Urinary Tract Infection Research Articles

Programmed DNA tile response system enabled accurate detection of ATP for clinical diagnosis

Adenosine triphosphate (ATP), as a crucial signaling molecule, is of high potential diagnosis value for multiple diseases. However, current technologies for ATP detection struggle to satisfy the harsh conditions required for biospecimen tests, existing several limitations for clinical practical application. In this study, the DNA tile response system was designed and constructed by integrating nucleic acid aptamer, hybrid chain reaction (HCR), and DNA tile self-assembly technology to achieve accurate detection of ATP in body fluid specimens. The DNA tile response system, possessing high-order structure characteristic, could remove HCR false-positive products and conquer the high noise background to enhance the detection sensitivity. Under the optimal reaction parameters, this system achieved the low limit of detection (LOD) of 189.23 nM over a wide linear range and splendid detection specificity faced with multiple interference terms. Furthermore, this system, possessing simple storage conditions, long-term detection stability, and superior anti-interference performance, was sufficient to satisfy the detection requirements for complicated biological specimens in multi-scenarios. Ultimately, the DNA tile response system showed excellent diagnostic efficiency that could easily distinguish urinary tract infection patients and healthy controls through ATP quantification, as well as hypertension patients and healthy ones. This system provides a high-potential rapid detection tool for early diagnosis and dynamic monitoring of urinary tract infections and hypertension, holding enormous potential for clinical translation due to the superiorities of simple operation, general applicability, and low instrument requirements.

Comparing costs associated with management of antibiotic-recalcitrant recurrent urinary tract infections for one year pre- and post-electrofulguration.

To quantify and compare recurrent urinary tract infection costs between 1 year before and 1 year after electrofulguration. Following IRB approval, a well-characterized cohort of non-neurogenic women with >3 symptomatic urinary tract infections(UTIs)/year, a negative upper and lower urinary tract evaluation, and inflammatory bladder lesions (cystitis) on office cystoscopy who underwent fulguration of these lesions was analyzed. Cost of visits, imaging, labs, and medications were summed for 1-year pre- and post-fulguration using the Medicare Physician Fee Schedule, local pharmacy pricing, and institutional expenses. Before fulguration, all patients underwent clinic visit, noninvasive flow study, and flexible cystoscopy, and post-fulguration, 6-week follow-up visit and 6-month cystoscopy. Ninety-threewomen met study criteria (mean age 64), with 100% 1-year follow-up. Before fulguration, 73% of patients used daily antibiotic suppression, 6% self-start antibiotics, and 5% postcoital prophylaxis. Some also used vaginal estrogens (17%), urinary analgesics (13%), and cranberry or d-mannose supplements (7%). At 1 year post-fulguration, 82% had 0-1 infections and no cystoscopy evidence of cystitis, while 14% required additional fulguration for new cystitis sites and recurrent infections. Patients had on average 0.7 infections in the 1-year post-fulguration, which was significantly lower than pre-fulguration (p < 0.05). Mean 1-year pre-fulguration cost was $1328 (median $1071, range $291-$5564). Mean 1-year post-fulguration cost was $617 (median $467, range $275-$4580). On average, post-fulguration costs were $710 lower than pre-EF (p < 0.05). For women with antibiotic-refractory recurrent urinary tract infections and cystoscopy evidence of cystitis, fulguration was associated with a significant reduction in UTI-related costs in the 1-year post-fulguration.

Transition metals tailoring of phosphorus-doped gallium nitride nanotubes as sensors for N-butenyl homoserine lactone (BHL): A computational study

This investigation is focused on the impact of transition metals (Ag, Au, and Cu) encapsulations of phosphorus-doped gallium nitride nanotubes (P@GaNNTs) to achieve precise detection and sensing of N-Butenyl homoserine lactone (BHL), which is a biomarker for urinary tract infection, within the framework of density functional theory (DFT) computation at the B3LYP-D3(BJ)/def2SVP method. Adsorption studies unveil the adsorption energies for BHL detection across the systems, with BHL_Cu_P@GaNNT displaying the most favorable adsorption energy of −1.79247 eV and BSSE correction (−1.7685 eV). Additionally, sensor mechanisms are elucidated through Fermi energy level (EFL) calculations, revealing distinct values of 4.748, 4.242, 5.052, and 3.864 for BHL_Ag_P@GaNNT, BHL_Au_P@GaNNT, BHL_Cu_P@GaNNT, and BHL_P@GaNNT, respectively. These values signify variances in charge transfer dynamics upon BHL interaction. In essence, this study lays the foundation for the development of highly efficient biosensors with exceptional biomarker detection capabilities, particularly in the context of urinary tract infections (UTIs). It opens new avenues in the realm of biosensing technology, promising innovative solutions for healthcare and diagnostics.

Changes in Secondary Health Conditions Among Individuals With Spinal Cord Injury After Transition From Inpatient Rehabilitation to Community Living.

The aim of the study is to examine the changes in the burden of secondary health conditions and their risk factors among newly injured individuals with spinal cord injury after discharge from inpatient rehabilitation to community living. This is a prospective cohort study. Among 280 included persons, the majority were men with traumatic spinal cord injury and paraplegia. The most common secondary health conditions at discharge from rehabilitation and in the community setting were pain (60.8% vs. 75.9%), urinary tract infections (27.8% vs. 47.6%), and pressure sores (9.9% vs. 27.5%). There was also a significant increase in reported heart disease (9.3% vs. 14.8%) and diabetes (0% vs. 4.2%). The odds of experiencing pain, pressure sores, depression and urinary tract infections increased after discharge from rehabilitation, whereas the odds of respiratory problems decreased significantly during the observation period. Factors such as sex, injury severity, activity limitations, and duration of follow-up were identified as potential risk factors influencing secondary health condition occurrence. Our study emphasizes a significant rise in secondary health conditions after the transition to community living. Future research should prioritize development of targeted intervention programs tailored to address the unique needs of affected individuals at this pivotal stage in the continuum of spinal cord injury care.

Investigation of Nosocomial Urinary Tract Infections Post Transplantation, Main Pathogens, and Sensitivity Tests

Background: Regarding end-stage organ disease, transplantation is recommended as the best therapeutic management. After organ transplantation, the incidence of nosocomial urinary tract infections (NUTIs) due to multidrug-resistant Gram-negative bacilli increases. Aim: The study aimed to investigate NUTIs post-transplantation, the main pathogens involved, and sensitivity tests conducted in a tertiary hospital in Isfahan, Iran. Methods: A retrospective survey on patients admitted to a tertiary hospital in Isfahan (Alzahra), Iran, was performed between 27 March, 2017, and 9 February, 2022. The information recorded included the date of infection, date of hospitalization, gender, age, type of pathogens, and resistance or sensitivity to antibiotics. Results: 73 kidney transplant recipients (61% females) with a mean age of 43. 2 ± 15.1 years were included. Within this population involving both genders, the main pathogens involved in NUTIs were as follows: Escherichia coli (30%), Klebsiella pneumonia (19%), Candida albicans and non-albicans (14%), Enterococcus faecalis (12%), Enterobacteriaceae (8%), Pseudomonas aeruginosa (6%), Staphylococcus spp. (6%), Acinetobacter baumannii (4%), and Streptococcus spp. (4%). Antibiotic susceptibility testing showed the most sensitivity of isolates against amikacin (n=29; 66%), meropenem (n= 28; 64%), piperacillin/tazobactam (n=26; 54%), cefepime (n= 25; 40%), ceftazidime (n= 27; 30%), ciprofloxacin (n= 40; 18%), and co-trimoxazole (n= 29; 10%). Conclusion: Escherichia coli, Klebsiella pneumonia, and Candida spp. were the major causes of NUTIs within the studied organ-transplanted recipients. Amikacin, meropenem, and piperacillin/ tazobactam have shown more than 50% sensitivity against isolates. Further evidence-based pharmacotherapy investigations associated with the different spectrum antibiotics and overall antimicrobial success rate is recommended to be advantageous.

Efficacy and safety of onabotulinumtoxinA for the treatment of overactive bladder in men and women: A pooled analysis.

This pooled analysis of randomized controlled studies investigated the safety and efficacy of onabotulinumtoxinA in male and female patients with overactive bladder (OAB). Data were pooled from four similarly designed trials in North America and Europe. Adults with idiopathic OAB for ≥6 months inadequately managed by at least one anticholinergic were randomized 1:1 or 2:1 to receive onabotulinumtoxinA 100 U or matched placebo in Cycle 1 and could request open-label retreatment with onabotulinumtoxinA 100 U at ≥12 weeks. Efficacy outcomes at Week 12 included the primary endpoint of mean urinary incontinence (UI) episodes per day and other variables, such as the proportion of patients with ≥50% reduction in daily UI episodes. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs). Analyses by sex were descriptive. Males were further analyzed by benign prostatic hyperplasia (BPH) diagnosis status. In the pooled population (N = 1564), there were 194 males (12.4%) and 1370 females (87.6%). Mean number of baseline UI episodes per day was 4.9 in males and 5.5 in females. At Week 12, numerically greater mean reductions from baseline in number of daily UI episodes were observed with the onabotulinumtoxinA 100 U group (females: -3.0; males: -2.2) versus placebo (females: -1.1; males: -1.3). Achievement of ≥50% reduction in daily UI episodes was numerically greater with onabotulinumtoxinA 100 U (females: 64.8%; males: 61.2%) versus placebo (females: 30.6%; males: 44.8%), and numerically higher in males without BPH (onabotulinumtoxinA: 65.1%; placebo: 50.9%) versus with BPH (onabotulinumtoxinA: 54.3%; placebo: 36.6%). A total of 34.7% of males and 39.4% of females experienced at least one TEAE in the first 12 weeks during treatment Cycle 1. Urinary tract infection rate was 13.1% in females and 4.2% in males; incidence of hematuria was 6.8% in males and 1.1% in females. Incidence of urinary retention (defined as incomplete emptying, requiring catheterization) was 2.7% in females and 4.7% in males. OnabotulinumtoxinA 100 U was efficacious and well tolerated in men and women with OAB, including in males with and without BPH. No new safety findings were identified when data were analyzed by sex.

Misuse of External Urine Management Devices in Hospitalized Patients.

External urine management devices were introduced into healthcare as a novel solution to avoid indwelling urinary catheter placement and the associated urinary tract infection risk for adult patients. These devices are favored among healthcare workers and patients. However, the downstream impacts of this device can be detrimental to patient outcomes when immobility is promoted through their use. Clinical nurse specialists are the ideal team member to evaluate the introduction of new technology to promote patient-focused care over task-focused care.

Antibiotic profile classification of Proteus mirabilis using Machine Learning: An Investigation into Multidimensional Radiomics Features

Antimicrobial resistance (AMR) presents a significant threat to global healthcare. Proteus mirabilis causes catheter-associated urinary tract infections (CAUTIs) and exhibits increased antibiotic resistance. Traditional diagnostics still rely on culture-based approaches, which remain time-consuming. Here, we study the use of machine learning (ML) to classify bacterial resistance profiles using straightforward microscopic imaging of P. mirabilis for resistance classification integrated with radiomics feature analysis and ML models.From 150 P. mirabilis strains isolated from catheters of patients diagnosed with a CAUTI, 30 % displayed multidrug resistance using the standardized disk diffusion method, and 60% showed strong biofilm activity in microtiter plate assays. As a more rapid alternative, we introduce wavelet-based and regular microscopy imaging with feature extraction/selection, following image preprocessing steps (image denoising, normalization, and mask creation). These features enable training and testing different ML models with 5-fold cross-validation for P. mirabilis resistance classification. From these models, the Random Forest (RF) algorithm exhibited the highest performance with ACC=0.95, specificity=0.97, sensitivity=0.88, and AUC=0.98 among the other ML algorithms considered in this study for P. mirabilis resistance classification.This successful application of wavelet-based feature Radiomics analysis with RF model represents a crucial step towards a precise, rapid, and cost-effective method to distinguish antibiotic resistant P. mirabilis strains.

Detection of the antibacterial role of Achillea millefolium against Escherichia coli isolated from urinary tract infections

Despite the fact that the pharmaceutical industry has developed numerous novel antibiotics over the last three decades, bacteria have developed resistance to these medications. Bacteria have the genetic potential to transfer and develop resistance to medications used as therapeutic agents. Therefore, the present study aimed to reveal the antibacterial role of Achillea millefolium against Escherichia coli isolated from urinary tract infections. Between February and July of 2024, 130 clinical samples were taken from individuals who were admitted to Kirkuk Hospital in Kirkuk City after visiting a specialist and being sent to the laboratory. Urine samples were taken from patients with UTI ranging in age from (1-60 years) of women, after which they were transferred directly to the laboratory to be cultured on the culture media, then A. millefolium extract was tested against Escherichia coli, compared with some standard antibiotics. Results showed that 57 (43.8%) of the total samples showed positive results for bacterial growth when cultured on the best culture media, which included blood and MacConkey agars. 73 (or 56.2%) of the total samples had results that showed no bacterial growth. E. coli showed total resistance (100%) to Ampicillin. While, a low sensitive toward Nalidixic acid (20.0%), Clindamycin (20.0%) 21.5%. Otherwise, E. coli showed a high sensitive to Gentamycin (87.7%), Imipenem (96.9%), and Amikacin (90.8%). While Tobromycin showed high sensitive 100.0% respectively. Based on the results, it was shown that the extract of A. millefolium at a dosage of 100 mg induced an inhibition diameter rate of 18.7±3.45, while at a concentration of 150 mg, it produced an inhibition diameter rate of 29.49±2.97. It is concluded from that the alcoholic extract of A. millefolium has an antibacterial effect and is very effective in treating cases of urinary tract infection resulting from infection with Escherichia coli.

Advancing prostate cancer detection: High-accuracy urine test distinguishes between high and low-risk cancers

Prostate cancer remains one of the leading causes of cancer-related deaths among men. The standard method for early detection involves measuring Prostate-specific antigen (PSA) levels in the blood, with elevated PSA levels prompting further diagnostic procedures, such as a prostate biopsy. While effective, biopsies can be painful and carry risks of complications such as fever and urinary tract infections. To reduce unnecessary biopsies, researchers have sought alternative diagnostic methods. In recent years, a urine test was developed for early-stage prostate cancer detection. However, this test struggled to differentiate between aggressive and slow-growing cancers, the latter of which often require minimal treatment and are managed through active surveillance. To address this limitation, scientists at Wunderkind University have significantly enhanced the urine test. By analysing the genomes of thousands of prostate cancer patients, they identified a panel of 16 genes detectable in urine that can effectively distinguish between high-risk and low-risk cancers. When applied to individuals with elevated PSA levels, this improved test demonstrated an impressive 97% accuracy in identifying advanced prostate cancer. This advancement holds great promise for reducing unnecessary biopsies and improving patient outcomes by accurately identifying those needing aggressive treatment versus those suitable for observation. This review paper will explore the development, validation, and clinical implications of this novel urine test, highlighting its potential to transform prostate cancer diagnostics and patient management.

Risk of collagen-related disorders and neurological events among patients with uncomplicated urinary tract infection following short treatment with fluoroquinolones: a cohort study.

Studies of fluoroquinolone (FQ) safety across indications show increased collagen/neurological adverse event (AE) risk, yet patients still receive FQs for uncomplicated urinary tract infections (uUTIs). This retrospective, cohort study investigated the risk of collagen/neurological AEs of special interest (AESIs) with short-term FQ use versus standard-of-care antibiotics (trimethoprim-sulfamethoxazole [SXT], nitrofurantoin [NTF]) among female outpatients with uUTIs. This study was conducted between December 2009 and 2019 using Optum's de-identified Clinformatics Data Mart Database. Adjusted absolute risks were calculated for composite/collagen/neurological AESIs (Kaplan-Meier cumulative hazards, after applying stabilized inverse probability of treatment weighting [sIPTW]). Adjusted hazard ratios were generated (sIPTW Cox proportional hazard modeling). Overall, 954,777 patients were included: FQ (n = 386,537 [40.5%]); SXT (n = 237,120 [24.8%]); NTF (n = 314,585 [32.9%]). Adjusted absolute risk range for collagen/neurological AESIs was <1%-4.5%. The hazard (95% CI) of tendon rupture was 25% higher with FQ versus SXT (1.25 [1.00-1.57]; P = 0.0497). Patients receiving FQ had lower hazard of neurological (0.95 [0.93-0.97]; P < 0.0001), central nervous system (0.85 [0.80-0.89]; P < 0.0001), and peripheral nervous system (0.96 [0.93-0.98]; P = 0.0016) AESIs versus NTF. Following a short treatment duration, FQs were associated with increased risk of tendon rupture versus SXT and reduced risk (adjusted hazard ratios) of neurological AESI versus NTF. Individual patient risk and consequences for known uncommon, yet serious, AEs need to inform appropriate antibiotic choice in treating uUTIs. Patient profile, efficacy, microbiome impact, safety, and surveillance should inform antibiotic selection for uUTI management, in accordance with guidelines.

Novel plasmid-mediated CMY variant (CMY-192) conferring ceftazidime-avibactam resistance in multidrug-resistant Escherichia coli.

The rapid rise of multidrug resistance (MDR) among Gram-negative bacteria has accelerated the development of novel therapies. Ceftazidime-avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor recently approved for the treatment of limited infectious diseases. Here, we describe a novel CMY variant, CMY-192, that confers high-level resistance to CZA. This gene was detected in a clinical MDR Escherichia coli strain (Ec73552) isolated from an outpatient with a community-acquired urinary tract infection who had not received prior CZA treatment. Ec73552 was typed as O101:H9-ST10, a high-risk clone associated with human and animal diseases. Ec73552 was able to colonize the bladder in a mouse model, suggesting that this strain was uropathogenic. CMY-192 shared the highest amino acid identity (98.95%) with CMY-172 and conferred at least a 32-fold increase in CZA MIC (from ≤0.125/4 to 8/4 mg/L) when cloned into a CZA-susceptible E. coli DH5α strain. Knockout of CMY-192 in Ec73552 resulted in a 256-fold reduction in CZA MIC (from 64/4 to 0.25/4 mg/L). CMY-192 was encoded on an IncB/O/K/Z-type plasmid (pCMY192). Conjugation assays confirmed that pCMY192 was self-transmissible, resulting in a 256-fold increase in the CZA MIC of the recipient. Notably, pCMY192 cured in Ec73552 did not confer a growth advantage, while the conjugant exhibited reduced biomass and growth rate, indicating that fitness costs imposed by pCMY192 may have been compensated in Ec73552. Our findings highlight the importance of continuous monitoring of CZA susceptibility to prevent the spread of resistance in clinical settings.

Knowledge and Preventive Practice of Urinary Tract Infection among Bangladeshi Female Ready-made Garments Worker

Ready-made garments (RMG) are Bangladesh’s largest export earner sector, with 800,000 workers, including two-thirds of females. Female RMG workers suffer from various illnesses, including urinary tract infections (UTI), but data is scars related it in Bangladesh. Therefore, the study aimed to evaluate the knowledge and preventive practice of UTI among female RMG workers. Method: This cross-section survey was conducted to evaluate the knowledge and preventive practice of UTI among female RMG workers. Using convenient sampling technique, we collected 351 data between February to April 2021 from two RMG. Data were analysed by using Statistical Package Social Science (SPSS) software version 23. Descriptive statistics was conducted using frequencies and proportions. Chi-square test was used to determine the association between dependent and independent variables. Linear regression and Pearson co-relation was used to determine the association between knowledge and practice. Results: Of 351 participants, 22% had good knowledge and 33% were in good practice. The study found a statistically significant correlation between knowledge level of UTI and participants’ age, education, residence, family size, parents’ education and occupation (p&lt;0.05). Similarly, participants’ education, marital status, residence, family size, parents’ education and occupation were significantly correlated with practice level of female RMG workers towards UTI (p&lt;0.05). Furthermore, participants who received health-related training had good knowledge and practice of UTI. Conclusion: Female RMG workers’ sociodemographic variables were significantly correlated with their knowledge and practice of UTI. Training on health-related issues was significantly associated with good knowledge and practice of UTI. It’s urgent to keep female RMG workers aware of health-related issues and easily accessible health care. EWMCJ Vol. 12, No. 1&amp;2, January-July 2024: 50-59

Functional Outcomes After Decompressive Surgery in Patients with Malignant Space-Occupying Cerebellar Infarction

Background and Purpose: Decompressive surgery is a potentially life-saving treatment in patients with malignant space-occupying cerebellar infarction. However, there is only limited literature on functional outcomes and complications after surgery. Our aim was to establish markers which predict poor outcome. Methods: We retrospectively analyzed data of all patients who underwent surgery due to malignant swelling of a space-occupying cerebellar infarction in our hospital between 2005 and 2023. Statistical analyses were conducted on multiple parameters to identify predictors of poor functional outcome (mRS 4–6) 90 days after surgery. Complications during hospitalization were reviewed for each patient. Results: In total, 58 patients received decompressive surgery. The 90-day mortality rate was 27.6% (n = 16). A good functional outcome (mRS 0–3) 90 days after surgery was achieved in 24 patients (41.4%). Multivariable analysis revealed multiple factors associated with a poor outcome on day 90 (mRS 4–6): a higher premorbid mRS score (OR 2.715 [95% CI, 1.166–6.323]; p = 0.021), higher NIHSS score on admission (OR 1.088 [95% CI, 1.014, 1.168]; p = 0.019) and the presence of an additional brainstem infarction (OR 7.035, [95% CI, 1.255, 39.424], p = 0.027). Hyperactive delirium was associated with good clinical outcome (OR 0.020 [95%CI, 0.001–0.623]; p = 0.026). Aspiration pneumonia (n = 22, 37.9%), urinary tract infection (n = 15, 25.9%), and hyperactive delirium (n = 8, 13.8%) were the most common complications during hospitalization. Conclusions: Decompressive surgery is a safe, life-saving treatment for malignant space-occupying cerebellar infarction. Higher premorbid mRS, higher NIHSS score on admission and the presence of brainstem infarction are associated with a poor functional outcome.

Do the prevention procedures work in reducing infections?

Abstract Introduction Healthcare-associated infections (HCAIs) pose significant challenges in healthcare settings. Poor environmental hygiene contributes to HCAI. This study aims to evaluate and to assess the effectiveness of HCAI containment practices in nursing homes (NH). Methods The study examined infection prevention procedures in eight NHs supervised by the Multidisciplinary Commission of the Tuscany South-East Local Health Authority of Italy. Infection frequencies were obtained from NHs management and compliance with preventive procedures was assessed by inspection reports. Infection prevention protocols, including cleaning and disinfection procedures, were referenced from ministerial guidelines for hospital and territorial facilities. Comparisons was done whit Mann-Whitney test, using STATA. Results In 2023 more frequent infections were SARS-CoV-2 (19.5%), urinary tract infections (17%), pharyngitis (15.7%), influenza-like syndromes (ILI) (15%), and pneumonia (9%). Compared to 2022, significant improvements were observed in legionellosis surveillance, laundry, sanitary procedures, instrument disinfection, and hairdressing services. Non-compliance to specific procedures revealed differences in infectious onset like cleaning process verification with fungal infections (P = 0.01; M = 2,5), gastrointestinal infections (P = 0.04; M = 1.5); cleaning sanitary pans with Clostridium Difficile gastrointestinal infections (P = 0.04; M = 2); instrument disinfection with gastrointestinal infections (P = 0.04; M = 1.5) conjunctivitis (P = 0.01; M = 8); laundry procedures with pneumonia (P = 0.04; M = 18) and ILI (P = 0.04; M = 35). Conclusions These findings emphasize the importance of well-defined procedures in reducing HCAIs. While preventive measures demonstrate efficacy, continuous efforts are necessary for their consistent implementation. Continuous monitoring and stakeholder engagement are essential for developing sustainable strategies in preventing healthcare-associated infections. Key messages • Healthcare-associated infections are a significant complication in the healthcare sector and require effective practices in nursing homes. • Prevention measures are effective, but continuous and collaborative effort is needed to ensure their uniform implementation and develop more effective strategies in preventing HCAI.

First trimester maternal infections and offspring congenital heart defects: a systematic review and meta-analysis

Abstract Background Maternal infections early in pregnancy have been proposed as playing a role in the development of congenital heart defects. We aimed to summarise contemporary evidence regarding the association between first-trimester maternal infection and risk of offspring congenital heart defects. Methods For this systematic review and meta-analysis, we searched Medline and Embase for studies reporting associations of at least one measure of maternal infection during pregnancy and offspring congenital heart disease in humans and published in English between January 1, 1990 and February 13, 2024. Studies were eligible for inclusion if they reported rates of offspring congenital heart defects among both infected and non-infected mothers, and included a minimum of 50 offspring with congenital heart defects. We stratified associations by type of infection and type of heart defect when data from at least two studies were available. We used inverse variance weighted random-effect meta-analyses to pool the estimates. In main analyses, we pooled crude estimates from studies reporting maternal infections during the first trimester of pregnancy. We performed sensitivity analyses to include studies that i) investigated infections later in pregnancy or at unspecified time-points, and ii) adjusted for potential confounders such as maternal age, socioeconomic status, or ethnicity. Findings: We identified 11 studies (7 case control studies, 4 cohort studies) with data from 1,805,115 pregnancies. Nine of these studies assessed maternal infectious status through self-reported questionnaires or medical records, two used laboratory antibody testing and three reported on specific infectious pathogens. Studies reported on various types of bacterial and viral infections, including influenza, urinary tract infections, cytomegalovirus, herpes simplex virus, or chlamydia, with varying effect sizes. Ten studies reported a positive association between maternal infection variables and offspring congenital heart defects, with a pooled odds ratio (OR) and 95% confidence interval of 1.56 (1.27, 1.91) across all types of infections. Associations differed by individual subtype of congenital heart defects, with ORs ranging from 1.28 (0.89, 1.85) for pulmonary atresia to 1.75 (1.23, 2.49) for ventricular septal defects. Sensitivity analyses that included infections measured later in pregnancy, or adjusted rates for potential confounders, showed broadly similar trends but attenuated effect sizes. Interpretation: First trimester maternal infections are associated with increased risk of congenital heart defects. Associations appear to vary by type of infection and type of congenital heart defect, and to extend beyond infections commonly tested for during routine pregnancy screening. Larger-scale studies are warranted to confirm these findings using laboratory antibody testing and investigating how these associations vary by specific pathogens and subtypes of congenital heart defects.

Real-life data on the tolerability of SGLT2 inhibitors in elderly patients with heart failure

Abstract Introduction Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated their effectiveness in improving the prognosis of heart failure. However, there is some hesitation in clinical practice to prescribe them to elderly patients due to a lack of long-term safety data. The SafeGLT2 study aims to evaluate the tolerance of SGLT2i in elderly patients with heart failure in real-life settings. Methods This is a prospective study conducted in acute geriatric units in the Île-de-France region between February 2020 and May 2023. All patients admitted for acute heart failure (AHF), aged 75 years and older, were included. The diagnosis was confirmed by an expert committee, and patients were followed for one year. Treatments were recorded upon admission and discharge, along with demographic characteristics and medical history. SGLT2i tolerance data were collected and analyzed, including renal insufficiency, hypovolemia, genital infections, urinary infections, hypoglycemia, diabetic ketoacidosis, fractures, amputations, etc. A comparison of tolerance data between heart failure patients treated with SGLT2i and those not receiving SGLT2i was performed. Results 288 patients were included in the study with a mean age of 88 years, 53% (n=153) were female, and a median Charlson Comorbidity Index (CCI) of 8.77 [2.71]. 44.1% (n=127) of patients had neurocognitive disorders, 39.6% (n=114) were malnourished, 32.6% (n=94) were fallers, 53.8% (n=155) had renal insufficiency (eGFR &amp;lt; 60 ml/min), and 11.5% (n=33) lived in institutions. A total of 33% (n=95) were treated with SGLT2i upon discharge. No serious adverse effects were found in this very frail population receiving SGLT2i compared to the group not receiving SGLT2i (severe hypotension, hypovolemia, ketoacidosis, hypoglycemia, fracture, amputation). Beneficial effects on renal function (improvement of renal function at 6 months) were observed in the SGLT2i group despite a temporary decrease in glomerular filtration rate of less than 30% after SGLT2i initiation. However, a statistically significant increase in urinary tract infections (16.8% vs 4.15%), genital infections (12.6% vs 1.5%), and constipation (10% vs 1%) was found in the SGLT2i group compared to the group without SGLT2i. Conclusion These data indicate that SGLT2i are well tolerated in very elderly frail heart failure patients. However, the occurrence of urogenital infections appears to be more frequent in this population and requires particular surveillance.

Risks of incident genitourinary malignancies in anticoagulated atrial fibrillation patients experiencing hematuria

Abstract Background When managing oral anticoagulant (OAC)-related bleeding in patients with atrial fibrillation (AF), the possibility of occult malignancies should be kept in mind, as suggested by guidelines. In this study, we aimed to investigate the incidence of genitourinary (GU) trat cancer in anticoagulated AF patients experiencing hematuria. Also, we aimed to report the prevalence of other causes of hematuria beside malignancy. Methods We conducted a nationwide, retrospective cohort study in Taiwan. A total of 19,974 AF patients aged ≥ 20 years on OAC treatment (warfarin 9232, non-vitamin K antagonist OACs [NOACs] 10,742) experiencing hematuria were enrolled. Risk of newly diagnosed GU malignancy within one year after hematuria was reported and compared between patients receiving warfarin and NOACs. Results A total of 738 patients (3.99%) were diagnosed to have GU tract cancers within 1 year after OAC-related hematuria, with prostate cancer (52.30%) being as the commonest subtype, followed by bladder cancer (31.71%) and kidney/ureter/urethra in origin (15.99%)(Figure 1). The risk of GU tract cancer was higher for warfarin compared to NOAC users (4.10% versus 3.89%; odds ratio 1.169, p = 0.041)(Figure 1). For patients without diagnosed GU tract cancers, urinary tract infection (42.3%) was the leading cause of hematuria followed by benign prostate hyperplasia (37.6%), GU tract stone (16.7) and cystitis (9.2%)(Figure 2). Overall, 27.5% of patients whose causes of hematuria could not be identified (Figure 2). Conclusions Incident GU cancers were diagnosed in 1 of 25 AF patients at 1 year after OAC-related hematuria. Detailed examinations for occult GU cancers and other etiologies are necessary.

Micropercutaneous nephrostomy for intervention in acute upper urinary tract calculi obstruction with hydronephrosis and infection

To compare the efficacy and advantages of mini percutaneous nephrostomy (MPCN), micropercutaneous nephrostomy (MicroPCN), and retrograde ureteric stenting (RUS) in the treatment of acute upper urinary tract calculi (UUTC) obstruction with hydronephrosis and infection, and verify the safety and indications of clinical application of micropercutaneous nephrostomy. Clinical-epidemiological data of patients with acute upper urinary tract calculi obstruction and infection treated in Ningbo No.2 hospital were retrospectively collected from May 2019 to May 2023. 64 patients (20 patients in MPCN group, 13 patients in MicroPCN group, and 31 patients in RUS group) were eligible for analysis based on inclusion and exclusion criteria. P value < 0.05 was considered statistically significant. There were no significant differences in peri-intervention temperature, multiple infection indicators and complications among the three groups. The nutritional status and peri-intervention coagulation function of patients in MicroPCN and RUS groups were poor, the CRP and proportion of using carbapenem advanced antibiotics were higher. The length of hospital stay and the length of hospital stay after the intervention in MPCN and MicroPCN groups were longer, the length and width of calculi were larger, and the degree of hydronephrosis was heavier. Patients in the MicroPCN group had the worst general condition, the lowest hemoglobin before intervention, the longest withdrawal time of vasoactive drugs. MPCN, MicroPCN, and RUS are safe and effective in relieving acute upper urinary tract calculi obstruction complicated with infection. MicroPCN has more advantages for patients with critical illness or complex obstruction urinary lithiasis.

Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking. Purpose Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. Methods TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis &amp;lt; 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. Results Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported. Conclusions SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.