1 (SP1) can participate in the progression of the disease by binding DNA to regulate the transcriptions of many genes. Different studies have provided different answers as to whether SP1 plays a positive or a negative role in ischemic stroke. On the one hand, SP1 can play a cytoprotective role as both an antioxidant and anti-apoptotic agent for neurons and glial cells. On the other hand, it can also damage neuronal cells by promoting inflammation and exacerbating brain edema. In this review, we highlight the roles of SP1 in ischemic stroke and shed light on the underlying mechanism.</jats:p