Diagnostic Approach Research Articles

Acetate-producing bacterium Paenibacillus odorifer hampers lung cancer growth in lower respiratory tract: an in vitro study.

Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications in vitro. We found that Paenibacillus odorifer was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that Paenibacillus odorifer proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that Paenibacillus odorifer functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that Paenibacillus odorifer was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells in vitro. These findings indicated that Paenibacillus odorifer in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.

An open comparative randomized prospective study: Direct trocar insertion vs Veress needle technique in laparoscopic surgeries.

Laparoscopy is a minimally invasive technique utilized for both diagnostic and surgical approaches. Minimally invasive procedures compared to laparotomy offer the advantages of reduced hospital stay, lower morbidity, decreased pain, and faster recovery. Common methods for laparoscopic entry include Veress needle insertion (VNI), direct optical trocar entry, direct trocar insertion (DTI), and the Hasson technique. This study aims to compare the efficacy and safety of VNI and DTI in laparoscopic gynecological surgeries. An open comparative randomized prospective study was conducted involving 200 women aged 18 to 70 years, scheduled for laparoscopic surgery at 2 tertiary centers. Participants were randomized into 2 groups: 1 using VNI and other using DTI. The groups were homogeneous regarding age, parity, and body mass index. The mean age of the VNI group is 45.22 ± 11.65 and the DTI group is 44.89 ± 10.5 (P = .833). There were no statistical significance in terms of the presence of chronic diseases and history of previous abdominal surgery between the groups (P = .802 and P = .510, respectively). Entry time to the abdomen, the decrease in hemoglobin values, and hospitalization length were found to be statistically significant between the entry methods (P < .001, P = .002, and P < .001, respectively). Entry time, the decrease in hemoglobin value, and hospitalization length were higher in the VNI group. In conclusion, although there is no definitive consensus on the optimal laparoscopic entry technique, direct trocar entry is an effective alternative to the Veress needle insertion technique. Direct trocar entry is associated with shorter entry times, fewer perioperative complications, less reduction in hemoglobin levels, and shorter hospitalization duration compared to VNI.

Refractory gastroduodenal ulcers: investigating non-peptic etiologies.

This article presents two clinical cases of gastroduodenal peptic ulcers refractory to medical treatment. In both cases, malignancy was excluded following persistent lesions observed in repeated endoscopies, leading to the use of surgery as both a diagnostic and therapeutic approach. These refractory cases require a multidisciplinary approach with a broad differential diagnosis, including etiologies such as toxic substance exposure, persistent Helicobacter pylori infection, or poor adherence to medical treatment, along with less common conditions such as malignancy, acid hypersecretion syndromes, vascular disorders, or immune-mediated diseases.

Case Report: Spontaneous cornual Pregnancy at 7 Weeks: A Gynecological challenge

Introduction and Importance Cornual pregnancy (CP) is a rare and dangerous type of ectopic pregnancy, occurring in 2% to 4% of cases. Due to its atypical location in the uterine horn, it poses a high risk for severe complications, such as rupture of the uterus, and life-threatening bleeding, particularly when diagnosis is delayed. Case Presentation We report the case of a 35-year-old female patient presenting with severe pelvic pain and vaginal bleeding, with 12 weeks of amenorrhea. Clinical evaluation revealed elevated β-HCG levels and transvaginal ultrasound showed a 7-week unruptured right cornual pregnancy. Surgical management involved a mini-laparotomy, which confirmed the diagnosis and a cornuostomy along with a right salpingectomy was performed. The patient’s postoperative course was uneventful, and follow-up confirmed complete recovery. Clinical Discussion Cornual pregnancies, though rare, carry a significant risk of serious complications and maternal death due to delayed diagnosis. Risk factors encompass a history of miscarriage, elective abortion, sexually transmitted infections, and smoking, all contributing to abnormal implantation. Early diagnosis is challenging but crucial, with ultrasound being key for detection. Management depends on gestational age, patient stability, and future reproductive plans, with methotrexate or surgical intervention being standard options. Conclusion Cornual pregnancy, despite its rarity, demands prompt and accurate diagnosis to prevent catastrophic outcomes. This case underscores the need for individualized treatment strategies and highlights the importance of early intervention. Ongoing research is vital to improving diagnostic approaches and therapeutic outcomes.

Assessment of the circulating levels of immune system checkpoint selected biomarkers in patients with lung cancer.

Lung cancer is recognized as one of the leading causes of cancer-related deaths globally, with a significant increase in incidence and intricate pathogenic mechanisms. This study examines the expression profiles of Programmed Cell Death Protein 1 (PD-1), PD-1 ligand (PDL-1), β-catenin, CD44, interleukin 6 (IL-6), and interleukin 10 (IL-10), as well as their correlations with the clinic-pathological features and diagnostic significance in lung cancer patients. The research involved lung cancer patients exhibiting various pathological characteristics, alongside demographically matched healthy controls. The expression levels of PD-1, PDL-1, β-catenin, and CD44 were analyzed using Real-Time PCR, while circulating levels of IL-6 and IL-10 were assessed through ELISA assays. This investigation focused on peripheral blood mononuclear cells (PBMC) to evaluate these factors non-invasively. Findings indicated that levels of PD-1, PDL-1, and CD44 were significantly elevated in patients compared to controls, which coincided with a decrease in β-catenin levels. Additionally, a concurrent rise in IL-6 and IL-10, both pro-inflammatory cytokines, was observed in patients, suggesting a potential regulatory role for these cytokines on the PD-1/PDL-1 axis, which may help tumors evade immune system checkpoints. The predictive value of these factors concerning lung tumors and metastasis was significant (Regression analysis). Furthermore, these markers demonstrated diagnostic potential in differentiating between patients and healthy controls, as well as between individuals with metastatic and non-metastatic tumors (ROC curve analysis). This study provides insights into the expression profiles of PD-1/PDL-1 immune system checkpoints and their regulatory factors in lung cancer, potentially paving the way for new therapeutic and diagnostic approaches.

A gold nanoparticle conjugated single-legged DNA walker driven by catalytic hairpin assembly biosensor to detect a prokaryotic pathogen

Catalytic hairpin assembly (CHA)-DNA walker allows nanostructures to spontaneously hybridize to the nucleic acids. The localized surface plasmon resonance provides the ability of color-shift for Au nanoparticles (AuNPs) to design a colorimetric biosensor by implementing CHA-DNA walker reaction on AuNPs. A target gene in Klebsiella pneumoniae as the reaction cascade trigger, was selected. H1 and H2 oligonucleotides as the components of the system were designed and verified by NUPACK. The AuNPs were conjugated to H1. The conjugation of the probes to the AuNPs was evaluated using FT-IR. The signal amplification process was conducted at 25℃. TEM imaging, zeta potential, spectroscopy, and gel-electrophoresis were used to examine the conduction of the reaction cascade and specificity. The sensitivity of the method was analyzed using serial dilution of the target. The formation of over-52 bp intermediate secondary structures (which only exist when the reaction happens) was confirmed by gel-electrophoresis. The color distinction between positive (0.08 to 0.058) and negative samples (0.098 to 0.05) was evidenced instantly and in a period of 90 min of the reaction as a drop change of 520 nm intensity absorbance. TEM imaging confirmed the further distance of AuNPs in the positive sample in comparison to that of the negative sample which reveals effective detection of the pathogen. The LOD of the technique was measured as 2.5 nM of the target sequence. The diagnostic approach is a label-free, enzyme-independent approach and can be executed in a single step. It has been designed by employing the CHA-DNA walker system along with the colorimetric properties of AuNPs for the first time, thereby paving the way for more rapid and accurate diagnostic kits.

Aberrant individual large-scale functional network connectivity and topology in chronic insomnia disorder with and without depression

Insomnia is increasingly prevalent with significant associations with depression. Delineating specific neural circuits for chronic insomnia disorder (CID) with and without depressive symptoms is fundamental to develop precision diagnosis and treatment. In this study, we examine static, dynamic and network topology changes of individual large-scale functional network for CID with (CID-D) and without depression to reveal their specific neural underpinnings. Seventeen individual-specific functional brain networks are obtained using a regularized nonnegative matrix factorization technique. Disorders-shared and -specific differences in static and dynamic large-scale functional network connectivities within or between the cognitive control network, dorsal attention network, visual network, limbic network, and default mode network are found for CID and CID-D. Additionally, CID and CID-D groups showed compromised network topological architecture including reduced small-world properties, clustering coefficients and modularity indicating decreased network efficiency and impaired functional segregation. Moreover, the altered neuroimaging indices show significant associations with clinical manifestations and could serve as effective neuromarkers to distinguish among healthy controls, CID and CID-D. Taken together, these findings provide novel insights into the neural basis of CID and CID-D, which may facilitate developing new diagnostic and therapeutic approaches.

Discogenic Low Back Pain: Anatomic and Pathophysiologic Characterization, Clinical Evaluation, Biomarkers, AI, and Treatment Options.

Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, a common yet complex cause of chronic pain, defined by fissuring in the annulus fibrosus resulting in vascularization of growing granulation tissue and growth of nociceptive nerve fibers along the laceration area. This paper delves into the anatomical and pathophysiological underpinnings of discogenic LBP, emphasizing the role of intervertebral disc degeneration in the onset of pain. The pathogenesis is multifactorial, involving processes like mitochondrial dysfunction, accumulation of advanced glycation end products, and pyroptosis, all contributing to disc degeneration and subsequent pain. Despite its prevalence, diagnosing discogenic LBP is challenging due to the overlapping symptoms with other forms of LBP and the absence of definitive diagnostic criteria. Current diagnostic approaches include clinical evaluations, imaging techniques, and the exploration of potential biomarkers. Treatment strategies range from conservative management, such as physical therapy and pharmacological interventions, to more invasive procedures such as spinal injections and surgery. Emerging therapies targeting molecular pathways involved in disc degeneration are under investigation and hold potential for future clinical application. This paper highlights the necessity of a multidisciplinary approach combining clinical, imaging, and molecular data to enhance the accuracy of diagnosis and the effectiveness of treatment for discogenic LBP, ultimately aiming to improve patient outcomes.

Multi-omics analysis reveals the key factors involved in the severity of the Alzheimer’s disease

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder with a global impact, yet its pathogenesis remains poorly understood. While age, metabolic abnormalities, and accumulation of neurotoxic substances are potential risk factors for AD, their effects are confounded by other factors. To address this challenge, we first utilized multi-omics data from 87 well phenotyped AD patients and generated plasma proteomics and metabolomics data, as well as gut and saliva metagenomics data to investigate the molecular-level alterations accounting the host-microbiome interactions. Second, we analyzed individual omics data and identified the key parameters involved in the severity of the dementia in AD patients. Next, we employed Artificial Intelligence (AI) based models to predict AD severity based on the significantly altered features identified in each omics analysis. Based on our integrative analysis, we found the clinical relevance of plasma proteins, including SKAP1 and NEFL, plasma metabolites including homovanillate and glutamate, and Paraprevotella clara in gut microbiome in predicting the AD severity. Finally, we validated the predictive power of our AI based models by generating additional multi-omics data from the same group of AD patients by following up for 3 months. Hence, we observed that these results may have important implications for the development of potential diagnostic and therapeutic approaches for AD patients.

The branched N-glycan of PD-L1 predicts immunotherapy responses in patients with recurrent/metastatic HNSCC

Immunotherapy has revolutionized cancer treatment, but the lack of a reliable predictive biomarker for treatment response remains a challenge. Alpha-1,6-Mannosylglycoprotein 6-β-N-Acetylglucosaminyltransferase 5 (MGAT5) is a key regulator of complex N-glycan synthesis, and its dysregulation is associated with cancer progression. The lectin Phaseolus vulgaris leukoagglutinin (PHA-L) specifically binds to mature MGAT5 products. Previous studies have indicated elevated PHA-L staining in head and neck squamous cell carcinoma (HNSCC), which implies increased activity of MGAT5. However, the specific role of MGAT5 in HNSCC remains unclear. In this study, we found significantly higher PHA-L staining and MGAT5 expression in HNSCC tumors compared to adjacent non-tumor tissues. Using a mass spectrometry (MS)-based glycoproteomic approach, we identified 163 potential protein substrates of MGAT5. Functional analysis revealed that protein substrates of MGAT5 regulated pathways related to T cell proliferation and activation. We further discovered that PD-L1 was among the protein substrates of MGAT5, and the expression of MGAT5 protected tumor cells from cytotoxic T lymphocyte (CTL) killing. Treatment of nivolumab alleviated the protective effects of MGAT5 on CTL activity. Consistently, patients with MGAT5-positive tumors showed improved responses to immunotherapy compared to those with MGAT5-negative tumors. Using purified PD-L1 from HNSCC cells and a glycoproteomic approach, we further deciphered that the N35 and N200 sites carry the majority of complex N-glycans on PD-L1. Our findings highlight the critical role of MGAT5-mediated branched N-glycans on PD-L1 in modulating the interaction with the immune checkpoint receptor PD-1. Consequently, we propose that MGAT5 could serve as a biomarker to predict patients’ responses to anti-PD-1 therapy. Furthermore, targeting the branched N-glycans at N35 and N200 of PD-L1 may lead to the development of novel diagnostic and therapeutic approaches.

A Systematic Review of Metabolic Syndrome: Key Correlated Pathologies and Non-Invasive Diagnostic Approaches.

Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.

Peripheral Neuropathic Pain.

This article synthesizes current knowledge on neuropathic pain, with a brief review of mechanisms, diagnostic approaches, and treatment strategies to help neurologists provide effective and individualized care for patients with this complex condition. The most promising developments in peripheral neuropathic pain are related to the molecular biology of the peripheral nervous system. Systematic molecular and genetic analyses of peripheral nerve terminals and dorsal root ganglia have advanced our understanding of the genetics of function and disease of peripheral nerves, as well as their physiology and clinical manifestations. Peripheral neuropathic pain, similar to central neuropathic pain, is primarily influenced by the biology and pathophysiology of the underlying structures, peripheral sensory nerves, and their central pathways. The clinical course is widely variable in sensory symptoms and intensities, natural history, and response to treatments.

Diagnosis and Management of Immune Checkpoint Inhibitor-Associated Nephrotoxicity: A Position Statement from the American Society of Onco-nephrology

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of renal immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), though glomerular disease and electrolyte disturbances have also been reported. In this position statement by the American Society of Onco-nephrology (ASON), we summarize the incidence and risk factors for ICI-AKI, pathophysiological mechanisms and clinicopathological features of ICI-AKI. We also discuss novel diagnostic approaches and promising biomarkers for ICI-AKI. From expert panel consensus, we provide clinical practice points for the initial assessment and diagnosis of ICI-AKI, management and immunosuppressive therapy, and consideration for re-challenge with ICI following AKI episodes. In addition, we explore ICI use in special populations such as kidney transplant recipients and propose key areas of focus for future research and clinical investigation.

Unsupervised identification of zone-level anomalies in VAV terminal units utilizing autoencoders and PCA

The effective operation of HVAC systems is crucial to minimize energy inefficiencies and occupant discomfort. However, these systems can experience various problems, including hardware and software-related anomalies. In contrast to most existing fault detection and diagnostic approaches, which rely on simple rules and alarms, this study introduces novel unsupervised approaches for detecting zone anomalies in variable air volume (VAV) air handling units (AHUs). The methods utilize autoencoders (AE) and principal component analysis (PCA). To evaluate the effectiveness of the proposed methods, both a synthetic dataset and measured data from a 28-zone VAV AHU system were investigated. The proposed method successfully detected several zone temperature and airflow anomalies using the AE-based method, and several zone anomalies were also identified using the PCA-AE approach by considering four commonly available zone-level trend logs in VAV AHUs namely temperature, airflow, airflow set-point, and VAV terminal damper position. The findings demonstrated the great adaptability of the proposed methods in detecting a wide range of zone anomalies in any modern building equipped with VAV AHUs, giving operators valuable insights about the system and notifying them of potential faults at an early stage.

Diagnosis and Treatment of Hematuria

Hematuria is a common manifestation caused by various factors such as infection, inflammation, trauma, urinary stone and malignancy. Hematuria reflects pathological state of urinary system. Isolated microscopic hematuria without any abnormalities besides of hematuria on urine microscopic examination usually presents a good clinical course or outcome. However, significant proteinuria or hypertension, which accelerates renal dysfunction, can often develop during follow-up period in patients with isolated microscopic hematuria. Compared with non-glomerular hematuria, glomerular hematuria shows several characteristic findings such as dysmorphic red blood cell (RBC) or RBC casts or significant proteinuria on urinalysis. If glomerular hematuria is strongly suspected, a kidney biopsy may be required to differentiate the cause of glomerulonephritis. In this review, we tried to review the differential diagnosis and diagnostic approach and treatment of hematuria.

Quantification of cancer biomarkers in urine using volatilomic approach

Urine analysis is an attractive approach for non-invasive cancer diagnostics. In this study, a procedure for the determination of volatile organic compounds (VOCs) in human urine (acetone, acetonitrile, dimethylsulfide, dimethyl disulfide, dimethyl trisulfide, hexane, benzene, toluene, 2-butanone, 2-pentanone, pentanal) has been described including sample preparation using preconcentration of analytes in sorbent tubes followed by gas chromatography with mass spectrometry (GC-MS). Fractional factorial design and constrained surfaces design were used to optimize preconcentration of VOCs in sorbent tubes. The procedure was validated by analysis of synthetic urine containing VOC standards in the concentration range of 1–5000 ng/mL. Optimized procedure was applied to analyze urine samples of 89 healthy volunteers and 85 patients with cancer of various localizations: 42 patients with lung cancer, 25 – colon, 3 – stomach, 2 – prostate, 2 – esophageal, 2 – pancreas, 2 – kidney, 1 – ovarian, 1 – cervical, 1 – skin, 1 – liver. Concentrations of 2-butanone, 2-pentanone, acetonitrile, and benzene were found different in urine of patients with cancer and healthy individuals. Influence of cancer localization and tumor, nodule, metastasis stage on urine VOC profile was considered. The approach of using ratios of VOCs to the main ones instead of concentrations was considered. A diagnostic model based on significantly different VOC ratios was created to classify healthy individuals and patients with cancer using artificial neural network (ANN). The model was validated during construction by means of 3-fold cross-validation. Average area under receiver operating characteristic (ROC) curve on test dataset was 0.886. Average sensitivity and specificity of the created model were 91 % and 82 %.

Self-Reported Management of Inflammatory Breast Cancer Among the American Society of Breast Surgeons Membership: Consensus and Opportunities.

Inflammatory breast cancer (IBC) is rare and biologically aggressive. We sought to assess diagnostic and management strategies among the American Society of Breast Surgeons (ASBrS) membership. An anonymous survey was distributed to ASBrS members from March to May 2023. The survey included questions about respondents' demographics and information related to stage III and IV IBC management. Agreement was defined as a shared response by >80% of respondents. In areas of disagreement, responses were stratified by years in practice, fellowship training, and annual IBC patient volume. The survey was administered to 2337 members with 399 (17.1%) completing all questions and defining the study cohort. Distribution of years in practice was 26.0% 0-10 years, 26.6% 11-20 years and 47.4% > 20 years. Overall, 51.2% reported surgical oncology or breast fellowship training, 69.2% maintain a breast-only practice, and 73.5% treat < 5 IBC cases/year. Agreement was identified in diagnostic imaging, trimodal therapy, and mastectomy with wide skin excision for stage III IBC. Lack of agreement was identified in surgical management of the axilla; respondents with < 10 years in practice or fellowship training were more likely to perform axillary dissection for cN0-N2 stage III IBC. Locoregional management of stage IV IBC was variable. Among ASBrS members, there is consensus in diagnostic evaluation, treatment sequencing and surgical approach to the breast in stage III IBC. Differences exist in surgical management of the cN0-2 axilla with uptake of de-escalation strategies. Clinical trials are needed to evaluate oncologic safety of de-escalation in this high-risk population.

Controversies in the Management of Acute Pulmonary Embolism in the Emergency Department

Backgroundacute pulmonary embolism is frequently diagnosed in the Emergency Department, and the management approach can be nuanced. Objective: in this narrative review, we synthesize the literature in selected areas of ongoing controversy regarding the diagnostic and management approaches for acute pulmonary embolism (PE) in the Emergency Department, and provide evidence-based recommendations to empower emergency physicians to provide optimal care in these situations. DiscussionD-dimer is used to clinically exclude the diagnosis of PE patients who are stratified as low risk. However by utilizing likelihood ratio and with certain scoring tools, patient historically considered moderate or high risk for PE may safely be able to have the diagnosis excluded with a negative D-dimer. Traditional risk stratification and management strategies can be cautiously applied to patients with concomitant Coronavirus-19 infection while awaiting more definitive studies. There is an increasing trend in the diagnosis of isolated subsegmental PE, and many patients receiving this diagnosis may be treated without anticoagulation provided that they have no evidence of associated DVT and can be closely followed as an outpatient. There is a persistent hesitancy to discharge patients with newly-diagnosed acute PE, and existing well-supported risk stratification tools and clinical decision frameworks can support the emergency physician's decision to safely discharge low-risk patients. Conclusion: this review of the literature empowers emergency clinicians to manage challenging PE cases in the ED.

The Integration of Radiomics and Artificial Intelligence in Modern Medicine.

With profound effects on patient care, the role of artificial intelligence (AI) in radiomics has become a disruptive force in contemporary medicine. Radiomics, the quantitative feature extraction and analysis from medical images, offers useful imaging biomarkers that can reveal important information about the nature of diseases, how well patients respond to treatment and patient outcomes. The use of AI techniques in radiomics, such as machine learning and deep learning, has made it possible to create sophisticated computer-aided diagnostic systems, predictive models, and decision support tools. The many uses of AI in radiomics are examined in this review, encompassing its involvement of quantitative feature extraction from medical images, the machine learning, deep learning and computer-aided diagnostic (CAD) systems approaches in radiomics, and the effect of radiomics and AI on improving workflow automation and efficiency, optimize clinical trials and patient stratification. This review also covers the predictive modeling improvement by machine learning in radiomics, the multimodal integration and enhanced deep learning architectures, and the regulatory and clinical adoption considerations for radiomics-based CAD. Particular emphasis is given to the enormous potential for enhancing diagnosis precision, treatment personalization, and overall patient outcomes.

The emerging role of bacterial extracellular vesicles in human cancers.

Bacterial extracellular vesicles (BEVs) have emerged as pivotal mediators between bacteria and host. In addition to being crucial players in host homeostasis, they have recently been implicated in disease pathologies such as cancer. Hence, the study of BEVs represents an intriguing and rapidly evolving field with substantial translational potential. In this review, we briefly introduce the fundamentals of BEV characteristics, cargo and biogenesis. We emphatically summarize the current relationship between BEVs across various cancer types, illustrating their role in tumorigenesis, treatment responses and patient survival. We further discuss the inherent advantages of BEVs, such as stability, abundance and specific cargo profiles, that make them attractive candidates for non-invasive diagnostic and prognostic approaches. The review also explores the potential of BEVs as a strategy for cancer therapy, considering their ability to deliver therapeutic agents, modulate the tumour microenvironment (TME) and elicit immunomodulatory responses. Understanding the clinical significance of BEVs may lead to the development of better-targeted and personalized treatment strategies. This comprehensive review evaluates the current progress surrounding BEVs and poses questions to encourage further research in this emerging field to harness the benefits of BEVs for their full potential in clinical applications against cancer.