Risk Of Infection Research Articles

Infant Feeding for Persons Living With and at Risk for HIV in the United States: Clinical Report.

Pediatricians and pediatric health care professionals caring for infants born to people living with and at risk for HIV infection are likely to be involved in providing guidance on recommended infant feeding practices. Care team members need to be aware of the HIV transmission risk from breastfeeding and the recommendations for feeding infants with perinatal HIV exposure in the United States. The risk of HIV transmission via breastfeeding from a parent with HIV who is receiving antiretroviral treatment (ART) and is virally suppressed is estimated to be less than 1%. The American Academy of Pediatrics recommends that for people with HIV in the United States, avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission. However, people with HIV may express a desire to breastfeed, and pediatricians should be prepared to offer a family-centered, nonjudgmental, harm reduction approach to support people with HIV on ART with sustained viral suppression below 50 copies per mL who desire to breastfeed. Pediatric health care professionals who counsel people with HIV who are not on ART or who are on ART but without viral suppression should recommend against breastfeeding. Pediatric health care professionals should recommend HIV testing for all pregnant persons and HIV preexposure prophylaxis to pregnant or breastfeeding persons who test negative for HIV but are at high risk of HIV acquisition.

Two-year Monitoring of Microbiological Water Quality in Small Water Supply Systems: Implications for Microbial Risk Management.

Small water supply systems (SWSSs) are often more vulnerable to waterborne disease outbreaks. In Japan, many SWSSs operate without regulation under the Waterworks Law, yet there is limited investigation into microbial contamination and the associated health risks. In this study, the microbiological water quality of four SWSSs that utilize mountain streams as water sources and do not install water treatment facilities were monitored for over 2 years. In investigated SWSSs, the mean heterotrophic plate counts were below 350 CFU/mL, and the total bacterial loads (16S rDNA concentration) ranged from 4.71 to 5.35 log10 copies/mL. The results also showed the consistent presence of fecal indicator bacteria (FIB), i.e., Escherichia coli and Clostridium perfringens, suggesting the potential of fecal pollution. E. coli was then utilized as an indicator to assess the health risk posed by E. coli O157:H7 and Campylobacter jejuni. The results indicated that the estimated mean annual risk of infection and disability-adjusted life years (DALYs) exceeded acceptable levels in all SWSSs for the two reference pathogens. To ensure microbial water safety, implementing appropriate water treatment facilities with an estimated mean required reduction of 5-6 log10 was necessary. This study highlighted the potential microbial contamination and health risk level in SWSSs that utilize mountain streams as water sources, even though the water sources were almost not affected by human activities. Furthermore, this study would also be helpful in supporting risk-based water management to ensure a safe water supply in SWSSs.

Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review.

Biological drugs (BD) and Janus kinase inhibitors (JAKi) have revolutionized the treatment of diverse dermatoses. However, there are concerns regarding their safety, especially the risk of cancer and opportunistic infections. Here, we discuss the risk of cancer associated with the BD and JAKi used in dermatology. A narrative review was carried out. All relevant articles evaluating the risk of cancer associated with BD or JAKi and published between January 2010 and February 2024 were selected. Multiple large studies have evaluated the association between BD, JAKi and cancer risk. However, there is a lack of prospective, comparative studies. Overall, patients undergoing BD and JAKi present a cutaneous cancer incidence similar to that in the general population. The drugs more strongly associated with non-skin cancer risk were anti-tumor necrosis factor (anti-TNFs) agents and JAKi (especially tofacitinib and oral ruxolitinib). This risk appears to increase with age, the presence of other factors (such as chronic immunosuppression from previous drugs or other comorbidities), and specific diseases such as rheumatoid arthritis (RA) and myelodysplastic syndrome. Conversely, BD such as interleukin (IL)-17 and IL-23 inhibitors may even reduce the risk of some visceral and hematological malignancies. In patients with dermatological conditions such as psoriasis and atopic dermatitis, the risk of malignancies may be lower than in other subgroups, and probably comparable to the general population. The incidence of cancer in patients undergoing BD or JAKi is generally low. This incidence can be higher in elderly patients with RA or myelodysplastic syndrome, and in those undergoing prolonged therapy with tofacitinib or ruxolitinib (oral), or anti-TNF agents.

Justification for coercion in a public health crisis: not just a matter of individual harm.

The COVID pandemic was an exceptional public health situation - which brought with it unprecedented restrictions across the global populace. But what was it about this pandemic which caused us to implement such drastic restrictions on liberty? Much of the ethical debate on restrictive measures such as lockdowns and vaccine requirements focused on the potential harm that individuals cause to other individuals by the risk of infection. I will suggest that this may come from a reliance on J.S. Mill's harm principle as providing the ultimate justification for coercion - i.e., the well-accepted principle that state coercion is justified in order to prevent the imposition of unacceptable risk of harm to others. Though there have been attempts, in the wider public health ethics literature, to use the harm principle as a basis for restricting contribution to collective harms, I will suggest that these attempts cannot rely on the harm principle alone. I will then turn to the ways in which an individual-based line of reasoning does not capture a distinctive sort of harm posed by the COVID pandemic (and others like it): the potential failure of healthcare systems. I will draw out three ways in which a focus on the harm that an individual poses to another individual fails to capture the full scope of harm wrought by the collapse of healthcare systems. First, it can't adequately capture the cumulative and "looping effects" of the harm caused by strained healthcare systems. Second, it fails to capture the widespread ripple effects the failure of a central societal institution can have on other institutions. And third, the failure of a healthcare system can impose "psychic costs", affecting the moral character of all members of society, reducing trust in institutions, and potentially posing an existential threat to the fabric of society. Finally, I will sketch some implications of the recognition of this distinctive sort of harm for the justification of coercive public health measures.

Serum Albumin-to-Creatinine Ratio: A Novel Predictor of Pulmonary Infection in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

In patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), a low serum albumin-to-creatinine ratio (sACR) is associated with elevated risk of poor short- and long-term outcomes. However, the relationship between sACR and pulmonary infection during hospitalization in patients with STEMI undergoing PCI remains unclear. A total of 4,507 patients with STEMI undergoing PCI were enrolled and divided into three groups according to sACR tertile. The primary outcome was pulmonary infection during hospitalization, and the secondary outcome was in-hospital major adverse cardiovascular events (MACE) including stroke, in-hospital mortality, target vessel revascularization, recurrent myocardial infarction, and all-cause mortality during follow-up. Overall, 522 (11.6%) patients developed pulmonary infections, and 223 (4.9%) patients developed in-hospital MACE. Cubic spline models indicated a non-linear, L-shaped relationship between sACR and pulmonary infection (P=0.039). Receiver operating characteristic curve analysis indicated that sACR had good predictive value for both pulmonary infection (area under the ROC curve [AUC]=0.73, 95% CI=0.70-0.75, P＜0.001) and in-hospital MACE (AUC=0.72, 95% CI=0.69-0.76, P＜0.001). Kaplan-Meier survival analysis indicated that higher sACR tertiles were associated with a greater cumulative survival rate (P＜0.001). Cox regression analysis identified lower sACR as an independent predictor of long-term all-cause mortality (hazard ratio [HR]=0.96, 95% CI=0.95-0.98, P＜0.001). A low sACR was significantly associated with elevated risk of pulmonary infection and MACE during hospitalization, as well as all-cause mortality during follow-up among patients with STEMI undergoing PCI. These findings highlighted sACR as an important prognostic marker in this patient population.

Safety of early discharge after elective lumbar spine surgery with subfascial drains and association with significant reduction in length of stay.

After lumbar spine surgery, postoperative drain removal often delays discharge. Whether inpatient drain removal reduces the risk of surgical site infection (SSI) or hematoma remains controversial. Therefore, in patients undergoing elective lumbar spine surgery, the authors sought to determine the impact of inpatient versus outpatient drain removal on the following variables: 1) length of hospital stay (LOS), and 2) postoperative complications. A single-center retrospective cohort study in which the authors used prospectively collected data of patients undergoing primary, elective, 1- or 2-level lumbar spine decompression and/or fusion was undertaken between 2016 and 2022. Patients with intraoperative or postoperative CSF leaks were excluded. The primary exposure variable was inpatient versus outpatient drain removal. The primary outcome was LOS, and secondary outcomes were postoperative complications, including 90-day postoperative SSI or hematoma. Multivariable logistic and linear regression were performed, controlling for age, body mass index, instrumentation, number of levels, antibiotics at discharge, and surgeons involved. Of 483 patients included, 325 (67.3%) had inpatient drain removal and 158 (32.7%) had outpatient drain removal. Patients with outpatient drain removal were significantly younger (58.6 ± 12.4 vs 61.2 ± 13.2 years, p = 0.040); more likely to have 1-level surgery (75.9% vs 56.6%, p < 0.001); and less likely to receive instrumentation (50.6% vs 69.5%, p < 0.001). Postoperatively, patients with outpatient drain removal had a shorter LOS (0.7 ± 0.6 vs 2.3 ± 1.6 days, p < 0.001); were more likely to be discharged home (98.1% vs 92.3%, p = 0.015); were more likely to be discharged on antibiotics (76.6% vs 3.1%, p < 0.001); were less likely to be on opioids (32.3% vs 88.3%, p < 0.001); and were more likely to have Jackson-Pratt compared to Hemovac drains (96.2% vs 34.5%, p < 0.001). No difference was found in SSI (3.7% vs 3.8%, p > 0.999) or hematoma (0.9% vs 0.6%, p > 0.999), as well as reoperation or readmission due to SSI or hematoma. On multivariable regression, outpatient drain removal was significantly associated with shorter LOS (β = -1.15, 95% CI -1.56 to -0.73, p < 0.001). No association was found with SSI/hematoma (p > 0.05). Outpatient drain removal after elective lumbar spine surgery was associated with a significantly decreased LOS without a significant increase in postoperative SSI or hematoma. Although the choice of drain removal and the LOS may be subject to surgeons' preference, these results may support the feasibility and safety of outpatient drain removal, and the potential cost savings resulting from shortened hospital stays. Drawbacks may exist regarding added burden to the patient and the surgeon's team to accommodate 1-week follow-up appointments for drain removal.

Retrospective study of the clinical significance of the neutrophil-to-lymphocyte ratio in 79 patients with palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic relapsing inflammatory skin disease characterized by multiple vesicles, pustules, and erythematous plaques on the palms and soles. The exacerbation of PPP is strongly associated with focal infections, such as tonsillitis, dental infections, and sinusitis, in Japan. Recently, the neutrophil-to-lymphocyte ratio (NLR) has been widely used as a convenient and useful marker for clinical conditions and various diseases; however, an association between PPP and NLR has not yet been established. We retrospectively analyzed 79 patients with PPP from our hospital to evaluate the clinical significance of the NLR. The average NLR value in patients with PPP was significantly higher than that in healthy controls (2.30 ± 1.02 vs 1.69 ± 0.45, P < 0.001). A comparative analysis of patients with PPP with and without infectious complications showed that there was a statistical difference in the NLR between patients with PPP with and without focal infections, whereas no significant difference was found for metal allergy, smoking, and pustulotic arthro-osteitis. Multivariate analysis indicated that the NLR was significantly associated with focal infections (odds ratio = 18.38, 95% confidence interval 3.86-87.35, P < 0.001). The NLR was also significantly correlated with C-reactive protein levels (P = 0.013, r = 0.2857). Interestingly, after symptom improvement, the NLR significantly decreased from the baseline levels. Furthermore, statistical analysis using the Youden's index revealed that an NLR of 2.28 or higher was associated with the risk of any focal infections in patients with PPP. These results suggest that the NLR has potential applications as a biomarker of the presence of focal infections in patients with PPP.

Blister formation in acute compartment syndrome: Unraveling the underlying predictors.

Blisters are a common complication of orthopedic trauma and can cause surgery delay and increase the risk of infection. This study aims to identify risk factors for blisters in patients with acute compartment syndrome (ACS). Our study collected data from 206 ACS patients admitted to 2 hospitals between November 2013 and January 2021. Patients were divided into 2 groups: the blister group (BG) and the control group (CG), based on the presence or absence of blisters. We conducted univariate analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis to identify any significant differences in demographics, comorbidities, and admission laboratory test results between the 2 groups. Our study found that the incidence of blisters in ACS patients was 21.8% (45 out of 206). Univariate analysis identified several factors that were significantly associated with blister formation. Logistic regression analysis showed that patients who developed ACS in the winter or spring (P = .007, OR = 2.690, 95% CI [1.308-5.534]), patients who received a referral (the process whereby patients are transferred between medical facilities for further evaluation and treatment attempts prior to admission to our hospital) (P = .009, OR = 4.235, 95% CI [1.432-12.527]), and patients with higher PLR (P = .036, OR = 1.005, 95% CI [1.000-1.009]) were independent risk factors for blisters. Additionally, a history of drinking (P = .039, OR = 0.027, 95% CI [0.046-0.927]) was found to be a protective factor for blister formation in these patients. Moreover, ROC curve analysis showed that a PLR value of 138 was the cutoff point for predicting the development of blisters in ACS patients. Our study identified seasonal factors (refer to these months like winter or spring), referral, and patients with higher PLR as independent risk factors, and a history of drinking as a protective factor for blister formation in ACS patients. These findings allow clinicians to individualize the evaluation of blister risk and perform early targeted therapies.

The penetration phenomenon of the expiratory airflow from thermal plume of human body in the microenvironment around people

Understanding the influence of the human body's thermal plume on exhaled airflow is crucial for accurately assessing indoor infection risks. This study employs numerical simulations and a jet integral modeling method to investigate the airflow dispersion patterns of a single thermal manikin during sustained expiration. It was found that the thermal plume formed a two-stage evolution in exhaled airflow. Initially, the airflow was weakened by the thermal plume in the horizontal dispersion, and subsequently it was bent due to the entrainment of the surrounding air in the upward dispersion of the exhaled airflow. The thermal plume changes the trajectory and lateral dispersion distance of exhaled airflow. When the exhalation velocity is 1 m/s, the airflow is fully deflected towards the head plume region. When the exhalation velocity is between 1.5 and 2 m/s, the airflow is partially deflected, with only part of the upper airflow deflected towards the head plume region. In addition, it is interesting to note that the plume changes the dispersion trajectory of the exhaled airflow, while still adhering to the distributions of buoyant jet flow. This study suggests that the thermal effect of the human body is a significant factor in characterizing the dispersion of exhalation airflow and aerosols. Considering the thermal plume in indoor infection risk assessment is expected to yield more reliable data for theoretical modeling of respiratory airflow transport.

Association of pre-existing depression and anxiety with Omicron variant infection.

Pre-existing psychiatric disorders were linked to an increased susceptibility to COVID-19 during the initial outbreak of the pandemic, while evidence during Omicron prevalence is lacking. Leveraging data from two prospective cohorts in China, we identified incident Omicron infections between January 2023 and April 2023. Participants with a self-reported history or self-rated symptoms of depression or anxiety before the Omicron pandemic were considered the exposed group, whereas the others were considered unexposed. We employed multivariate logistic regression models to examine the association of pre-existing depression or anxiety with the risk of any or severe Omicron infection indexed by medical interventions or severe symptoms. Further, we stratified the analyses by polygenic risk scores (PRSs) for COVID-19 and repeated the analyses using the UK Biobank data. We included 10,802 individuals from the Chinese cohorts (mean age = 51.1 years, 45.6% male), among whom 7841 (72.6%) were identified as cases of Omicron infection. No association was found between any pre-existing depression or anxiety and the overall risk of Omicron infection (odds ratio [OR] =1.04, 95% confidence interval [CI] 0.95-1.14). However, positive associations were noted for severe Omicron infection, either as infections requiring medical interventions (1.26, 1.02-1.54) or with severe symptoms (≥3: 1.73, 1.51-1.97). We obtained comparable estimates when stratified by COVID-19 PRS level. Additionally, using clustering method, we identified eight distinct symptom patterns and found associations between pre-existing depression or anxiety and the patterns characterized by multiple or complex severe symptoms including cough and taste and smell decline (ORs = 1.42-2.35). The results of the UK Biobank analyses corroborated findings of the Chinese cohorts. In conclusion, pre-existing depression and anxiety was not associated with the risk of Omicron infection overall but an elevated risk of severe Omicron infection, supporting the continued efforts on monitoring and possible early intervention in this high-risk population during Omicron prevalence.

Hydrogen Peroxide May Reduce the Risk for Revision Surgery and Infection in Primary Shoulder Arthroplasty: Two-year Follow-up From a Prospective, Blinded, Controlled Trial.

The purpose of this study was to determine whether the addition of hydrogen peroxide to the preoperative skin preparation for primary total shoulder arthroplasty is associated with a difference in patient-reported outcomes, risk for postoperative infection, and risk for revision surgery at a minimum of 2-year follow-up. This was a prospective, blinded, and controlled trial, which included a consecutive series of patients undergoing primary shoulder arthroplasty. The control group underwent standard sterile skin preparation using ethyl alcohol and ChloraPrep applicators, and the peroxide group had the same preparation with the addition of hydrogen peroxide between the alcohol and ChloraPrep applications. We then compared patient-reported outcome scores (American Shoulder and Elbow Surgeons Shoulder Score [ASES], simple shoulder test [SST], visual analog scale [VAS]), infections, and revision surgeries between the two groups at 2-year follow-up. Of the 61 patients included in the original study, 52 of 58 (85%) living patients agreed to participate in this study. No preoperative differences were observed between groups. No difference was observed in ASES, SST, or VAS scores at 2 years. More revision surgeries were done in the control group (7 versus 2, P = 0.268) and Cutibacterium acnes infections (2 versus 0, P = 0.168). The addition of hydrogen peroxide to the preoperative skin preparation before primary shoulder arthroplasty is safe, and additional research is warranted to investigate whether it may decrease the risk for revision surgery and postoperative C acnes infection. III.

Current use of estrogen-containing oral contraceptives or hormone therapy and risk of COVID-19 infection and hospitalization: a population-based cohort study.

This population-based cohort study evaluated the association between current use of oral contraceptives (OC) among women under 50 years (n=306,541), and hormone therapy (HT) among women aged 50 or older (n=323,203), and COVID-19 infection and hospitalization. Current OC/HT use was recorded monthly using prescription dispensing data. COVID-19 infections were identified March 2020-February 2021. COVID-19 infection and hospitalization were identified through diagnosis codes and laboratory tests. Weighted generalized estimating equations models estimated multivariable-adjusted odds ratios (aORs) for COVID-19 infection associated with time-varying OC/HT use. Among women with COVID-19, logistic regression models evaluated OC/HT use and COVID-19 hospitalization. Over 12 months, 11,727 (3.8%) women <50 years and 8,661 (2.7%) women ≥50 years experienced COVID-19 infections. There was no evidence of an association between OC use and infection (aOR=1.05; 95%CI: 0.97, 1.12). There was a modest association between HT use and infection (aOR=1.19; 95%CI: 1.03, 1.38). Women using OC had a 39% lower risk of hospitalization (aOR=0.61; 95%CI: 0.38, 1.00), but there was no association of HT use with hospitalization (aOR=0.89; 95%CI: 0.51, 1.53). These findings do not suggest a meaningfully greater risk of COVID-19 infection associated with OC or HT use. OC use may be associated with lower COVID-19 hospitalization risk.

Implementation of Inpatient Electronic Consultations During the COVID-19 Crisis and Its Sustainability Beyond the Pandemic: Quality Improvement Study.

Limiting in-person contact was a key strategy for controlling the spread of the highly infectious novel coronavirus (COVID-19). To protect patients and staff from the risk of infection while providing continued access to necessary health care services, we implemented a new electronic consultation (e-consult) service that allowed referring providers to receive subspecialty consultations for patients who are hospitalized and do not require in-person evaluation by the specialist. We aimed to assess the impact of implementing e-consults in the inpatient setting to reduce avoidable face-to-face referrals during the COVID-19 pandemic. This quality improvement study evaluated all inpatient e-consults ordered from July 2020 to December 2022 at the University of California Irvine Medical Center. The impact of e-consults was assessed by evaluating use (eg, number of e-consults ordered), e-consult response times, and outcome of the e-consult requests (eg, resolved electronically or converted to the in-person evaluation of patient). There were 1543 inpatient e-consults ordered across 11 participating specialties. A total of 53.5% (n=826) of requests were addressed electronically, without the need for a formal in-person evaluation of the patient. The median time between ordering an e-consult and a specialist documenting recommendations in an e-consult note was 3.7 (IQR 1.3-8.2) hours across all specialties, contrasted with 7.3 (IQR 3.6-22.0) hours when converted to an in-person consult (P<.001). The monthly volume of e-consult requests increased, coinciding with surges of COVID-19 cases in California. After the peaks of the COVID-19 crisis subsided, the use of inpatient e-consults persisted at a rate well above the precrisis levels. An inpatient e-consult service was successfully implemented, resulting in fewer unnecessary face-to-face consultations and significant reductions in the response times for consults requested on patients who are hospitalized and do not require an in-person evaluation. Thus, e-consults provided timely, efficient delivery of inpatient consultation services for appropriate problems while minimizing the risk of direct transmission of the COVID-19 virus between health care providers and patients. The service also demonstrated its value as a tool for effective inpatient care coordination beyond the peaks of the pandemic leading to the sustainability of service and value.

Hypothermia in patients with cardiac arrest prior to ECMO-VA: Insight from the HYPO-ECMO trial.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become a common intervention for patients with cardiogenic shock (CS), often complicated by cardiac arrest (CA). Moderate hypothermia (MH) has shown promise in mitigating ischemia-reperfusion injury following CA. The HYPO-ECMO trial aimed to compare the effect of MH versus normothermia in refractory CS rescued by VA-ECMO. The primary aim of this non-predefined post hoc study was to assess the treatment effect of MH in the subgroup of patients with cardiac arrest (CA) within the HYPO-ECMO trial. Additionally, we will evaluate the prognostic significance of CA in these patients. This post hoc analysis utilized data from the randomized HYPO-ECMO trial conducted across 20 French cardiac shock care centers between October 2016 and July 2019. Participants included intubated patients receiving VA-ECMO for CS for less than 6 hours, with 334 patients completing the trial. Patients were randomized to early MH (33-34°C) or normothermia (36-37°C) for 24 hours. Of the 334 patients, 159 (48%) experienced preceding CA. Mortality in the CA group was 50.9% at 30 days and 59.1% at 180 days, compared to 42.3% and 51.4% in the no-CA group, respectively (adjusted risk difference [RD] at 30 days, 8.1% [-0.8 to 17.1%], p=0.074 and RD at 180 days 7.0% [-3.0 to 16.9%], p=0.17). MH was associated with a significant reduction in primary (RD -13.3% [-16.3 to -0.3%], p=0.031) and secondary outcomes in the CA group only (p<0.025 for all), with a significant interaction between MH and CA status for 180-day mortality [p=0.03]. This post hoc analysis suggests that MH shows potential for reducing mortality and composite endpoints in patients with cardiac arrest and refractory CS treated with VA-ECMO without an increased risk of severe bleeding or infection. Further research is needed to validate these findings and elucidate underlying mechanisms.

Per-and polyfluoroalkyl substances may be correlated with Chlamydia trachomatis: data from NHANES 2003-2016.

Per-and polyfluoroalkyl substances (PFAS) alter immune function increasing infectious diseases risk. We examined the relationship between PFAS and chlamydia. 3,965 non-pregnant adults ages 18-39 years from the National Nutrition Examination Survey (NHANES), 2003-2016 cycles were included. Poisson regression with robust error variance estimated the prevalence ratio and 95% confidence intervals for the association between PFAS and chlamydia. A g computation model was used to examine PFAS mixtures and chlamydia. In adjusted age and sex-stratified models, an increase in PFAS mixtures by one quintile was associated with chlamydia in older males and younger females. Associations were not observed prior to stratification. PFAS exposure associated with higher chlamydia prevalence, but only in stratified models suggesting biological differences by gender and age. Although small sample sizes could have affected the precision of our models.

In vitro mimicry of in vivo KPC mutations by ceftazidime-avibactam: phenotypes, mechanisms, genetic structure and kinetics of enzymatic hydrolysis

Ceftazidime-avibactam (CZA) is employed for the treatment of infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP). Resistance to CZA is frequently linked to point mutations in the bla KPC. We conducted in vitro simulations of in vivo bla KPC mutations using CZA. Four pre-therapy KPC-KP isolates (K1, K2, K3, and K4) were evaluated, all initially exhibited susceptibility to CZA and produced KPC-2. The crucial distinction was that following CZA treatment, the bla KPC-2 mutated in K1, K2, and K3, rendering them resistant to CZA, while K4 achieved microbiological clearance, and bla KPC-2 remained unaltered. The induction assay identified various bla KPC-2 variants, including bla KPC-25, bla KPC-127, bla KPC-100, bla KPC-128, bla KPC-137, bla KPC-138, bla KPC-144 and bla KPC-180. Our findings suggest that the resistance of KPC-KP to CZA primarily results from the emergence of KPC variants, complemented by increased bla KPC expression. A close correlation exists between avibactam concentration and the rate of increased CZA minimum Inhibitory concentration, as well as bla KPC mutation. Inadequate avibactam concentration is more likely to induce resistance in strains against CZA, there is also a higher likelihood of mutation in the bla KPC-2 and the optimal avibactam ratio remains to be determined. Simultaneously, we selected a bla KPC-33-producing K. pneumoniae strain (mutated from bla KPC-2) and induced it with imipenem and meropenem, respectively. The bla KPC-2 was detected during the process, indicating that the mutation is reversible. Clinical use of carbapenems to treat KPC variant strains increases the risk of infection, as the gene can mutate back to bla KPC-2, rendering the strain even more cross-resistant to carbapenems and CZA.

Targeted complement inhibition using bispecific antibodies that bind local antigens and endogenous complement regulators

Complement activation protects against infection but also contributes to pathological mechanisms in a range of clinical conditions such as autoimmune diseases and transplant rejection. Complement-inhibitory drugs, either approved or in development, usually act systemically, thereby increasing the risk for infections. We therefore envisioned a novel class of bispecific antibodies (bsAbs) which are capable of site-directed complement inhibition by bringing endogenous complement regulators in the vicinity of defined cell surface antigens. Here, we analyzed a comprehensive set of obligate bsAbs designed to crosslink a specific target with either complement regulator factor H (FH) or C4b-binding protein (C4BP). The bsAbs were assessed for their capacity to inhibit complement activation and cell lysis in an antigen-targeted manner. We observed that the bsAbs inhibited classical, lectin, and alternative pathway complement activation in which sufficient endogenous serum FH and C4BP could be recruited to achieve local inhibition. Importantly, the bsAbs effectively protected antigen-positive liposomes, erythrocytes, and human leukocytes from complement-mediated lysis. In conclusion, localized complement inhibition by bsAbs capable of recruiting endogenous human complement regulators (such as FH or C4BP) to cell surfaces potentially provides a novel therapeutic approach for the targeted treatment of complement-mediated diseases.

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

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 robotic assisted laparoscopic radical prostatectomy (RALP). We explored the feasibility of immediate RALP in men with PIRADS 5 lesions without preceding biopsy. After obtaining institutional review board approval, a prospective analysis was conducted on 235 patients with PIRADS 5 on mpMRI from December 2018 to February 2023. Patients were divided into 2 groups: Group NoBiopsy (biopsy not done before RALP, cases, n=118) and Group YesBiopsy (biopsy done before RALP, controls, n=117). Baseline pre-operative, intra-operative and post-operative 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. 95% 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, pre-operative 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 to 88% of men in Group YesBiopsy (p < 0.04). All men in the study cohort were continent (0 pads) at 12 months post-RALP. 98% 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. RALP without antecedent prostate biopsy in men with PIRADS 5 lesions demonstrated substantial csPCa detection rates and superior functional outcomes, warranting further validation.

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials.

Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Changing risk factors for developing SARS-CoV-2 infection from Delta to Omicron.

One of the few studies to estimate infection risk with SARS-CoV-2 in the general population was the UK Office of National Statistics Infection Survey. This survey provided data that allowed us to describe and interpret apparent risk factors for testing positive for SARS-CoV-2 in a period when variants and COVID-19 controls experienced large changes. The ONS published estimates of likelihood of individuals testing positive in two week monitoring periods between 21st November 2021 and 7th May 2022, relating this positivity to social and behavioural factors. We applied meta-regression to these estimates of likelihood of testing positive to determine whether the monitored potential risk factors remained constant during the pandemic. Some risk factors had consistent relationship with risk of infection (always protective or always linked to higher risk, throughout monitoring period). Other risk factors had variable relationship with risk of infection, with changes seeming to especially correlate with the emergence of Omicron BA.2 dominance. These variable factors were mask-wearing habits, history of foreign travel, household size, working status (retired or not) and contact with children or persons age over 70. Relevance of some risk factors to likelihood of testing positive for SARS-CoV-2 may relate to reinfection risk, variant infectiousness and status of social distancing regulations.