Routine Laboratory Research Articles

P-641. Distinct Cytokine Profiles in Severe Community-acquired Pneumonia and Metabolic Dysfunction-associated Steatotic Liver Disease

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been identified as a risk factor for severe community-acquired pneumonia (sCAP) outcomes. While MASLD is associated with chronic systemic inflammation, cytokine responses in patients with sCAP and MASLD have not been characterized. The aim of this study was to analyze differences in concentrations and kinetics of cytokines in sCAP patients with and without MASLD. Methods A prospective cohort pilot study included patients hospitalized with sCAP defined according to IDSA criteria. Upon admission, clinical and laboratory data were collected, and liver fibroelastography was performed to determine the presence of liver fibrosis and steatosis. Serum concentrations of 13 cytokines (IL-4, IL-2, CXCL10, IL-1β, TNF-α, CCL2, IL-17A, IL-6, IL-10, IFN-γ, IL-12p70, TGF-β1 and IL-8) were analyzed using a multiplex bead-based assay by flow cytometry at admission and on day 5 of hospitalization. Results Thirty-eight patients (26 males, median age of 69, [IQR 61-79] years) with sCAP (SOFA 3 [IQR 2-4], PaO2/FiO2 186 [IQR 150-241]) were included. Of them, 18 (47.4%) had MASLD. There were no differences in age, sex and baseline disease severity between the groups. Patients with MASLD more frequently had components of metabolic syndrome. Etiology was identified in 66%, most commonly influenza (50%) and S. pneumoniae (18%). There were no differences in routine laboratory findings at admission, except for lactate, urea, AST, ALT and LDH which were higher in the MASLD group. While at admission we observed no differences in cytokine concentrations, on the 5th-day patients with MASLD had significantly higher concentrations of CXCL10, IL-10, TNF-α, and lower TGF- β1. Both groups had similar cytokine kinetics with significant decreases in CXCL10, CCL2, IL-10, IL-8 and IL-6. However, distinct temporal changes were observed for TGF-β1 and IL-2 which increased only in patients without MASLD. Conclusion In conclusion, MASLD is associated with distinct cytokine profiles and kinetics in sCAP. A better understanding of cytokine changes could potentially help elucidate the complex and aberrant immune responses in MASLD patients during sCAP. Disclosures All Authors: No reported disclosures

P-2097. Genomic basis of Oxacillin- and Cefoxitin-Susceptible PBP2a-Positive Staphylococcus aureus

Abstract Background Methicillin-resistance Staphylococcus aureus (MRSA) is resistant to all ß-lactam antibiotics except for the fifth-generation cephalosporin drug, ceftaroline. The mecA gene, which encodes an alternative penicillin-binding protein, PBP2a, is responsible for the high-level resistance to methicillin. However, mecA positive, oxacillin- and cefoxitin susceptible MRSA has been reported, with limited understanding of the genomic basis behind this contradictory phenomenon. Here, we studied the molecular base of a “stealth” MRSA from clinical specimen. Methods A MRSA isolate was routinely isolated from a deep wound specimen, which was positive for PBP2a by lateral flow assay but negative for cefoxitin screen test and susceptible to oxacillin (MIC of 0.5 ug/ml) by VITEK 2 AST-GP75 card. It was also susceptible to cefoxitin using disk diffusion method (diameter of 26 mm). The “stealth” MRSA isolate was sequenced on illumina NovaSeq 6000 platform using 150 bp paired end sequencing. Bacteria genome was assembled and annotated using pipelines on BV-BRC (https://www.bv-brc.org/). Results Genomic sequencing revealed a point mutation (G to A) in the mecA gene resulting in a Gly599Ser substitution located in the transpeptidase domain of PBP2a, which is close to the active site of Ser403 on the 3D structure of the protein. Additionally, an insertion in the methicillin resistance regulatory sensor-transducer mecR1 gene was identified, resulting in a frameshift mutation, and predicted to cause premature termination. However, the sequence of frame shift mutation in mecR1 has been described and was not associated with reversed cefoxitin susceptibility. Therefore, the point mutation in mecA gene is most likely responsible for loss of function of PBP2a, and lead to susceptible cefoxitin and oxacillin results despite a positive PBP2a reaction. Conclusion Whole genome sequencing is valuable to understand the genomic basis of unusual phenotypic testing results. The reversion of “stealth” MRSA strain to a high-level oxacillin- and cefoxitin-resistant strain has been reported, which highlights the importance of considering tests for mecA or PBP2a in routine laboratory practice to avoid the risk of missing such strains. Disclosures All Authors: No reported disclosures

P-471. Clinical and Laboratory Characteristics of the Stockholm HTLV Cohort

Abstract Background The prevalence of HTLV infection in Sweden is presumed to be low, however the impact of demographic changes during the last 20 years on HTLV prevalence is unknown. In our study we describe clinical and laboratory characteristics of patients with HTLV -infection followed at our outpatient clinic at Karolinska University Hospital. Methods The clinical and laboratory data has been extracted from medical records of patient with HTLV infection between 2000-2024. We established a database which included demographics, mode of transmission, proviral HTLV load (PVL), occurrence of HTLV-1 associated myelopathy/tropical spastic paraparesis and Adult T cell leukemia (HAM/TSP and ATL), comorbidities and immunological and routine laboratory markers. Results We identified 101 patients with HTLV infection followed at our site (80% HTLV-1, 20% HTLV-2). Fifty-tree percent (n=54) were women. The average age in the cohort was 53,6 years (23-81). Twenty-nine percent (n=29) of the patients were born in Sweden, while the rest had other countries of origin (35% Middle east; 17% South America; 11% Africa ). HTLV infection was predominantly diagnosed through contact testing (34%), blood donor screening (32%), and pre-in vitro fertilization screening (32%), while clinical symptom investigation accounted for 12% of cases. Eleven individuals were HIV positive and predominantly co infected with HTLV-2. Of note, within the subset of patients born in Sweden, we identified four cases of mother-to-child transmission (MTCT) of HTLV. Until January 2024 ten individuals (10%) were diagnosed with HAM/TSP and two individuals with ATL. Patients with HAM/TSP had a higher average PVL as compared to the rest of the cohort (20,9% vs 7,8%). Furthermore, we conducted a quantitative analysis of regulatory T-cells in 26 HTLV-1 infected patients in peripheral blood using flow cytometry. Fifteen patients (58%) had elevated T-reg percentage (ranging from 12% to 51%) and higher PVL. Notably all three HAM/TSP patients were in the elevated T reg group. Conclusion In our cohort, we report a high percentage of patients with HAM/TSP and ATL. Notably, we found four cases of MTCT in patients born in Sweden. We also found a higher abundance of regulatory T-cells in the patient’s group with higher PVL and more prevalent occurrence of symptoms. Disclosures All Authors: No reported disclosures

Multi-level Factors to Build Confidence and Support in Active Surveillance for Low-Risk Prostate Cancer: A Qualitative Study.

Active surveillance (AS) is the guideline-recommended treatment for low-risk prostate cancer and involves routine provider visits, lab tests, imaging, and prostate biopsies. Despite good uptake, adherence to AS, in terms of receiving recommended follow-up testing and remaining on AS in the absence of evidence of cancer progression, remains challenging. We sought to better understand urologist, primary care providers (PCPs), and patient experiences with AS care delivery to identify opportunities to improve adherence. A qualitative study involving patients, PCPs, and urologists with experience of AS. PCPs (19), urologists (15), and patients (15) in Michigan. Participants were recruited through a statewide quality improvement collaborative. Semi-structured interviews were conducted virtually from June 2020 to April 2021. The Theoretical Domains Framework and the Behavior Change Wheel's Capability, Opportunity, and Motivation model guided interviews and coding. Thematic analysis was used to identify shared perspectives on AS care delivery. Three main themes emerged from the PCP, urologist, and patient data collected related to AS care delivery that were needed to improve AS adherence: (1) building patient confidence in AS by leveraging provider roles and expertise and creating connection through communication across the care team and with patients; (2) building confidence in AS through psychosocial support by involving families and peers, and addressing anxiety and uncertainty; (3) building AS support within healthcare processes and electronic health record systems. These themes reflect opportunities for interventions at the care team, community (family and peers), and health system levels that could better support individualized care and overcome challenges to AS adherence through team-based approaches.

Alkaline phosphatase of late pregnancy promotes the prediction of adverse birth outcomes.

Adverse birth outcomes (ABO), such as preterm birth (PTB), small and large for gestational age (SGA/LGA), can compromise both the short- and long-term health of mothers and their foetuses. The purpose of this observational study was to investigate the association between maternal serum alkaline phosphatase (ALP) levels in late pregnancy and the risk of ABO, and to evaluate its predictive value of maternal ALP levels for ABO in women with singleton pregnancies. A total of 11 853 consecutive pregnant women underwent hepatic and renal function tests, lipid profile assessments, ALP and high-sensitivity C-reactive protein levels measurements upon admission for labour. Their clinical perinatal parameters and outcomes were also analysed. The prevalence of PTB, SGA, and LGA in this study was 7.2% (n = 849), 8.9% (n = 1053), and 15.6% (n = 1844), respectively. With increasing quartiles of maternal serum ALP levels, the foetal gestational age increased by 0.58 weeks (95% confidence interval (CI) = 0.50-0.66), 0.78 weeks (95% CI = 0.70-0.86), and 0.98 weeks (95% CI = 0.90-1.06), respectively, and the birth weight increased by 62.91 g (95% CI = 43.96-81.86), 91.54 g (95% CI = 72.41-110.67), and 117.92 g (95% CI = 98.18-137.67), respectively. Compared to women in the bottom quartile of ALP, those in the top quartile had a lower risk of PTB (adjusted odds ratio (OR) = 0.14; 95% CI = 0.11-0.18), a lower risk of SGA (adjusted OR = 0.65; 95% CI = 0.53-0.80), and a higher risk of LGA (adjusted OR = 1.92; 95% CI = 1.62-2.28). Sensitivity analyses conducted among individuals without advanced maternal age, obesity, multiparity, pregnancy complications, and PTB (for SGA/LGA) validated the consistency of these results. More importantly, adding ALP to the established model significantly increased the area under the curve (AUC) for predicting adverse birth outcomes: for PTB, the AUC increased from 0.761 to 0.809 (P < 0.001); for SGA, it increased from 0.754 to 0.759 (P = 0.014); and for LGA, it increased from 0.750 to 0.755 (P < 0.001). Maternal serum ALP levels in late pregnancy are significantly associated with the risk of ABO. When combined with clinical characteristics and routine laboratory results, ALP has incremental predictive value for ABO, particularly for PTB.

P0761 Patient-reported outcomes are associated with calprotectin levels in post-IPAA patients

Abstract Background Patient-reported outcome measures (PROMs) in inflammatory bowel disease (IBD), such as the Short IBD Questionnaire (SIBDQ)1, assess IBD impact on patients' quality of life (QoL). We aimed to validate the SIBDQ in patients with ulcerative colitis (UC) who underwent ileal pouch-anal anastomosis (IPAA) surgery and to correlate disease activity with QoL. Methods This prospective, observational study recruited patients with UC post-IPAA attending a comprehensive pouch clinic at a tertiary referral center (Rabin Medical Center). Upon each visit, patients completed the SIBDQ and underwent routine clinical and laboratory assessments, including blood and fecal tests. Fecal calprotectin (FCP) was chosen as a marker of active pouch disease2. Spearman’s rank correlation was used to evaluate the relationship between FCP levels and PROMs. Wilcoxon’s rank sum test was used to compare different groups. Results The study included 166 patients with UC with 1,016 visits (median age 50 years, IQR 37–63.5; 56.6% female). SIBDQs were completed in 941 (93%) visits. A significant negative correlation was noted between FCP levels and total SIBDQ scores (p&amp;lt;0.001). In specific SIBDQ domains, correlations between FCP and fatigue (p=0.005), depression (p=0.04), anxiety (p=0.004), and urgency (p&amp;lt;0.001) were noted as well (Figure 1). Additionally, FCP levels correlated with daily bowel movements (BMs) (p&amp;lt;0.001), which, in turn, correlated with total SIBDQ score (p&amp;lt;0.001). In patients with chronic pouch inflammation (n=71, 42.7%; 327 visits), FCP levels were significantly higher (548.6 vs. 328.3 μg/g, p&amp;lt;0.001) and SIBDQ scores significantly lower (47.6 vs. 54.5, p&amp;lt;0.001) compared to the rest of the cohort. Notably, among those with chronic complications receiving biologic therapy, FCP levels decreased (461.6 vs. 593.9 μg/g, p=0.009), and SIBDQ scores improved (45.8 vs. 49.8, p=0.001). Conclusion Elevated FCP levels correlate with lower SIBDQ scores, suggesting that active pouch inflammation may affect patient’s quality of life. Specific PROMs, such as fatigue, depression, anxiety, and urgency, were also associated with FCP levels, highlighting them as key areas affected by inflammation. Targeting inflammatory activity, such as by biologic therapy, was associated with improved SIBDQ scores. These correlations suggest that the burden of inflammation may contribute to different PROMs and overall well-being in patients with a pouch. This emphasizes the importance of the patient’s quality of life when aiming for inflammation control, further highlighting the alignment between disease activity and overall well-being in patients with pouch.

P0425 Factors Associated with Biopsy-Proven Cuffitis in Ulcerative Colitis Patients Following Colectomy with Ileal Anal-Pouch Anastomosis

Abstract Background Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment in patients with refractory/complicated ulcerative colitis (UC). Inflammation of the small rectal remnant below IPAA lines (“cuff”) is designated cuffitis. Despite its clinical significance and characteristic endoscopic and histologic features, risk factors are vague. This study aimed to decipher demographic, disease, and surgery-related risk factors for histologically proven cuffitis. Methods In a comprehensive pouch clinic at a tertiary referral center (Rabin Medical Center), consenting patients were followed prospectively, with routine clinical, laboratory, and endoscopic evaluations. Patients after IPAA due to UC having≥1 cuff biopsy during follow-up were included. Histological cuff samples were scored based on the validated NANCY index. Cuffitis, the primary outcome, was defined as evidence of moderate-to-severe histologic inflammation (NANCY score 3-4). Univariate Cox models were used to assess hazard ratios (HRs) of various factors with the occurrence of cuffitis. Results Of 400 patients followed at the pouch clinic, 182 consented to prospective follow-up, and 116 underwent cuff biopsy, each having a median of 2 biopsies. Most patients had histological evidence of moderate-to-severe cuffitis (n=76, 65.5%). Significant associations with cuffitis included disease duration ≤10 years before surgery (HR 15.4, 95%CI; 4.0-59.1, p&amp;lt;0.001); body mass index ≤ 18.5 (HR 3.83, 95%CI; 1.75-8.4, p&amp;lt;0.001); Arab descent (HR 3.2, 95%CI; 1.1-9, p=0.03); immediate postoperative complications (HR 2.0, 95%CI; 1.24-3.2, p=0.004); strong association with pre-operative biologic treatment was observed, with a single biologic (anti-TNF 90%) used before colectomy having a HR of 5 (95%CI;2.6-9.7, p&amp;lt;0.001) and multiple biologics having a HR of 14 (95%CI; 6.1-34, p&amp;lt;0.001). Interestingly, refractory UC as the indication for IPAA (vs dysplasia) was not independently associated with an increased risk of cuffitis. Conclusion Several demographic, disease, and surgery-related factors associated with post-IPAA cuffitis were identified. These may be incorporated into decision-making processes. Furthermore, closer postoperative follow-up may be warranted in specific patient subgroups. ese patients may benefit from closer post-operative follow-up.

P0256 Histologically-proven isolated cuffitis and quality of life among patients with ileoanal pouch

Abstract Background Patients with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) may develop inflammation of the ileal pouch (pouchitis), rectal cuff (cuffitis), or both. We aimed to evaluate how isolated cuffitis impacts patients' quality of life (QoL). Methods In a comprehensive pouch clinic at a tertiary referral center (Rabin Medical Center), consenting patients were followed prospectively, with routine clinical, laboratory, endoscopic, and QoL evaluations. Patients undergoing IPAA due to UC and having ≥1 cuff biopsy during follow-up were included. Patients with isolated cuffitis (cuff inflammation but no pouch inflammation) were compared to patients with isolated pouchitis (inflammation of the pouch with a normal cuff). Pouch endoscopy findings were defined based on the Pouchitis Disease Activity Index (PDAI) endoscopic and histologic subscores. Cuff endoscopy findings were defined based on Mayo endoscopic subscore and NANCY histological index. Cuffitis was defined as evidence of moderate-to-severe histologic inflammation (NANCY score 3-4). Results The cohort included 116 patients (median age 50 years, IQR 42-64; 60% females, n=68) who underwent 250 endoscopies (median 2, range 1-3). Isolated cuffitis (Mayo≥2) was diagnosed in 7 endoscopies, and isolated pouchitis (PDAI&amp;gt;2) in 33. Histologically, isolated cuffitis was detected in 39 biopsies, and isolated pouchitis in 72 biopsies. Patients with isolated cuffitis had higher body mass index (27 [23–29] vs. 23 [21–27], p=.03). Inflammatory markers, including C-reactive protein (0.61 [0.32–1.27] vs. 0.64 [0.31–1.03], p=.98) and fecal calprotectin (135.5 [53.25–347.5] vs. 276.0 [131.0–553.0], p=.21), were similar. Both groups had comparable daily bowel movements (BMs); 39% of patients with isolated cuffitis vs. 42% of those with isolated pouchitis had &amp;gt;10 BM/day (p=.79). Bristol stool scale scores 6-7 were reported in 94% of patients with isolated cuffitis compared to 76% with pouchitis (p=.04). Both groups had similar PDAI clinical sub-scores (p=.98). Patients with isolated cuffitis were more likely to report overall (22% vs. 7%, p=.08) and current (31% vs. 16%, p=.13) poor well-being. QoL scores were comparable: median Short Inflammatory Bowel Disease Questionnaire (SIBDQ) 46.5 vs. 50.5, (p=.53) and IBD-Control score of 10.0 vs. 7.0, (p=.6). Conclusion Cuff histology reveals higher rates of inflammation than endoscopy alone. Patients with histologically-proven isolated cuffitis and a normal pouch experience a negative impact on QoL as those with an inflamed pouch only. These findings suggest that greater attention to identifying cuffitis and effective management are required.

P1313 Gut microbiota therapy improves outcomes in inflammatory bowel disease

Abstract Background Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a long-term condition characterized by inflammation of the gut. Research has shown that disruption of the gut microbiota, known as dysbiosis, plays an important role in the disease. While current treatments focus on controlling inflammation, many patients continue to experience symptoms or side effects. This study explores the effectiveness of a new therapy aimed at restoring the balance of gut microbes and improving disease outcomes. Methods This study included 120 adults with IBD, randomly divided into two groups: one received standard care, and the other received a combination of prebiotics, probiotics, and dietary adjustments targeting gut bacteria. The trial lasted 12 weeks, with assessments at the start, 6 weeks, and 12 weeks. Prognosis was assessed through upper gastrointestinal endoscopy (including esophagogastroduodenoscopy) and colonoscopy to evaluate disease extent, detect complications, and monitor gastrointestinal changes. Postoperative complications, clinical symptoms, and routine lab tests (CRP and IL-6) were used to assess outcomes. Statistical tests compared clinical and endoscopic results between the groups. Results Patients who received the microbiota-targeted therapy showed significant improvement compared to the standard care group. Disease scores decreased notably (Harvey-Bradshaw Index reduced by 3.9 points and Mayo Score by 3.2 points, both p &amp;lt; 0.01). Blood markers of inflammation also dropped, with CRP levels falling by 42% and IL-6 by 38% (both p &amp;lt; 0.05).Additionally, upper gastrointestinal endoscopy (including esophagogastroduodenoscopy) and colonoscopy were used to assess the condition of the gastrointestinal tract and evaluate disease improvement. Postoperative complications, changes in clinical symptoms, and routine test results also helped in determining the treatment outcome. The therapy was well tolerated by patients, with no major side effects reported. Conclusion This study highlights the promising potential of gut microbiota therapy as a safe and effective approach for improving symptoms and reducing inflammation in IBD. By restoring balance to the gut microbiota, this therapy targets a critical factor in the disease process. The positive outcomes observed in this trial pave the way for future research into the integration of microbiota-based treatments as part of comprehensive IBD management strategies. Continued investigation in larger, long-term studies will be crucial to further validate these findings and explore the potential of microbiota-targeted therapies for achieving sustained remission and improving overall patient outcomes.

Rapid diagnostic testing combined with an immediate infectious disease consultation increases the rate of septic intensive care unit patients on targeted antibiotic therapy.

To evaluate the impact of rapid diagnostic testing (RDT) combined with immediate infectious disease (ID) consultation on the treatment of septic patients with positive blood cultures in intensive care units in a setting without 24/7 service. Adult ICU patients in a tertiary care hospital with positive blood cultures were included from January 2019 to December 2020. The control group underwent routine laboratory testing, and for the intervention group, RDT was applied with immediate ID consultation. In 77 out of the 91 patients in the intervention group, the pathogen was identified by RDT. Regarding antimicrobial susceptibility testing (AST), genotypic testing (ePlex®) was successful for Gram-positive cocci, but inadequate for Gram-negative rods. Phenotypic resistance testing with the Accelerate PhenoTest® took too long to be successfully integrated into the intervention. Adaptation of empirical antibiotic therapy was recommended for 72.7% of the patients. Adherence to the ID consultation post-RDT results was high at 82.3%. In the control group, adaptation of the initial antibiotic therapy would have been recommended for 81.8% of patients, if the species identification had been available. Overall adherence to the local antibiotic therapy guideline for sepsis was significantly lower in the control than in the intervention group (27.8% versus 89.3%, p<0.001). Integration of an RDT system in the microbiological workflow for septic patients in ICU combined with a standardized ID intervention led to a significantly higher percentage of adequate antimicrobial treatment and greater adherence to local antibiotic therapy recommendations, even in a setting where 24/7 service is not available.

Bacterial Diversity in Native Heart Valves in Infective Endocarditis.

Background: Infective endocarditis (IE) is an infectious disease caused by the hematogenous dissemination of bacteria into heart valves. Improving the identification of pathogens that cause IE is important to increase the effectiveness of its therapy and reduce the mortality caused by this pathology. Methods: Ten native heart valves obtained from IE patients undergoing heart valve replacements were analyzed. Bacterial invasion in the heart valves was studied by Gram staining of histological sections. Histopathological changes accompanied with bacterial invasion were studied by immunohistochemical analysis of pan-leukocyte marker CD45, platelet marker CD41, and neutrophil myeloperoxidase. The taxonomic diversity of the bacteria was analyzed using 16S rRNA metabarcoding. Results: Gram staining of the histological sections revealed bacterial cells localized on the atrial surface at the leaflet's free edge or on the ventricular surface at the leaflet's base within fibrin deposits in only three of the studied heart valves. Bacterial colonies were co-localized with microthrombi (CD41+ cells) containing single leucocytes (CD45+ cells), represented by segmented neutrophils. As a result of 16S rRNA metabarcoding, we detected the following bacterial genera: Pseudomonas (70% of the studied heart valves), Roseateles (60%), Acinetobacter (40%), Sphingomonas (40%), Enterococcus (30%), Reyranella (20%), Sphingobium (20%), Streptococcus (20%), Agrobacterium (20%), Ralstonia (10%), and Bacillus (10%). Conclusions: A number of opportunistic microorganisms that could not be detected by routine laboratory tests and were not eliminated during antibiotic therapy were identified in the IE-affected heart valves. The obtained results show the importance of 16S rRNA metabarcoding of heart valves removed due to IE not only as an independent diagnostic method but also as a highly accurate approach that complements routine tests for pathogen identification.

Prediction of Prostate Cancer From Routine Laboratory Markers With Automated Machine Learning.

In this study, we attempted to select the optimum cases for a prostate biopsy based on routine laboratory test results in addition to prostate-specific antigen (PSA) blood test using H2O automated machine learning (AutoML) software, which includes many common machine learning algorithms. The study included 737 patients (46-88 years old). Routine laboratory measurements were used to train machine learning models using H2O AutoML. We created a model that classifies prostate biopsy results as malignant or benign. The performance of the best model was evaluated using the area under the receiver operating characteristic curve (AUC), log-loss metric, F1 score, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity. The model's performance was evaluated through the SHapley Additive exPlanations (SHAP) analysis feature-based interpretation method applied to comprehend the machine learning model. The gradient boosting machine model was the most successful. The best result was obtained in the model with 11 parameters, including PSA, free PSA, free PSA to PSA, hemoglobin, neutrophils, platelets, neutrophil-to-lymphocyte ratio (NLR), glucose, platelet-to-lymphocyte ratio (PLR), lymphocytes, and age. The AUC of this model was 0.72, the specificity was 0.84, the PPV was 0.65, the NPV was 0.69, and the accuracy was 0.68. Our results suggest that adding only routine laboratory parameters to the PSA test and developing machine learning algorithms can help reduce the number of unnecessary prostate biopsies without overlooking the diagnosis of PCa.

A clinical algorithm to identify people with the glucose-6-phosphate dehydrogenase p.Val68Met variant at risk for diabetes undertreatment.

To develop an algorithm using routine clinical laboratory measurements to identify people at risk for systematic underestimation of glycated hemoglobin (HbA1c) due to p.Val68Met glucose-6-phosphate dehydrogenase (G6PD) deficiency. We analyzed 122,307 participants of self-identified Black race across four large cohorts with blood glucose, HbA1c, and red cell distribution width measurements from a single blood draw. In UK Biobank, we used recursive partitioning to develop criteria for possible and likely G6PD deficiency. We validated the algorithm in NIH All of Us, Vanderbilt BioVU, and the Million Veterans Program. In Vanderbilt's Synthetic Derivative, we created a cohort of 48,031 participants with type 2 diabetes and no genetic data to test whether predicted risk for G6PD deficiency was associated with incident diabetic retinopathy. G6PD deficiency predictions in hemizygous males showed precision/recall of 31%/81% for possible and 81%/10% for likely deficiency. In homozygous females, precision/recall was 6%/76% for possible and 34%/13% for likely deficiency. Diabetic patients with predicted possible deficiency demonstrated 1.4-fold higher 20-year retinopathy rates (14.3% vs 11.2%, P=0.003). We report a simple clinical algorithm that enables healthcare systems to identify people who may benefit from G6PD genotyping and glucose-based diabetes monitoring.

Blood pressure control with active ultrafiltration measures and without antihypertensives is essential for survival in hemodiafiltration and hemodialysis programs for patients with CKD: a prospective observational study

BackgroundHigh blood pressure is a prevalent condition in patients with chronic kidney disease on hemodialysis. Adequate control of high blood pressure is essential to reducing deaths in this group. The present study aimed to observe mortality prospectively in a group of patients in hemodialysis and hemodiafiltration programs in whom the use of antihypertensives was optimized with the point-of-care dry weight (POC-DW) technique.MethodsThe present observational, prospective study was carried out at the Pafram hemodiafiltration unit in Morona Santiago, Ecuador, and the hemodialysis unit of the Fundación Renal del Ecuador in Guayaquil, Ecuador, from August 2019 to December 2023. Patients who were receiving hemodiafiltration were included. Weight was optimized with POC-DW for eight weeks. In Group 1, patients whose use of antihypertensive drugs was not required to control systolic blood pressure with a value less than 150 mmHg predialysis, less than 130 mmHg postdialysis, and a peridialytic blood pressure (defined as post-HD minus pre-HD SBP) between 0 and − 20 mmHg were analyzed. In Group 2, patients who required antihypertensive drugs for not meeting the aims of systolic blood pressure were included. The variables included clinical, demographic, mortality, description of the treatment, and routine laboratory tests in dialysis programs. The sample was nonprobabilistic. Survival analysis was performed for the study groups. The log-rank test (Mantel-Cox) was used for survival comparisons.ResultsThe study included 106 patients. Optimal blood pressure control without antihypertensive treatment was achieved in 52 patients (49.1%) (Group 1). In 54 patients (50.9%), antihypertensive agents were required (Group 2). There was more significant mortality in the group that received antihypertensives: 11 patients in group 1 (21.2%) versus 25 patients in group 2 (46.3%) (P = 0.005). Survival was more significant in group 1, with an HR of 2.2163 (1.125–4.158) (P = 0.0243).ConclusionIn hemodiafiltration and hemodialysis programs, blood pressure control with active ultrafiltration measures and without using antihypertensives is essential for survival in patients with CKD.

EVALUATION OF THE APPLICABILITY OF THE O.K.N.V.I. RESIST-5 AND THE KPC&amp;amp;MBL&amp;amp;0XA-48 DISK TESTS IN A ROUTINE MICROBIOLOGY LABORATORY

Background: The global spread of carbapenemase-producing Enterobacterales (CPE) and the increasing emergence of clinical Enterobacterales harboring multiple carbapenemases of different molecular classes have prioritized the use of rapid molecular detection methods in routine microbiology laboratories. The aim of this study was to evaluate the applicability of the immunochromatographic O. K.N.V.I. RESIST-5 and the KPC&amp;MBL&amp;0XA-48 disc tests in a clinical microbiology laboratory. Material and methods: The tests were performed with 50 CPE belonging to 8 species and producing 7 molecularly characterized carbapenemases. Six of these isolates carried two different carbapenemases. To assess the specificity of the assays, 18 non-carbapenemase-producing but carbapenem-resistant Enterobacterales (non-CP CRE) were also included. Both tests were performed from a common overnight culture on Mueller-Hinton agar with inoculum harvested around an ertapenem disk. Results: The O.K.N.V.I. RESIST-5 correctly detected all 56 carbapenemases, including KPC-2 in Klebsiella pneumoniae; OX-48 in Serratia marcescens, Citrobacter freundii, Enterobacter hormaechei and K. pneumoniae; NDM-1 in Escherichia coli, Morganella morganii, E. hormaechei, C. freundii, S. marcescens and K. pneumoniae; VIM-1 in Proteus mirabilis; VIM-4 in C. freundii and S. marcescens; VIM-86 with and without NDM-1 in Providencia stuartii, and NDM-5 with and without OXA-232 in K. pneumoniae. The KPC&amp;MBL&amp;0XA-48 disc tests correctly confirmed KPC, OX-48-like and most MBL except VIM in P. mirabilis. Furthermore, the combination disc tests failed to detect OXA-48-like in pairs with MBL in K. pneumoniae. Conclusions:The O.K.N.V.I. RESIST-5 multiplex lateral assay is an excellent test for rapid diagnostic of CPE in routine microbiology laboratories. It is easy to handle and provides results with 100% sensitivity and specificity when an inoculum around ertapenem disc from routine antibiogram was used.

Diagnostic Markers of Severe COVID-19 and Community-Acquired Pneumonia in Children From Southern India.

COVID-19 severely impacts children in India, with many developing severe pneumonia or multisystem inflammatory syndrome (MIS-C). Concurrently, non-COVID-19 respiratory viruses causing community-acquired pneumonia (CAP) have resurged. These conditions present similarly, challenging accurate diagnosis. This study aims to compare inflammatory markers and clinical parameters in children with severe COVID-19 pneumonia, non-COVID-19 CAP, and COVID-associated MIS-C. We assessed 12 mediators in serum from 14 children with severe COVID-19 pneumonia, 16 with severe non-COVID-19 CAP, and 9 with MIS-C. Clinical characteristics and routine laboratory findings at admission were recorded. Children with MIS-C had significantly higher levels of IL-1RA, IL-8, and TNF compared with those with severe COVID-19 pneumonia; and higher levels of CCL2, HGF, M-CSF, and IL-8 compared with severe non-COVID-19 CAP. GROα levels tended to be higher in severe COVID-19 pneumonia. Clinical presentations were similar, but MIS-C patients had distinct laboratory findings, including lower platelet counts and albumin levels, and higher creatinine and liver enzyme levels. MIS-C exhibited a unique inflammatory profile. IL-8 emerged as a potential biomarker for MIS-C, while increased GROα levels in severe COVID-19 pneumonia merit further exploration. Combining inflammatory markers with routine laboratory parameters may improve the diagnosis and differentiation of these conditions, enhancing patient management.

Issues in the diagnosis of pneumonia in elderly patients

In elderly patients, the onset of pneumonia is often subtle and typical respiratory symptoms are less common. Instead, non-specific presentations such as altered mental status and loss of appetite should be closely monitored. The sensitivity of chest X-rays and routine laboratory tests is often low, so a comprehensive assessment including risk factors is required. The presence of multiple comorbidities, including chronic respiratory disease, cardiovascular disease, and diabetes mellitus, is prevalent in this population and complicates early diagnosis. Polypharmacy further adds to the diagnostic and therapeutic challenges. Due to difficulties in specimen collection, high risks associated with invasive testing and atypical pathogen distributions, conventional microbiological detection methods often fail to meet clinical needs. Nucleic acid testing techniques, such as metagenome next-generation sequencing, offer a rapid and sensitive alternative for detecting a wide range of pathogens, including those not identified by conventional methods, as well as rare, multiple, or mixed infections. This approach also has the advantage of not being influenced by prior antibiotic use, making it a crucial role in diagnosing pneumonia in the elderly. However, it is imperative to select appropriate and high-quality specimen types and to interpret the results accurately, taking into account the clinical context and indications for testing. Timely and precise diagnosis is essential to improve the prognosis of pneumonia in elderly patients.

Indirect determination of hemoglobin A2 reference intervals in Pakistani infants using data mining

BackgroundReference intervals (RIs) are crucial for distinguishing healthy from sick individuals and vary across age groups. Hemoglobinopathies are common in Pakistan, making the quantification of hemoglobin variants essential for screening. Direct RIs are established by measuring values from a healthy reference population, whereas indirect RIs, use statistical analysis of routine lab data to estimate values, making it feasible in settings where direct data is unavailable. Since Pakistan lacks locally established Hemoglobin A2 RIs for infants, this study aims to fill that gap using an indirect data mining method to improve diagnostic accuracy for hemoglobinopathies.MethodsIt was a retrospective observational study. Hemoglobin A2 measurements from all patients aged birth to 1 year between January 2015 and December 2022 were retrieved from the laboratory management system at Aga Khan University Hospital. The study population represented the entire geographical distribution of the country. Hemoglobin A2 was measured using the Bio-Rad Variant™ II analyzer. RIs were computed using an indirect KOSMIC algorithm, which assumes non-pathologic samples follow a Gaussian distribution after Box-Cox transformation.ResultsA total of 88,690 specimens were analyzed for HbA2. After excluding patients with multiple specimens, RIs were calculated for 22,713 infants, stratified into five age sub-groups. The 2.5th and 97.5th percentile results showed good agreement with RIs from Mayo Clinic Laboratories.ConclusionsThis study supports data mining as an alternative method for establishing HbA2 RIs, especially in resource-limited settings. The results are specific to the studied population, instrument, and reagent, and they elucidate the fluctuations in HbA2 synthesis with age. These intervals will enhance clinical decision-making based on HbA2 results.

Association of nutritional status indices with gastrointestinal symptoms in systemic sclerosis: a cross-sectional study

Gastrointestinal (GI) involvement is highly prevalent in systemic sclerosis (SSc) and significantly affects patient quality of life and clinical outcomes. This study investigates the potential of undernutrition scores, namely the Control of Nutritional Status (CONUT) score and the Prognostic Nutrition Index (PNI), in predicting GI involvement in patients with SSc. A total of 82 patients diagnosed with SSc were enrolled in this cross-sectional study. Participants were evaluated using the UCLA Scleroderma Clinical Research Consortium Gastrointestinal Tract 2.0 (UCLA GIT 2.0) tool, which assesses the severity of GI symptoms and their impact on health-related quality of life. Malnutrition was assessed using CONUT and PNI scores derived from routine laboratory parameters. The correlation between these malnutrition indices and the UCLA GIT 2.0 scores was analyzed to determine the predictive value of malnutrition in GI involvement. The study found that patients with higher CONUT scores, indicating malnutrition, had significantly higher total UCLA GIT 2.0 scores. A moderate positive correlation was observed between CONUT scores and total UCLA GIT 2.0 scores (r =.539; p <.01), while a negative correlation was found between CONUT scores and PNI (r = −.513; p <.01). These findings suggest that malnutrition, as measured by CONUT and PNI, is associated with greater GI involvement in SSc. This study shows that malnutrition indices such as CONUT and PNI in SSc patients, together with the UCLA GIT 2.0 score, may serve as usefull predictors of GI involvment in routine clinical practice.

Predictive Value of Complete Blood Count (CBC)-Derived Indices-C-Reactive-Protein-Albumin-Lymphocyteindex (CALLY), Glucose-to-Lymphocyte Ratio (GLR), Prognostic Nutritional Index (PNI), Hemoglobin, Albumin, Lymphocyte, Platelet (HALP), and Controlling Nutritional Status (COUNT)-on Body Composition Changes After Bariatric Surgery.

Obesity is linked to increased risks of cardiovascular disease, diabetes, and certain cancers. Bariatric surgery (BS) aids in weight management, significantly altering body composition. This study evaluates the predictive value of five complete blood count (CBC)-derived indices[C-reactive-protein-albumin-lymphocyte (CALLY), glucose-to-lymphocyte ratio (GLR), prognostic nutritional index (PNI), hemoglobin, albumin, lymphocyte, platelet (HALP), and controlling nutritional status (COUNT)]on body composition changes post-BS. A retrospective study was conducted on 240 patients undergoing BS atSina Hospital,Tehran, Iran. Indices were calculated using routine laboratory tests, and body composition changes were measured using bioelectrical impedance analysis at 3 and 6months post-surgery. RESULTS: Higher pre-surgical GLR values positively correlated with increased fat-free mass (FFM) (p = 0.005 1, p = 0.003 2), muscle mass (MM) (p = 0.011 1, p = 0.008 2), and total body water (TBW) (p = 0.005 1, p = 0.005 2) post-surgery.In contrast, higher PNI was negatively associated with changes in FM (p = 0.029 1, p = 0.015 2), FFM (p = 0.002 1, p = 0.018 2), TBW (p = 0.002 1, p = 0.015 2) and MM (p = 0.003 2), particularly after laparoscopic sleeve gastrectomy (LSG). Furthermore, there was a significant correlation between pre-surgical HALP score and changes in FFM (p = 0.002 1, p = 0.042 2), TBW (p = 0.002 1) and MM (p = 0.011 1, p = 0.041 2). In addition, the modified HALP score showed a more significant correlation compared to the HALP score to predict the changes FM (p = 0.002 1, p = 0.002 2), FFM (p = 0.001 1, p = 0.006 2), TBW (p = 0.001 1, p = 0.003 2) and MM (p = 0.001 1, p = 0.023 2) particularly, after 6months. Our findings suggest that pre-surgical assessment of GLR, PNI, and HALP indices may provide valuable insights into predicting changes in body composition after bariatric surgery. Specifically, these indices could serve as tools for tailoring preoperative nutritional strategies and post-surgical interventions. However, as this study is retrospective, further prospective research with longer follow-ups is required to validate these findings and evaluate their utility in clinical practice. 1 3months after metabolic bariatric surgery. 2 6months after metabolic bariatric surgery.