Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria.

Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health.

standR: spatial transcriptomic analysis for GeoMx DSP data.

To gain a better understanding of the complexity of gene expression in normal and diseased tissues it is important to account for the spatial context and identity of cells in situ. State-of-the-art spatial profiling technologies, such as the Nanostring GeoMx Digital Spatial Profiler (DSP), now allow quantitative spatially resolved measurement of the transcriptome in tissues. However, the bioinformatics pipelines currently used to analyse GeoMx data often fail to successfully account for the technical variability within the data and the complexity of experimental designs, thus limiting the accuracy and reliability of the subsequent analysis. Carefully designed quality control workflows, that include in-depth experiment-specific investigations into technical variation and appropriate adjustment for such variation can address this issue. Here, we present standR, an R/Bioconductor package that enables an end-to-end analysis of GeoMx DSP data. With four case studies from previously published experiments, we demonstrate how the standR workflow can enhance the statistical power of GeoMx DSP data analysis and how the application of standR enables scientists to develop in-depth insights into the biology of interest.

StellarPath: Hierarchical-vertical multi-omics classifier synergizes stable markers and interpretable similarity networks for patient profiling.

The Patient Similarity Network paradigm implies modeling the similarity between patients based on specific data. The similarity can summarize patients' relationships from high-dimensional data, such as biological omics. The end PSN can undergo un/supervised learning tasks while being strongly interpretable, tailored for precision medicine, and ready to be analyzed with graph-theory methods. However, these benefits are not guaranteed and depend on the granularity of the summarized data, the clarity of the similarity measure, the complexity of the network's topology, and the implemented methods for analysis. To date, no patient classifier fully leverages the paradigm's inherent benefits. PSNs remain complex, unexploited, and meaningless. We present StellarPath, a hierarchical-vertical patient classifier that leverages pathway analysis and patient similarity concepts to find meaningful features for both classes and individuals. StellarPath processes omics data, hierarchically integrates them into pathways, and uses a novel similarity to measure how patients' pathway activity is alike. It selects biologically relevant molecules, pathways, and networks, considering molecule stability and topology. A graph convolutional neural network then predicts unknown patients based on known cases. StellarPath excels in classification performances and computational resources across sixteen datasets. It demonstrates proficiency in inferring the class of new patients described in external independent studies, following its initial training and testing phases on a local dataset. It advances the PSN paradigm and provides new markers, insights, and tools for in-depth patient profiling.

vissE.cloud: a webserver to visualise higher order molecular phenotypes from enrichment analysis.

Gene-set analysis (GSA) dominates the functional interpretation of omics data and downstream hypothesis generation. Despite its ability to summarise thousands of measurements into semantically interpretable components, GSA often results in hundreds of significantly enriched gene-sets. However, summarisation and effective visualisation of GSA results to facilitate hypothesis generation is still lacking. While some webservers provide gene-set visualization tools, there is still a need for tools that can effectively summarize and guide exploration of GSA results. To enable versatility, webservers accept gene lists as input, however, none provide end-to-end solutions for emerging data types such as single-cell and spatial omics. Here, we present vissE.Cloud, a webserver for end-to-end gene-set analysis, offering gene-set summarisation and highly interactive visualisation. vissE.Cloud uses algorithms from our earlier R package vissE to summarise GSA results by identifying biological themes. We maintain versatility by allowing analysis of gene lists, as well as, analysis of raw single-cell and spatial omics data, including CosMx and Xenium data, making vissE.Cloud the first webserver to provide end-to-end gene-set analysis of sub-cellular localised spatial data. Structuring the results hierarchically allows swift interactive investigations of results at the gene, gene-set, and clusters level. vissE.Cloud is freely available at https://www.vissE.Cloud.

Inhibition of the angiotensin II type 2 receptor AT2R is a novel therapeutic strategy for glioblastoma.

Glioblastoma (GBM) is an aggressive malignant primary brain tumor with limited therapeutic options. We show that the angiotensin II (AngII) type 2 receptor (AT2R) is a therapeutic target for GBM and that AngII, endogenously produced in GBM cells, promotes proliferation through AT2R. We repurposed EMA401, an AT2R antagonist originally developed as a peripherally restricted analgesic, for GBM and showed that it inhibits the proliferation of AT2R-expressing GBM spheroids and blocks their invasiveness and angiogenic capacity. The crystal structure of AT2R bound to EMA401 was determined and revealed the receptor to be in an active-like conformation with helix-VIII blocking G-protein or ß-arrestin recruitment. The architecture and interactions of EMA401 in AT2R differ drastically from complexes of AT2R with other relevant compounds. To enhance central nervous system (CNS) penetration of EMA401, we exploited the crystal structure to design an angiopep-2-tethered EMA401 derivative, A3E. A3E exhibited enhanced CNS penetration, leading to reduced tumor volume, inhibition of proliferation, and increased levels of apoptosis in an orthotopic xenograft model of GBM.

Dimensionality Engineering of Magnetic Anisotropy from the Anomalous Hall Effect in Synthetic SrRuO3 Crystals.

Magnetic anisotropy in atomically thin correlated heterostructures is essential for exploring quantum magnetic phases for next-generation spintronics. Whereas previous studies have mostly focused on van der Waals systems, here we investigate the impact of dimensionality of epitaxially grown correlated oxides down to the monolayer limit on structural, magnetic, and orbital anisotropies. By designing oxide superlattices with a correlated ferromagnetic SrRuO3 and nonmagnetic SrTiO3 layers, we observed modulated ferromagnetic behavior with the change of the SrRuO3 thickness. Especially, for three-unit-cell-thick layers, we observe a significant 1500% improvement of the coercive field in the anomalous Hall effect, which cannot be solely attributed to the dimensional crossover in ferromagnetism. The atomic-scale heterostructures further reveal the systematic modulation of anisotropy for the lattice structure and orbital hybridization, explaining the enhanced magnetic anisotropy. Our findings provide valuable insights into engineering the anisotropic hybridization of synthetic magnetic crystals, offering a tunable spin order for various applications.

Defining the relationship between cellular and extracellular vesicle (EV) content in breast cancer via an integrative multi-omic analysis.

Much recent research has been dedicated to exploring the utility of extracellular vesicles (EVs) as circulating disease biomarkers. Underpinning this work is the assumption that the molecular cargo of EVs directly reflects the originating cell. Few attempts have been made, however, to empirically validate this on the -omic level. To this end, we have performed an integrative multi-omic analysis of a panel of breast cancer cell lines and corresponding EVs. Whole transcriptome analysis validated that the cellular transcriptome remained stable when cultured cells are transitioned to low serum or serum-free medium for EV collection. Transcriptomic profiling of the isolated EVs indicated a positive correlation between transcript levels in cells and EVs, including disease-associated transcripts. Analysis of the EV proteome verified that HER2 protein is present in EVs, however neither the estrogen (ER) nor progesterone (PR) receptor proteins are detected regardless of cellular expression. Using multivariate analysis, we derived an EV protein signature to infer cellular patterns of ER and HER2 expression, though the ER protein could not be directly detected. Integrative analyses affirmed that the EV proteome and transcriptome captured key phenotypic hallmarks of the originating cells, supporting the potential of EVs for non-invasive monitoring of breast cancers.

vissE: a versatile tool to identify and visualise higher-order molecular phenotypes from functional enrichment analysis.

Functional analysis of high throughput experiments using pathway analysis is now ubiquitous. Though powerful, these methods often produce thousands of redundant results owing to knowledgebase redundancies upstream. This scale of results hinders extensive exploration by biologists and can lead to investigator biases due to previous knowledge and expectations. To address this issue, we present vissE, a flexible network-based analysis and visualisation tool that organises information into semantic categories and provides various visualisation modules to characterise them with respect to the underlying data, thus providing a comprehensive view of the biological system. We demonstrate vissE's versatility by applying it to three different technologies: bulk, single-cell and spatial transcriptomics. Applying vissE to a factor analysis of a breast cancer spatial transcriptomic data, we identified stromal phenotypes that support tumour dissemination. Its adaptability allows vissE to enhance all existing gene-set enrichment and pathway analysis workflows, empowering biologists during molecular discovery.

Biallelic TYR and TKFC variants in Egyptian patients with OCA1 and new expanded TKFC features.

BACKGROUND: Oculocutaneous albinism type1 (OCA1) is caused by the TYR gene's homozygous and compound heterozygous variants. TKFC gene variants cause triokinase & FMN cyclase deficiency syndrome with variable multisystemic disorders. OBJECTIVES: To determine the potential disease-causing variants in two deceased patients presenting atypical OCA1 features by demonstrating three generations for a single family. The two deceased neonates had severe skeletal abnormalities and fatal hypertrophic cardiomyopathy. We also explored the potential mechanisms for the causative relationship between TKFC and multisystem disorders. PATIENTS AND METHODS: Due to the new emerging symptoms that weren't reported before with the TYR gene, the following methods were performed: Sanger sequencing for the TYR gene, followed by whole exome sequencing, co-segregation, and computational analyses. RESULTS: Extensive parental consanguinity was found, and consequently an autosomal recessive mode of inheritance was prioritized. Upon performing sequencing and segregation data, the following has been confirmed: positive co-segregation of nonsense homozygous NM_000372.5:c.346C > T p.(Arg116*) variant in TYR gene and multisystem disease-missense homozygous NM_015533.4:c.598G > A p.(Val200Ile) variant in TKFC gene in the two affected index patients who deceased due to hypertrophic cardiomyopathy. Using computational analysis, we found that c.598G > A p.(Val200Ile) pathogenicity has led to the failure of L2-K1 active site closure due to the potential differential fluctuation between valine and isoleucine residues. Subsequently, disruption of endogenous DHA phosphorylation was found. Two potential mechanisms exploring the causative relationship between TKFC gene and multisystem disorders have been suggested. CONCLUSIONS: This study presented a first family with the co-existence of biallelic variants in TYR and TKFC genes associating severe skeletal abnormalities and lethal hypertrophic cardiomyopathy. Neither of these genes would have been pursued in the standard genetic counseling. Such discovery is paving the way for more efficient genetic counseling. Comparing TKFC results with literature data showed that our relevant expanded TKFC variant is the 3rd worldwide.

Global and regional governance of One Health and implications for global health security.

The apparent failure of global health security to prevent or prepare for the COVID-19 pandemic has highlighted the need for closer cooperation between human, animal (domestic and wildlife), and environmental health sectors. However, the many institutions, processes, regulatory frameworks, and legal instruments with direct and indirect roles in the global governance of One Health have led to a fragmented, global, multilateral health security architecture. We explore four challenges: first, the sectoral, professional, and institutional silos and tensions existing between human, animal, and environmental health; second, the challenge that the international legal system, state sovereignty, and existing legal instruments pose for the governance of One Health; third, the power dynamics and asymmetry in power between countries represented in multilateral institutions and their impact on priority setting; and finally, the current financing mechanisms that predominantly focus on response to crises, and the chronic underinvestment for epidemic and emergency prevention, mitigation, and preparedness activities. We illustrate the global and regional dimensions to these four challenges and how they relate to national needs and priorities through three case studies on compulsory licensing, the governance of water resources in the Lake Chad Basin, and the desert locust infestation in east Africa. Finally, we propose 12 recommendations for the global community to address these challenges. Despite its broad and holistic agenda, One Health continues to be dominated by human and domestic animal health experts. Substantial efforts should be made to address the social-ecological drivers of health emergencies including outbreaks of emerging, re-emerging, and endemic infectious diseases. These drivers include climate change, biodiversity loss, and land-use change, and therefore require effective and enforceable legislation, investment, capacity building, and integration of other sectors and professionals beyond health.

Dosimetric advantages for cardiac substructures in radiotherapy of esophageal cancer in deep-inspiration breath hold.

BACKGROUND: Radiotherapy is one of the main treatment options for patients with esophageal cancer; however, it has been linked with an increased risk of cardiac toxicities. In the current study, we evaluated the effect of planning the radiation in deep-inspiration breath hold (DIBH) on the dose sparing of cardiac substructures and lung. MATERIALS AND METHODS: In this study, we analyzed 30 radiation therapy plans from 15 patients diagnosed with esophageal cancer planned for neoadjuvant radiotherapy. Radiation plans were generated for 41.4 Gy and delivered in 1.8 Gy per fraction for free-breathing (FB) and DIBH techniques. We then conducted a comparative dosimetric analysis, evaluating target volume coverage, the impact on cardiac substructures, and lung doses across the two planning techniques for each patient. RESULTS: There was no significant disparity in target volume dose coverage between DIBH and FB plans. However, the Dmean, D2%, and V30% of the heart experienced substantial reductions in DIBH relative to FB, with values of 6.21 versus 7.02 Gy (p = 0.011), 35.28 versus 35.84 Gy (p = 0.047), and 5% versus 5.8% (p = 0.048), respectively. The Dmean of the left ventricle was notably lower in DIBH compared to FB (4.27 vs. 5.12 Gy, p = 0.0018), accompanied by significant improvements in V10. Additionally, the Dmean and D2% of the left coronary artery, as well as the D2% of the right coronary artery, were significantly lower in DIBH. The dosimetric impact of DIBH on cardiac substructures proved more advantageous for middle esophageal (ME) than distal esophageal (DE) tumors. CONCLUSION: Radiotherapy in DIBH could provide a method to reduce the radiation dose to the left ventricle and coronaries, which could reduce the cardiac toxicity of the modality.

Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy : A retrospective study.

PURPOSE: Hepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors. METHODS: In this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child-Pugh score (CPS) progression was also explored. RESULTS: SBRT demonstrated 93.4% freedom from local progression (FFLP) at 12 months. Notably, a near minimum dose (D98%) below 61 Gy as an equivalent dose in 2­Gy fractions with α/ß 10 Gy (EQD2α/ß10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed a dose-response relationship for FFLP and D98% with 95% and 98% probability of FFLP at a dose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1 year and 34.3% at 3 years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked a mean EQD2α/ß3-8 dose to the liver (12.8-12.6) with a 10% likelihood of ncRILD. CONCLUSION: SBRT offers a compelling option for achieving high local control and promising survival outcomes in HCC. The study supports a radiation dose range of 61-73.1 Gy, coupled with a mean liver dose under 12.6-12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.

Impact of Graphene Oxide on SERS Enhancement of Arylated Gold Nanospheres: Mechanistic Insight.

The performance of gold nanospheres as substrates for surface-enhanced Raman spectroscopy (SERS) investigation has been compromised by their low adsorption efficiency, high colloidal dispersibility, and diminishing hot spots. However, gold nanosphere substrates modified using aryldiazonium gold(III) chemistry via durable gold-carbon bonds are promising for SERS enhancement due to their controlled organic layer density. In this study, arylated gold nanospheres AuNSs-COOH have shown SERS enhancement when incorporated into graphene oxide (GO) to form nanocomposites (NCs) labeled AuNSs-COOH/GO (AuNCs). Our investigation using X-ray photoelectron spectroscopy (XPS) surface analysis showed that the gold-aryl nanospheres reached their maximum SERS enhancement with an optimal coating. The evaluation included the Au 4f chemical environment and compact graphitic layers for the SERS substrate optimization. The fabricated AuNC substrates demonstrated superior efficiency and reproducibility. A broad linear range of 10-3-10-7 M 4-nitrophenol detection was obtained with exceptional repeatability, as evidenced by the relative standard deviation (RSD) of 9.32%. A detailed investigation of the energy profiles, particularly the valence band maximum (VBM) and band gap values of the substrate and analyte, depicted the electromagnetic (EM) and charge-transfer-induced enhancement and the role of GO inclusion in substrate efficiency in SERS enhancement mechanisms. The finite-difference time domain (FDTD) simulation results revealed that AuNCs incorporated with graphitic nanostructures exhibited the most substantial SERS effect through an EM field enhancement mechanism. This study demonstrated significant SERS enhancement using gold-aryl nanospheres when modified with GO, in contrast to the typical reliance on anisotropic nanostructures.

Flexible Copper Films Modification via Spontaneous Reduction of Aryldiazonium Gold Salts: Unraveling Surface Properties and Energy Profile.

In this study, we report the modification of flexible copper films via the spontaneous reduction of aryldiazonium gold salts [X-4-C6H4N≡N]AuCl4 (X═COOH, NO2). The electroless modification involves dipping of flexible copper films in the aryldiazonium gold solutions for a few seconds, under ambient conditions, followed by a washing step with deionized water to obtain a mechanically robust gold-aryl coating. The chemical composition, morphology, electronic structure, and optical properties of the gold-aryl layer and the flexibility of the modified copper films are supported by the results from X-ray photoelectron spectroscopy (XPS), electrochemistry, contact angle, scanning electron microscopy (SEM), and ultraviolet photoelectron spectroscopy (UPS). XPS surface analysis showed metallic gold in addition to C-C, C-O/C-N, and C═O functional groups from the grafted aryls. Cu 2p showed metallic copper as a major component and a small amount of Cu(II) ions. Wettability studies showed that Au-COOH@Cu increased the contact angle of the bare copper films from 68.0 ± 0.7° to 82.0° ± 0.7°, while Au-NO2@Cu increased the contact angle to 134.0° ± 0.3°. UPS energy profile analysis of [HOOC-4-C6H4N≡N]AuCl4 (valence band maximum = 1.91 eV) exhibited greater reducibility than [O2N-4-C6H4N≡N]AuCl4 (valence band maximum = 2.91 eV). The lower ionization potential of [HOOC-4-C6H4N≡N]AuCl4 (IP = 4.33 eV) enhanced the reactivity upon copper film contact, potentially inducing efficient energy level alignment, compared with [O2N-4-C6H4N≡N]AuCl4 (IP = 5.62 eV). UPS results were further supported by electrochemistry investigation which revealed that [HOOC-4-C6H4N≡N]AuCl4 is easily reducible compared with [O2N-4-C6H4N≡N]AuCl4. The findings presented here hold significant implications for developing flexible copper films and pave the way for future advancements in electronic material modification for industrial applications.

Impact of previously failed extracorporeal shock wave lithotripsy on ureterorenoscopy outcomes in upper urinary tract stones: a prospective comparative study.

OBJECTIVE: We sought to prospectively evaluate the impact of previously failed SWL on subsequent URS outcomes in the treatment of upper urinary tract stones. MATERIALS AND METHODS: Between May 2021 and May 2023, one hundred thirty-six patients with proximal ureteral stones < 1.5 cm and renal stones < 2.5 cm who were candidates for URS were prospectively assigned to a non-SWL group, which included patients without a history of failed SWL before URS, and a post-SWL group, which included patients with a history of failed SWL before URS. The success rate was the primary outcome. The perioperative data of the two groups were compared. RESULTS: The stone-free rate was 83.3% in the post-SWL group versus 81.3% in the non-SWL group, and 8.3% in the post-SWL group versus 9.4% in the non-SWL group had clinically insignificant residual fragments. There was no significant difference in the stone-free rate or success rate between the groups. No significant differences in intraoperative fluoroscopy time, operative time, intraoperative stone appearance, perioperative complications, or the presence of embedded fragments in the ureteral mucosa were detected between the two groups. CONCLUSION: Compared with patients who underwent primary URS, patients who underwent salvage URS for upper urinary tract stones had similar stone-free rates, success rates, operative times, fluoroscopy times, and complication rates without any significant differences.

Assessing the effectiveness of greater occipital nerve block in chronic migraine: a systematic review and meta-analysis.

BACKGROUND & AIMS: Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo. METHODS: A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments. RESULTS: Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups. CONCLUSION: The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

Genetic and virological characteristics of a reassortant avian influenza A H6N1 virus isolated from wild birds at a live-bird market in Egypt.

The first detection of a human infection with avian influenza A/H6N1 virus in Taiwan in 2013 has raised concerns about this virus. During our routine surveillance of avian influenza viruses (AIVs) in live-bird markets in Egypt, an H6N1 virus was isolated from a garganey duck and was characterized. Phylogenetic analysis indicated that the Egyptian H6N1 strain A/Garganey/Egypt/20869C/2022(H6N1) has a unique genomic constellation, with gene segments inherited from different subtypes (H5N1, H3N8, H7N3, H6N1, and H10N1) that have been detected previously in AIVs from Egypt and some Eurasian countries. We examined the replication of kinetics of this virus in different mammalian cell lines (A549, MDCK, and Vero cells) and compared its pathogenicity to that of the ancestral H6N1 virus A/Quail/HK/421/2002(H6N1). The Egyptian H6N1 virus replicated efficiently in C57BL/6 mice without prior adaptation and grew faster and reached higher titers than in A549 cells than the ancestral strain. These results show that reassortant H6 AIVs might pose a potential threat to human health and highlight the need to continue surveillance of H6 AIVs circulating in nature.

Incidence and predictors of ventilator-associated pneumonia using a competing risk analysis: a single-center prospective cohort study in Egypt.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a challenging nosocomial problem in low- and middle-income countries (LMICs) that face barriers to healthcare delivery and resource availability. This study aimed to examine the incidence and predictors of VAP in Egypt as an example of an LMIC while considering death as a competing event. METHODS: The study included patients aged ≥ 18 years who underwent mechanical ventilation (MV) in an intensive care unit (ICU) at a tertiary care, university hospital in Egypt between May 2020 and January 2023. We excluded patients who died or were transferred from the ICU within 48 h of admission. We determined the VAP incidence based on clinical suspicion, radiological findings, and positive lower respiratory tract microbiological cultures. The multivariate Fine-Gray subdistribution hazard model was used to examine the predictors of VAP while considering death as a competing event. RESULTS: Overall, 315 patients were included in this analysis. Sixty-two patients (19.7%) developed VAP (17.1 per 1000 ventilator days). The Fine-Gray subdistribution hazard model, after adjustment for potential confounders, revealed that emergency surgery (subdistribution hazard ratio [SHR]: 2.11, 95% confidence interval [CI]: 1.25-3.56), reintubation (SHR: 3.74, 95% CI: 2.23-6.28), blood transfusion (SHR: 2.23, 95% CI: 1.32-3.75), and increased duration of MV (SHR: 1.04, 95% CI: 1.03-1.06) were independent risk factors for VAP development. However, the new use of corticosteroids was not associated with VAP development (SHR: 0.94, 95% CI: 0.56-1.57). Klebsiella pneumoniae was the most common causative microorganism, followed by Pseudomonas aeruginosa. CONCLUSION: The incidence of VAP in Egypt was high, even in the ICU at a university hospital. Emergency surgery, reintubation, blood transfusion, and increased duration of MV were independently associated with VAP. Robust antimicrobial stewardship and infection control strategies are urgently needed in Egypt.

Can we increase the value of data from bladder diaries? International Consultation on Incontinence-Research Society 2023.

BACKGROUND: Bladder diaries represent a fundamental component in the assessment of patients presenting with lower urinary tract symptoms. Nevertheless, their importance often remains underappreciated and undervalued within clinical practice. This paper aims to conduct a comprehensive review of the existing literature concerning the utility of bladder diaries, underscore the criticality of their precision, elucidate the factors contributing to noncompliance with bladder diary completion, and investigate potential strategies for enhancing patient compliance. MATERIALS AND METHODS: A review of the English-language scientific literature available in the domains of Medline, Embase, Emcare, Midirs, and Cinahl was conducted. This was supplemented by discussion at the International Consultation on Incontinence Research Society Proposal session to define knowledge and identify gaps in knowledge surrounding the utility of bladder diaries. The existing evidence and outcome of the relevant discussion held in the meeting are presented. RESULTS: Bladder diaries (BD) serve to characterize the nature and severity of storage lower urinary tract symptoms (LUTS) and provide an objective record of an individual's urination patterns. They aid in the refinement and customization of treatment strategies based on the clinical responses documented in the diary, optimizing treatment outcomes. Notably, both BD and urodynamic studies (UDS) play complementary yet distinct roles in LUTS evaluation. BD offers a more comprehensive and accessible approach to assessing specific storage LUTS, particularly due to their affordability and widespread availability, especially in resource-limited settings. Nevertheless, the absence of a standardized BD format across global healthcare systems presents a significant challenge. Despite being recognized as reliable, noninvasive, validated, and cost-effective tools for evaluating patients with LUTS, the implementation and completion of BD have proven to be complex. The introduction of automated bladder diaries heralds an era of precise, real-time data collection, potentially enhancing the patient-clinician relationship. Completion of bladder diaries depends on an array of individual, social, and healthcare-specific factors. Compliance with bladder diary completion could be enhanced with clear instructions, patient education, regular follow-ups and positive re-enforcement. This study has identified four critical areas for future research: Addressing healthcare disparities between affluent and developing nations, enhancing the current functionality and effectiveness of bladder diaries, exploring the feasibility of incorporating bladder diaries into the treatment and education process and improving the quality and functionality of existing bladder diaries. CONCLUSION: Bladder diaries play a pivotal role in the evaluation and management of patients with LUTS, providing a holistic perspective. When their complete potential is harnessed, they have the capacity to revolutionize the paradigm of LUTS management, ushering in a patient-centered era of care.

Should hormone replacement therapy (any route of administration) be considered in all postmenopausal women with lower urinary tract symptoms? Report from the ICI-RS 2023.

AIMS: This International Consultation on Incontinence-Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted. METHODS: An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS. RESULTS: There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta-analysis to have a negative effect on LUTS and, therefore are not currently recommended. CONCLUSIONS: Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing.