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Molecules (Basel, Switzerland) Jun 2024An untargeted metabolomic study identified four potential lung cancer diagnostic biomarkers in human urine. One of the potential biomarkers was an unidentified feature...
An untargeted metabolomic study identified four potential lung cancer diagnostic biomarkers in human urine. One of the potential biomarkers was an unidentified feature possessing a / value of 561+. "561+" was isolated from human urine and tentatively identified as 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol glucuronide with unknown C24,25 stereochemistry using H NMR and mass spectrometry. In a prior report, the C24,25 stereochemistry of the aglycone, 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol, was found to be 24,25 through GC analysis of the acetonide-TMS derivative. An authentic sample was prepared and found not to have the same stereochemistry as "561+". To identify the C24,25 stereochemistry, four C24,C25 diastereoisomeric alcohols of 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol were prepared from chiral amino acids. Using an LCMS method, the C24,C25 stereochemistry of the "561+" aglycone was determined to be 24,25. With the correct aglycone in hand, it was coupled with glucuronic acid to complete the first reported synthesis of 27-nor-5β-cholestane-3α,7α,12α,24,25S pentol glucuronide. Deuterium labeled 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol was also synthesized for use as an internal standard for MS quantitation.
Topics: Humans; Lung Neoplasms; Biomarkers, Tumor; Glucuronides; Deuterium; Male; Female
PubMed: 38930845
DOI: 10.3390/molecules29122781 -
Microorganisms May 2024Respiratory diseases arising from co-infections involving () and (Mo) pose a substantial threat to the sheep industry. This study focuses on the isolation and...
Respiratory diseases arising from co-infections involving () and (Mo) pose a substantial threat to the sheep industry. This study focuses on the isolation and identification of the strain extracted from the lung tissue of an argali hybrid sheep infected with Mo. Kunming mice were used as a model to assess the pathogenicity of . Subsequently, whole genome sequencing (WGS) of was conducted using the Illumina NovaSeq PE150 platform. The whole genome sequencing analysis involved the construction of an evolutionary tree to depict conserved genes and the generation of a genome circle diagram. identified as serotype A, was named SHZ01. Our findings reveal that SHZ01 infection induces pathological manifestations, including hemorrhage and edema, in mice. The phylogenetic tree of conserved genes analyzing from different countries and different host sources indicates close relatedness between the SHZ01 strain and the 40540 strain (A:12), originating from turkeys in Denmark. The genome of SHZ01 comprises 2,378,508 base pairs (bp) with a GC content of 40.89%. Notably, this strain, designated , exhibits two distinct gene islands and harbors a total of 80 effector proteins associated with the Type III Secretion System (T3SS). The SHZ01 strain harbors 82 virulence genes and 54 resistance genes. In the SHZ01 strain, the proteins, genes, and related GO and KEGG pathways have been annotated. Exploring the relationship between these annotations and the pathogenicity of the SHZ01 strain would be valuable. This study holds great significance in further understanding the pathogenesis and genetic characteristics of the sheep-derived SHZ01 strain. Additionally, it contributes to our understanding of respiratory diseases in the context of co-infection.
PubMed: 38930454
DOI: 10.3390/microorganisms12061072 -
Microorganisms May 2024Leptospirosis is an infectious disease that affects domestic animals, wild animals, and humans. It represents a public health problem and has an important economic...
Leptospirosis is an infectious disease that affects domestic animals, wild animals, and humans. It represents a public health problem and has an important economic impact on livestock. This study aims to investigate the importance of genital and transplacental infection in the epidemiology of leptospirosis in cows maintained in Caatinga biome conditions, Northeastern Brazil, as well as reporting organs colonized by spp. in embryos and fetuses. Blood, urinary tract (urine, bladder, and kidney), and reproductive tract (vaginal fluid, uterus, uterine tube, ovary, and placenta) samples were collected from 15 slaughtered pregnant cows. Two embryos and 13 fetuses were sampled. Central nervous system and choroid ovoid samples were collected from embryos. Blood, central nervous system, lung, peritoneal liquid, abomasal content, liver, spleen, urine, bladder, kidney, and reproductive system samples were collected from fetuses. Diagnostic methods included the microscopic agglutination test (MAT) using a collection of 24 serovars belonging to 17 different pathogenic serogroups of five species as antigens, as well as polymerase chain reaction (PCR). Anti- spp. antibodies were found in 9 cows (60%), while 13 cows (86.67%) had at least one organ or urine with leptospiral DNA. No fetus was seroreactive. Among the embryos and fetuses, 13 (86.67%) presented leptospiral DNA, proving a high frequency of transplacental infection (100%). For cows, the most frequent biological materials regarding spp. DNA detection were placenta (13 out of 15 samples; 86.7%), uterus (10 out of 15 samples; 66.7%), and vaginal fluid (5 out of 15 samples; 33.3%), while, for fetuses/embryos, the most frequent PCR-positive samples were choroid ovoid (1/2; 50%), spleen (6/13; 46.2%), kidney (5/13; 38.5%), and central nervous system (5/15; 33.3%). Sequenced samples based on the LipL32 gene presented 99% similarity with . The results indicate that transplacental infection is an efficient way of spreading spp. in cows maintained in Caatinga biome conditions. Therefore, prevention and control strategies must include actions that interrupt transmission through this alternative route.
PubMed: 38930426
DOI: 10.3390/microorganisms12061044 -
Journal of Clinical Medicine Jun 2024: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic...
: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic options. This manuscript aims to provide a multicenter trial in a real-life setting on Mepolizumab treatment for severe uncontrolled CRSwNP with or without comorbid asthma. : A retrospective data analysis was jointly conducted at the Otolaryngology-Head and Neck Surgery departments of La Sapienza University and San Camillo Forlanini Hospital in Rome. Both institutions participated by sharing clinical information on patients with CRSwNP treated with Mepolizumab. Patients were evaluated before starting Mepolizumab, at six months and at twelve months from the first drug administration. During follow-up visits, patients underwent endoscopic evaluation, quality of life assessment, nasal symptoms assessment, and blood tests to monitor mainly neutrophils, basophils, eosinophils, and IgG, IgA, and IgE assay. : Twenty patients affected by CRSwNP and treated with Mepolizumab were enrolled (12 females and 8 males with a mean age of 63.7 years). Sixteen patients (80%) had concomitant asthma. During follow-up, a gradual improvement in nasal polyp score, quality of life and nasal symptoms, assessed by SNOT-22 and VAS and loss of smell measured by olfactory VAS, was found. Regarding blood tests, eosinophils decreased gradually, while other blood parameters showed no statistically significant changes. : Mepolizumab has been shown to be effective in the therapeutic management of patients with CRSwNP. Further studies are needed to support our findings and better understand the underlying immune pathways to predict patients' response to biological treatment in CRSwNP.
PubMed: 38930104
DOI: 10.3390/jcm13123575 -
Journal of Clinical Medicine Jun 2024The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their...
The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14-0.69) vs. 1.73 (0.5-6.9) ng/mL, < 0.001, 6.3 (2.4-11.8) vs. 19 (10.7-24.8) mg/dl, < 0.001 and 6 (3.7-8.6) vs. 9.8 (5.3-16.3), = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04-0.58, = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, < 0.001, 0.78, < 0.001, and 0.68, = 0.015, respectively). A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia.
PubMed: 38930085
DOI: 10.3390/jcm13123557 -
Journal of Clinical Medicine Jun 2024Severe asthma often remains uncontrolled despite optimized inhaled treatment. The rise of biologic therapy in severe asthma represented a major advance for the disease...
Severe asthma often remains uncontrolled despite optimized inhaled treatment. The rise of biologic therapy in severe asthma represented a major advance for the disease management. However, correct phenotyping and monitoring of severe asthma patients is key to the success of targeted biologic therapy. We present the case of a 63-year-old female, never a smoker, diagnosed with asthma at the age of 45 and associated persistent mild rhinitis, without other notable comorbidities. She was prescribed medium-dose ICS/LABA, administered inconstantly in the first years after the diagnosis, with poor overall control of the disease. After several exacerbation episodes, treatment compliance improved, but the control of the disease remained poor despite adding an antileukotriene. In January 2019, she presented an exacerbation episode requiring treatment with oral corticosteroids (OCS) and she was afterwards put on high-dose ICS/LABA and continued the antileukotriene. She was referred for a skin allergy test, which revealed mild sensitization to Dermatophagoides pteronyssinus and farinae, with a total IgE level of 48.3 IU/mL. The blood eosinophil level was 270 cells/mm. The lung function was variable, going from mild impairment to severe fixed obstruction during exacerbations. Despite optimized inhaled treatment, good adherence and inhaler technique, and allergen avoidance strategies, asthma control was not achieved, and she continued to experience severe episodes of exacerbation requiring OCS. In October 2019, she was initiated on biologic therapy with omalizumab, which allowed asthma control to be achieved and maintained for 18 months, with preserved lung function, good symptom control, no exacerbations and slightly elevated blood eosinophil level (340-360 cells/mm). In April 2021, she started experiencing exacerbation episodes requiring OCS (three episodes within 6 months), with a progressive increase in blood eosinophil level (up to 710 cells/mm), and progressive deterioration of asthma control and lung function, despite continuation of previous therapy. A specific IgE test against Aspergillus was negative, and total IgE level was 122.4 IU/mL. In December 2021, the patient was switched from omalizumab to benralizumab. Asthma control was again achieved, lung function improved significantly and the patient did not experience any other exacerbation episodes up until today, which allowed for a reduction in ICS dose. Intriguingly, a relapsing eosinophilia was also noted under anti-IL5-R treatment prior to the dose administration, but with preserved asthma control. This case underscores the pivotal role of meticulous phenotyping in severe asthma management on one side, and careful monitoring of patient evolution and possible side effects of treatment on the other side. By showcasing how diverse inflammatory pathways can coexist within a single patient and impact treatment outcomes, it highlights the necessity of tailored biologic therapy for sustained control.
PubMed: 38929930
DOI: 10.3390/jcm13123402 -
Journal of Personalized Medicine Jun 2024Despite advancements in artificial intelligence-based decision-making, transitioning patients from intensive care units (ICUs) to low-acuity wards is challenging,...
Development of a Simple Scoring System for Predicting Discharge Safety from the Medical ICU to Low-Acuity Wards: The Role of the Sequential Organ Failure Assessment Score, Albumin, and Red Blood Cell Distribution Width.
Despite advancements in artificial intelligence-based decision-making, transitioning patients from intensive care units (ICUs) to low-acuity wards is challenging, especially in resource-limited settings. This study aimed to develop a simple scoring system to predict ICU discharge safety. We retrospectively analyzed patients admitted to a tertiary hospital's medical ICU (MICU) between July 2016 and December 2021. This period was divided into two phases for model development and validation. We identified risk factors associated with unexpected death within 14 days of MICU discharge and developed a predictive scoring system that incorporated these factors. We verified the system's performance using validation data. In the development cohort, 522 patients were discharged from the MICU, and 42 (8.04%) died unexpectedly. In multivariate analysis, the Sequential Organ Failure Assessment (SOFA) score (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.13-1.41), red blood cell distribution width (RDW) (OR 1.20, 95% CI 1.07-1.36), and albumin (OR 0.37, 95% CI 0.16-0.84) were predictors of unexpected death. Each variable was assigned a weighted point in the scoring system, and the area under the curve (AUC) was 0.788 (95% CI 0.714-0.855). The scoring system was performed using an AUC of 0.738 (95% CI 0.653-0.822) in the validation cohort of 343 patients with 9.62% of unexpected deaths. When a cut-off of 0.032 was applied, a sensitivity and a specificity of 81.8% and 55.2%, respectively, were achieved. This simple bedside predictive score for ICU discharge uses the SOFA score, albumin level, and RDW to aid in timely decision-making and optimize critical care facility allocation in resource-limited settings.
PubMed: 38929864
DOI: 10.3390/jpm14060643 -
Journal of Personalized Medicine Jun 2024Overlap syndrome (OS), the coexistence of chronic obstructive pulmonary disease and obstructive sleep apnea, is frequently characterized by the presence of daytime...
BACKGROUND
Overlap syndrome (OS), the coexistence of chronic obstructive pulmonary disease and obstructive sleep apnea, is frequently characterized by the presence of daytime hypercapnia (pCO ≥ 45 mmHg). The aim of this study was to investigate potential differences in anthropometric, sleep and respiratory characteristics between hypercapnic and normocapnic patients with OS.
METHODS
Consecutive patients who underwent polysomnography, pulmonary function testing and arterial blood gases and had been diagnosed with OS were enrolled in the study.
RESULTS
According to pCO levels in wakefulness, the patients were divided into group A, consisting of OS patients without hypercapnia ( = 108) or group B, consisting of OS patients with hypercapnia ( = 55). The majority of included patients in both groups were males ( = 92 in group A vs. = 50 in group B). Group B had increased BMI ( = 0.001), neck ( = 0.017) and waist circumference ( = 0.013), higher scores in Epworth sleepiness scale (ESS) ( = 0.008), increased sleep efficiency ( = 0.033), oxygen desaturation index ( = 0.004) and time with oxyhemoglobin saturation <90% ( = 0.006) than group A. Also, Group B had decreased average and minimum oxyhemoglobin saturation during sleep ( < 0.001). Hypercapnic patients had lower FEV% ( = 0.003), FVC% ( = 0.004), pO and pCO ( < 0.001 for both) values compared with normocapnic patients. In binary regression analysis, which assessed various predictors on the likelihood of having hypercapnia, it was found that BMI (OR: 1.313, 95% CI: 1.048-1.646, = 0.018) and FVC (OR: 0.913, 95% CI: 0.845-0.986, = 0.020) were the major determinants of hypercapnia in OS patients.
CONCLUSIONS
Hypercapnic OS patients were more obese and sleepy and presented worse respiratory function in wakefulness and sleep hypoxia characteristics compared with normocapnic OS patients.
PubMed: 38929821
DOI: 10.3390/jpm14060600 -
Journal of Personalized Medicine Jun 2024Current United States Preventive Services Task Force (USPSTF) recommendations include routine screening for breast, cervical, colorectal, and lung cancer; however, two...
Current United States Preventive Services Task Force (USPSTF) recommendations include routine screening for breast, cervical, colorectal, and lung cancer; however, two out of every three cancer cases occur in other indications, leading to diagnoses in advanced stages of the disease and a higher likelihood of mortality. Blood-based multi-cancer early detection (MCED) tests can impact cancer screening and early detection by monitoring for multiple different cancer types at once, including indications where screening is not performed routinely today. We conducted a survey amongst healthcare providers (HCPs), payers, and patients within the U.S. health system to understand the current utilization of cancer screening tests and the anticipated barriers to widespread adoption of blood-based MCED tests. The results indicated that the community favors the adoption of blood-based MCED tests and that there is broad agreement on the value proposition. Despite this recognition, the survey highlighted that there is limited use today due to the perceived lack of clinical accuracy and utility data, high out-of-pocket patient costs, and lack of payer coverage. To overcome the hurdles for future widespread adoption of blood-based MCED tests, increased investment in data generation, education, and implementation of logistical support for HCPs will be critical.
PubMed: 38929814
DOI: 10.3390/jpm14060593 -
Journal of Personalized Medicine May 2024Inflammation-related parameters serve as pivotal indicators in the prognosis and management of lung cancer. This retrospective investigation aimed to explore the...
Inflammation-related parameters serve as pivotal indicators in the prognosis and management of lung cancer. This retrospective investigation aimed to explore the relationship between inflammatory markers and diverse clinical variables in non-small-cell lung cancer patients. A cohort of 187 individuals undergoing elective lobectomy for lung cancer was retrospectively analyzed, spanning an 11-year data collection period. Six inflammation ratios derived from complete peripheral blood counts were assessed. Significantly elevated levels of neutrophil-to-lymphocyte ratio (NLR) ( = 0.005), platelet-to-lymphocyte ratio (PLR) ( = 0.001), Aggregate Index of Systemic Inflammation (AISI) ( = 0.015), Systemic Inflammation Response Index (SIRI) ( = 0.004), and Systemic Immune Inflammation Index (SII) ( = 0.004) were observed in patients with advanced T stages. Significantly, elevated values ( < 0.05) of these parameters were observed in the study's smoker patients compared to non-smokers. A statistically significant correlation was identified between the NLR parameter and tumor size ( = 0.07, r = 0.204), alongside a significant elevation in SIRI ( = 0.041) among patients experiencing postoperative complications. Inflammatory biomarkers emerge as invaluable prognostic indicators for patients with non-small-cell lung cancer, offering potential utility in forecasting their prognosis.
PubMed: 38929773
DOI: 10.3390/jpm14060552