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Background Cardiac injury caused by iron overload is the leading cause of mortality and morbidity in patients with beta-thalassemia, owing to frequent blood transfusion, increased iron overload, and blood hemolysis. Objective This research aimed to assess several novel cardiac biomarkers in the blood samples of children and adult patients with beta-thalassemia major (βTM), along with their respective control groups. These biomarkers included endothelin 1 (ET-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), growth differentiation factor-15 (GDF-15), and renalase (RNLS). Methods This case-control study was done on 46 patients with βTM (23 children <18 years, and 23 adults ≥18 years) from the Genetic Hematology Center in Thi-Qar province, Iraq, and 42 comparable controls in 2 groups (21 for each group) in the period from February to April 2023. Results Levels of ET-1, NT-proBNP, ANP, GDF-15, RNLS, and ferritin were higher in the children and adults with βTM than in the control subjects. Conclusion Elevations of the novel cardiac biomarkers ET-1, NT-proBNP, ANP, GDF-15, and RNLS in the sera of children and adult patients with βTM when compared with comparable control subjects confirm that the majority of patients with βTM are at risk of cardiac and cardiovascular complications even when there are no obvious symptoms, especially in children, which gives suitable predictive biomarkers. [ABSTRACT FROM AUTHOR]

Objectives To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM). Methods Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls. Whole-body DXA and hand-grip dynamometer were used to measure muscle mass, grip strength and diagnose sarcopenia (EWGSOP2 criteria). Relationships between the results of strength in 12 muscles, functional tests, patient-reported disability, IMACS damage score, and history of the disease were assessed. The serum levels of potential molecular actors in the damage were measured. Results DXA and grip strength measurements took ≤20 min. Both muscle mass and grip strength were decreased in IM patients vs volunteers (−10% and −30%, respectively) with a dispersion that varied widely (interquartile range −24.3% to +7.8% and −51.3% to −18.9%, respectively). Muscle mass and grip strength were non-redundantly correlated (r up to 0.6, P  = 0.0001) with strength in 14 muscles (manual muscle test and hand-held dynamometer), functions (of limbs, respiratory and deglutition muscles), patient-reported disability, damage (extension and severity in muscular and extra-muscular domains) and blood levels of several myokines. Seven IM patients (17.5%) were sarcopenic. They had the worst damage, impaired functions, disability and history of severe myopathy. Decreased irisin and osteonectin levels were associated with sarcopenia (area under the curve 0.71 and 0.80, respectively). Conclusion DXA and hand-grip dynamometer are useful tools to assess damage in IM. Irisin and osteonectin may play a role in IM damage pathogenesis. [ABSTRACT FROM AUTHOR]

The aim of this literature review was to identify and provide a summary update on the validity and applicability of the most promising dietary biomarkers reflecting the intake of important foods in the Western diet for application in epidemiological studies. Many dietary biomarker candidates, reflecting intake of common foods and their specific constituents, have been discovered from intervention and observational studies in humans, but few have been validated. The literature search was targeted for biomarker candidates previously reported to reflect intakes of specific food groups or components that are of major importance in health and disease. Their validity was evaluated according to 8 predefined validation criteria and adapted to epidemiological studies; we summarized the findings and listed the most promising food intake biomarkers based on the evaluation. Biomarker candidates for alcohol, cereals, coffee, dairy, fats and oils, fruits, legumes, meat, seafood, sugar, tea, and vegetables were identified. Top candidates for all categories are specific to certain foods, have defined parent compounds, and their concentrations are unaffected by nonfood determinants. The correlations of candidate dietary biomarkers with habitual food intake were moderate to strong and their reproducibility over time ranged from low to high. For many biomarker candidates, critical information regarding dose response, correlation with habitual food intake, and reproducibility over time is yet unknown. The nutritional epidemiology field will benefit from the development of novel methods to combine single biomarkers to generate biomarker panels in combination with self-reported data. The most promising dietary biomarker candidates that reflect commonly consumed foods and food components for application in epidemiological studies were identified, and research required for their full validation was summarized. [ABSTRACT FROM AUTHOR]

Background Streptococci are a common cause of infective endocarditis (IE). We aimed to evaluate the performance of the HANDOC score to identify patients at high risk for IE and the Duke clinical criteria of the European Society of Cardiology (ESC; 2015 and 2023 versions) and the 2023 version from the International Society of Cardiovascular Infectious Diseases (ISCVID) in diagnosing IE among patients with streptococcal bacteremia. Methods This retrospective study included adult patients with streptococcal bacteremia hospitalized at Lausanne University Hospital. Episodes were classified as IE by the Endocarditis Team. A HANDOC score >2 classified patients as high risk for IE. Results Among 851 episodes with streptococcal bacteremia, IE was diagnosed in 171 episodes (20%). Among 607 episodes with non-β-hemolytic streptococci, 213 (35%) had HANDOC scores >2 points; 132 (22%) had IE. The sensitivity of the HANDOC score to identify episodes at high risk for IE was 95% (95% confidence interval [CI], 90%–98%), the specificity 82% (95% CI, 78%–85%), and the negative predictive value (NPV) 98% (95% CI, 96%–99%). 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria classified 114 (13%), 145 (17%), and 126 (15%) episodes as definite IE, respectively. Sensitivity (95% CI) for the 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria was calculated at 65% (57%–72%), 81% (74%–86%), and 73% (65%–79%), respectively, with specificity (95% CI) at 100% (98%–100%), 99% (98%–100%), and 99% (98%–100%), respectively. Conclusions The HANDOC score showed an excellent NPV to identify episodes at high risk for IE. Among the different versions of the Duke criteria, the 2023 Duke-ISCVID version fared better for the diagnosis of IE among streptococcal bacteremia. [ABSTRACT FROM AUTHOR]

Background Evidence about the clinical impact of rapid diagnostic tests (RDTs) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (B Cs) embedded within antimicrobial stewardship programs (ASPs) is unknown. Methods We performed network meta-analyses using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS), and time to optimal therapy. Results Eighty-eight papers were selected, including 25 682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The network meta-analyses showed a significant reduction in mortality associated with the use of RDT + ASP versus BC alone (odds ratio [OR], 0.72; 95% confidence interval [CI],.59–.87) and with the use of RDT + ASP versus BC + ASP (OR, 0.78; 95% CI,.63–.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP versus BC alone (OR, 0.91; 95% CI,.84–.98) whereas no difference in LOS was shown between any other groups. A reduced time to optimal therapy was shown when RDT + ASP was compared to BC alone (−29 hours; 95% CI, −35 to −23), BC + ASP (−18 hours; 95% CI, −27 to −10), and to RDT alone (−12 hours; 95% CI, −20 to −3). Conclusions The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC. [ABSTRACT FROM AUTHOR]

Background Clinicians variably obtain anaerobic blood cultures as part of sepsis evaluations in the neonatal intensive care unit (NICU). Our objective was to determine if anaerobic blood culture bottles yielded clinically relevant information by either recovering pathogens exclusively or more rapidly than the concurrently obtained aerobic culture bottle in the NICU. Methods A retrospective cohort study of blood cultures obtained from infants admitted to the NICU from August 01, 2015 to August 31, 2023. Standard practice was to inoculate 2 mL of blood divided equally between an aerobic and an anaerobic culture bottle. We analyzed positive blood cultures where both aerobic and anaerobic bottles were obtained and compared pathogen recovery and time to positivity between the bottles. Results During the study period, 4599 blood cultures were obtained from 3665 infants, and 265 (5.8%) were positive. Of these, 182 cultures were sent as aerobic–anaerobic pairs and recovered pathogenic organisms. Organisms were recovered exclusively from the anaerobic bottle in 32 (17.6%) cultures. Three organisms were obligate anaerobes; the rest were facultative anaerobes including Coagulase-negative staphylococci (40.6%), Escherichia coli (15.6%), and Staphylococcus aureus (15.6%). Cultures with exclusive recovery in the anaerobic bottle were more frequently obtained ≤3 days after birth, compared to other cultures (31.3% vs 15.3%, P  = .03). When both bottles recovered the pathogen (n  = 113), the anaerobic bottle had a shorter time to positivity in 76 (67.3%) cultures. Conclusions Including anaerobic culture bottles could lead to the identification of pathogens not recovered in the aerobic bottle, as well as earlier identification of pathogens. [ABSTRACT FROM AUTHOR]

Blood transfusion remains an important aspect of patient management in visceral leishmaniasis (VL). However, transfusion triggers considered are poorly understood. This review summarises the transfusion practices adopted in VL efficacy studies using the Infectious Diseases Data Observatory VL clinical trials library. Of the 160 studies (1980–2021) indexed in the IDDO VL library, description of blood transfusion was presented in 16 (10.0%) (n=3459 patients) studies. Transfusion was initiated solely based on haemoglobin (Hb) measurement in nine studies, combining Hb measurement with an additional condition (epistaxis/poor health/clinical instability) in three studies and the criteria was not mentioned in four studies. The Hb threshold range for triggering transfusion was 3–8 g/dL. The number of patients receiving transfusion was explicitly reported in 10 studies (2421 patients enrolled, 217 underwent transfusion). The median proportion of patients who received transfusion in a study was 8.0% (Interquartile range: 4.7% to 47.2%; range: 0–100%; n=10 studies). Of the 217 patients requiring transfusion, 58 occurred before VL treatment initiation, 46 during the treatment/follow-up phase and the time was not mentioned in 113. This review describes the variation in clinical practice and is an important initial step in policy/guideline development, where both the patient's Hb concentration and clinical status must be considered. [ABSTRACT FROM AUTHOR]

Objectives To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods Using serum collected at enrolment, three alarmins (IL-33, thymic stromal lymphopoietin [TSLP] and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enrolment were examined using Cox proportional hazards. Covariates in multivariate models included age, sex, race, smoking status, RA disease activity score and anti-cyclic citrullinated antibody positivity. Results Of 2835 study participants, 115 participants (4.1%) had prevalent RA-ILD at baseline and an additional 146 (5.1%) developed incident ILD. There were no associations between serum alarmin concentrations and prevalent ILD in unadjusted or adjusted logistic regression models. In contrast, there was a significant inverse association between IL-33 concentration and the risk of developing incident RA-ILD in unadjusted (hazard ratio [HR] 0.73 per log-fold increase; 95% CI: 0.57, 0.95; P  = 0.018) and adjusted (HR 0.77; 95% CI: 0.59, 1.00; P  = 0.047) models. No significant associations of TSLP or IL-25 with incident ILD were observed. Conclusion In this study, we observed a significant inverse association between serum IL-33 concentration and the risk of developing incident RA-ILD, but no associations with prevalent ILD. Additional investigation is required to better understand the mechanisms driving this relationship and how serum alarmin IL-33 assessment might contribute to clinical risk stratification in patients with RA. [ABSTRACT FROM AUTHOR]

Objective To evaluate the ACR/EULAR 2022 criteria for ANCA-associated vasculitides (AAV) classification and compare them with the European Medicines Agency (EMA) algorithm and with classification based only on ANCA serology. Methods In the analysis, 374 cases (47% female) were classified according to the EMA algorithm, ANCA serology and ACR/EULAR criteria. The agreement rate was calculated using the kappa (κ) statistic. Results Under EMA, 192 patients were classified as granulomatosis with polyangiitis (GPA), 159 as microscopic polyangiitis (MPA) and 23 as eosinophilic granulomatosis with polyangiitis (EGPA). The ACR/EULAR criteria classified 199 patients as GPA, 136 as MPA and 22 as EGPA. Four patients (1.1%) met criteria of two disease categories, and 13 (3.5%) were unclassifiable. The observed agreement between EMA and ACR/EULAR was 85% for GPA, 75% for MPA and 96% for EGPA. The unweighted κ statistic was 0.66 (95% CI: 0.60, 0.74). Of the 188 PR3-ANCA positive patients, 186 (98.9%) were classified as GPA using ACR/EULAR criteria, and 135 of 161 (83.9%) MPO-ANCA positive patients were classified as MPA. With a classification solely based on ANCA specificity, agreement with ACR/EULAR was 99% for GPA and 88% for MPA. Conclusions EMA and ACR/EULAR classification give similar results. A small proportion of patients cannot be classified or fall into two categories. Some patients exhibiting granuloma, a key feature of GPA, are nevertheless classified as MPA, conflicting with the current view of histopathology of AAV. There is high agreement of ANCA-based classification with that of ACR/EULAR, reflected in the considerable weight granted to ANCA in the new criteria. These crucial elements within the new criteria necessitate a consensus discussion among field experts. [ABSTRACT FROM AUTHOR]

Background A substantial number of patients with multiple myeloma (MM) who have bone destruction are initially admitted into the orthopedic service at the hospital. However, routine laboratory testing usually fails to identify these patients, thus delaying optimal therapy. Therefore, there is a clear medical need for early diagnosis of MM in these patients. Methods Between 2019 and 2021, 42 patients receiving treatment for orthopedic conditions had normal hemoglobin (Hb), total protein (TP), albumin (ALB), creatinine (CREA), and blood calcium (Ca) levels before their surgical procedure(s) but were subsequently pathologically confirmed to have MM, based on their presenting orthopedic symptoms. During the same period, 52 patients with orthopedic conditions were pathologically excluded from the diagnosis of MM and were recruited into our control group. Serum free light chain (sFLC) testing was performed in 94 consecutive patients in the orthopedic service using Siemens N Latex FLC kits. The levels of Hb, TP, ALB, CREA, and Ca were also measured. All 42 patients with MM were divided into group A (n = 25: κ proliferation) and group B (n = 17: λ proliferation) by the pathology department. Results There were no significant differences in levels of Hb, TP, ALB, CREA, and Ca between group A and group B and the control group. However, the sFLC κ/λ ratio of group A and B was also significantly different from that of the control group (P <.001). The results of serum immunofixation electrophoresis (IFE) testing demonstrated negative results in 14 cases (58.3%) in group A and 4 cases (25.0%) in group B. Conclusions Some patients with orthopedic conditions who do not have typical MM laboratory results, such as those with abnormal Hb, TP, ALB, CREA, and Ca levels before their operation(s), actually have MM. MM should be highly suspected in patients with unexplained bone lesions and with an abnormal sFLC κ/λ ratio. Further tissue or bone marrow biopsy is needed in these patients even if serum and urine IFE results are negative and light chain ratio is normal. [ABSTRACT FROM AUTHOR]

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P =.04). Persistent GN-BSI may be a marker of complicated infection. [ABSTRACT FROM AUTHOR]

Background Nontoxigenic Corynebacterium diphtheriae , often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae –positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. Methods We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. Results Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae– positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae –positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. Conclusions Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed. [ABSTRACT FROM AUTHOR]

Background Cell-based quadrivalent-inactivated influenza vaccine has been shown to have higher vaccine effectiveness than traditional egg-based quadrivalent-inactivated influenza vaccine. This is observed despite similar levels of serum hemagglutinin antibodies induced by each vaccine. Methods In this study, we examine peripheral immune activation after egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated, and ribonucleic acid was sequenced from 81 study participants (41 Fluzone, egg based and 40 Flucelvax, cell based) pre- and 7 days postvaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted. Results Cell-based influenza vaccine induced greater interferon-stimulated and innate immune gene activation compared with egg-based influenza vaccine. Participants who seroconverted had increased interferon-signaling activation versus those who did not seroconvert. Conclusions These data suggest that cell-based influenza vaccine stimulates immune activation differently from egg-based influenza vaccine, shedding light on reported differences in vaccine effectiveness. [ABSTRACT FROM AUTHOR]

Background Increasing mortality and morbidity of coronary artery disease (CAD) highlight the emerging need for novel noninvasive markers such as circulating microRNAs (miRNAs). Objective To evaluate the circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326, and their associations with known contributors to CAD, in CAD subgroups. Methods We divided the cohort into 4 groups: non-CAD controls (≤30% stenosis; n = 55), and patients with stable angina pectoris (SAP; n = 48), unstable AP (UAP; n = 46), and myocardial infarction (MI; n = 36). The circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326 were determined using TaqMan Advanced miRNA Assays in serum specimens. Results Circulating miR-126-3p levels were lower in the MI and UAP groups, compared with the non-CAD group, whereas miR-210-3p circulating levels were lower in the MI group than others. The levels of circulating let-7g-5p were shown to be useful for distinguishing UAP from MI, and there were substantial differences in circulating let-7g-5p levels between the UAP and MI groups. Moreover, lipid levels and ratios were lower in individuals with high circulating miR-126-3p and miR-210-3p levels. Conclusions The study results suggest that circulating miR-126-3p, miR-210-3p, and let-7g-5p are differentiated between different clinical presentations of CAD and associated with lipid levels, which are important risk factors and determinants of CAD. [ABSTRACT FROM AUTHOR]

Adult medulloblastoma (MB) is a rare disease affecting 0.6 persons per million adults over 19 years of age. The SHH-activated/TP53-wild type is the most common subtype, accounting for 60% of adult MBs, being characterized by mutations in PTCH1, SMO, or the TERT promoter. Several small studies demonstrate objective but short-lived responses to SMO inhibitors such as vismodegib or sonidegib. Like other oncogene-addicted solid tumors, detection of the corresponding drivers through liquid biopsy could aid in the molecular diagnosis and monitoring of the disease through less invasive procedures. However, most studies have only evaluated cerebrospinal fluid as the ctDNA reservoir, and very limited evidence exists on the role of liquid biopsy in plasma in patients with primary central nervous system tumors, including MB. We present the case of a 26-year-old patient with a recurrent MB, in which next-generation sequencing (FoundationOne CDx) revealed a mutation in PTCH1, allowing the patient to be treated with vismodegib in second line, resulting in a durable benefit lasting for 1 year. Using an in-house digital PCR probe, the PTCH1 mutation could be tracked in ctDNA during treatment with first-line chemotherapy and while on treatment with vismodegib, demonstrating a precise correlation with the radiological and clinical behavior of the disease. [ABSTRACT FROM AUTHOR]

Background The 2023 Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) classification is a new diagnostic tool for infective endocarditis, updating the 2000 modified Duke and the 2015 European Society for Cardiology (ESC) classifications. In comparison, its sensitivity is higher; however, its specificity remains to be evaluated and compared to that of the 2 other classifications in endocarditis suspected patients. Methods We retrospectively collected the characteristics of patients hospitalized in Bichat University's Hospital, Paris, in 2021, who had been evaluated for clinical suspicion of endocarditis, have had at least a transthoracic echocardiography, 2 pairs of blood cultures, 3-month follow-up and in whom endocarditis diagnosis was finally rejected. All patients were classified by 2000 modified Duke, 2015 ESC and 2023 Duke-ISCVID, as though the endocarditis diagnosis had not been rejected. Results In total, 130 patients' charts were analyzed. Mean age was 62 years, 84 (64.6%) were male, 39 (30.0%) had prosthetic cardiac valve or valve repair, 21 (16.2%) cardiac implanted electronic device, and 30 (23.1%) other cardiac conditions. Overall, 5, 2, and 5 patients were falsely classified as definite endocarditis with the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID classifications, respectively. The corresponding specificities were 96.2% (95% confidence interval [CI] [90.8%, 98.6%]), 98.5% (95% CI [93.9%, 99.7%]), and 96.2% (95% CI [90.8%, 98.6%]). The rates of possible endocarditis were of 38%, 35%, and 35% in the 3 classifications, respectively. Conclusions The 2023 Duke-ISCVID classification is highly specific for ruling out the diagnosis of definite infective endocarditis in patients who had been evaluated for IE. [ABSTRACT FROM AUTHOR]

Background The development of chatbot artificial intelligence (AI) has raised major questions about their use in healthcare. We assessed the quality and safety of the management suggested by Chat Generative Pre-training Transformer 4 (ChatGPT-4) in real-life practice for patients with positive blood cultures. Methods Over a 4-week period in a tertiary care hospital, data from consecutive infectious diseases (ID) consultations for a first positive blood culture were prospectively provided to ChatGPT-4. Data were requested to propose a comprehensive management plan (suspected/confirmed diagnosis, workup, antibiotic therapy, source control, follow-up). We compared the management plan suggested by ChatGPT-4 with the plan suggested by ID consultants based on literature and guidelines. Comparisons were performed by 2 ID physicians not involved in patient management. Results Forty-four cases with a first episode of positive blood culture were included. ChatGPT-4 provided detailed and well-written responses in all cases. AI's diagnoses were identical to those of the consultant in 26 (59%) cases. Suggested diagnostic workups were satisfactory (ie, no missing important diagnostic tests) in 35 (80%) cases; empirical antimicrobial therapies were adequate in 28 (64%) cases and harmful in 1 (2%). Source control plans were inadequate in 4 (9%) cases. Definitive antibiotic therapies were optimal in 16 (36%) patients and harmful in 2 (5%). Overall, management plans were considered optimal in only 1 patient, as satisfactory in 17 (39%), and as harmful in 7 (16%). Conclusions The use of ChatGPT-4 without consultant input remains hazardous when seeking expert medical advice in 2023, especially for severe IDs. [ABSTRACT FROM AUTHOR]

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2–10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection. [ABSTRACT FROM AUTHOR]

Objective Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. Methods A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. Results IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s. d. 30.4)] vs 14.4 (5.5), P  < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P  = 0.000), ECV (r = 0.371, P  = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P  = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P  = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P  = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P  < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P  < 0.01), respectively. Conclusion sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM. [ABSTRACT FROM AUTHOR]

The European Society of Cardiology (ESC) 2023 guidelines for the management of infective endocarditis (IE) stress that a multidisciplinary approach is needed to manage patients with IE. In our view, the guidelines do not include the relevant perspectives from modern microbiology. The diagnostic criteria for IE were changed in the ESC 2023 guidelines, and many IE-causing pathogens are either not clearly defined. Moreover, an improved understanding of the relationship between bacterial species and the risk for IE has not been implemented. The guidelines give detailed and, in our view, incorrect instructions about diagnostic testing in blood culture–negative IE without presenting proper evidence. Other important diagnostic aspects, such as the value of repeated blood cultures and incubation time for blood cultures, are not discussed. We believe that a multidisciplinary collaboration that include microbiologists would have improved these guidelines, and we hope for a future harmonization of diagnostic criteria for IE. [ABSTRACT FROM AUTHOR]

Background Dengue cases continue to rise and can overwhelm healthcare systems during outbreaks. In dengue, neutrophil mediators, soluble urokinase plasminogen activator receptor (suPAR) and olfactomedin 4, and mast cell mediators, chymase and tryptase, have not been measured longitudinally across the dengue phases. The utility of these proteins as prognostic biomarkers for severe dengue has also not been assessed in an older adult population. Methods We prospectively enrolled 99 adults with dengue—40 dengue fever, 46 dengue with warning signs and 13 severe dengue, along with 30 controls. Plasma levels of suPAR, olfactomedin 4, chymase and tryptase were measured at the febrile, critical and recovery phases in dengue patients. Results The suPAR levels were significantly elevated in severe dengue compared to the other dengue severities and controls in the febrile (P <.001), critical (P <.001), and recovery (P =.005) phases. In the febrile phase, suPAR was a prognostic biomarker of severe dengue, with an AUROC of 0.82. Using a cutoff derived from Youden's index (5.4 ng/mL) and an estimated prevalence of severe dengue (16.5%) in our healthcare institution, the sensitivity was 71.4% with a specificity of 87.9% in the febrile phase, and the positive and negative predictive values were 54.7% and 95.8%, respectively. Olfactomedin 4 was elevated in dengue patients but not in proportion to disease severity in the febrile phase (P =.04) There were no significant differences in chymase and tryptase levels between dengue patients and controls. Conclusions In adult dengue, suPAR may be a reliable prognostic biomarker for severe dengue in the febrile phase. [ABSTRACT FROM AUTHOR]

Background Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. Methods In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. Results Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P <.001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). Conclusions Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing. Clinical Trials Registration NCT04047719. [ABSTRACT FROM AUTHOR]

Background Nearly half of all pediatric musculoskeletal infections (MSKIs) are culture negative. Plasma microbial cell-free DNA (mcfDNA) sequencing is noninvasive and not prone to the barriers of culture. We evaluated the performance of plasma mcfDNA sequencing in identifying a pathogen, and examined the duration of pathogen detection in children with MSKIs. Methods We conducted a prospective study of children, aged 6 months to 18 years, hospitalized from July 2019 to May 2022 with MSKIs, in whom we obtained serial plasma mcfDNA sequencing samples and compared the results with cultures. Results A pathogen was recovered by culture in 23 of 34 (68%) participants, and by initial mcfDNA sequencing in 25 of 31 (81%) participants. Multiple pathogens were detected in the majority (56%) of positive initial samples. Complete concordance with culture (all organisms accounted for by both methods) was 32%, partial concordance (at least one of the same organism(s) identified by both methods) was 36%, and discordance was 32%. mcfDNA sequencing was more likely to show concordance (complete or partial) if obtained prior to a surgical procedure (82%), compared with after (20%), (RR 4.12 [95% CI 1.25, 22.93], p = .02). There was no difference in concordance based on timing of antibiotics (presample antibiotics 60% vs no antibiotics 75%, RR 0.8 [95% CI 0.40, 1.46], p = .65]). mcfDNA sequencing was positive in 67% of culture-negative infections and detected a pathogen for a longer interval than blood culture (median 2 days [IQR 1, 6 days] vs 1 day [1, 1 day], p < .01). Conclusions Plasma mcfDNA sequencing may be useful in culture-negative pediatric MSKIs if the sample is obtained prior to surgery. However, results must be interpreted in the appropriate clinical context as multiple pathogens are frequently detected supporting the need for diagnostic stewardship. [ABSTRACT FROM AUTHOR]

Objective There are well-described impacts of biological rhythms on human physiology. With the increasing push for routine blood tests for preventative medical care and clinical and physiological research, optimizing effectiveness is paramount. This study aimed to determine whether it is feasible to assess diurnal variations of peripheral lymphocyte prevalence using finger prick blood in a small sample size. Methods Using polychromatic flow cytometry, the prevalence of lymphocytes was assessed using 25 µL fingertip blood samples at 8 AM and 5 PM from 8 participants. Results TH cells and B cells showed significantly higher percentages in the 5 PM samples, whereas NK cells demonstrated a significantly higher morning percentage. T cells, leukocytes, and cytotoxic T cells showed no significant changes. Conclusion The detection of diurnal variations demonstrates that small blood volumes can be used to detect lymphocyte variations. The lower blood volume required provides a new testing method for clinical and research settings. [ABSTRACT FROM AUTHOR]

Objective This study aimed to evaluate the impact of short-term incubation (STI) protocol on clinical outcomes of bloodstream infection (BSI) patients. Methods A total of 1363 positive blood culture records from January 2019 to December 2021 were included. The main clinical outcomes included pathogen identification turnaround time (TAT), antimicrobial susceptibility testing (AST) TAT, and length of total hospital stay. Results The TAT of pathogen identification and AST significantly decreased after implementing the STI protocol (2.2 vs 1.4 days and 3.4 vs 2.5 days, respectively, with P <.001 for both). Moreover, for patients with Gram-negative bacteria (GNB)–infected BSIs, the length of total hospital stay decreased from 31.9 days to 27.1 days, indicating that these patients could be discharged 5 days earlier after implementing the STI protocol (P <.01). Conclusion The protocol led to a significant reduction in TAT and improved clinical outcomes, particularly for GNB organisms. The findings suggest that the STI protocol can improve patient outcomes and hospital resource utilization in the management of BSIs. [ABSTRACT FROM AUTHOR]

Background Based on the association between the hormone receptor and the status of human epidermal growth factor receptor 2 (HER2)-low, we investigated the clinicopathological and prognostic characteristics of the HER2-low status in early-stage triple-negative breast cancer (TNBC). Methods We collected the data of patients with TNBC who received treatment at our hospital and compared the pathological complete response (pCR) rate, overall survival (OS), and breast cancer-specific survival (BCSS) between the HER2-0 and HER2-low subtypes. Results A total of 1445 patients were included in the study, of which 698 patients (48.3%) showed HER2-low status. A similar pCR rate was observed between HER2-0 and HER2-low patients (34.9% vs. 37.4%; P  = .549). T staging, N staging, and HER2 status were associated with BCSS, whereas T staging and N staging were associated with OS. Patients with the HER2-low status showed better BCSS than those with the HER2-0 status (96.6% vs. 93.7%; log-rank P  = .027). In patients with non-pCR, the BCSS of the HER2-low subgroup was better than that of the HER2-0 subgroup (log-rank P  = .047); however, no similar result was observed in patients with pCR. In patients with stage III, the BCSS and OS of the HER2-low subgroup were better than those of the HER2-0 subgroup (BCSS, log-rank P  = .010; OS, log-rank P  = .047). No similar results were observed in patients with stages I and II. Conclusion The HER2-low expression was associated with better BCSS in TNBC, especially in the high-risk groups, suggesting that HER2-low breast cancer is a potential independent biological subtype. [ABSTRACT FROM AUTHOR]

Background Persistent Staphylococcus aureus bacteremia is associated with metastatic infection and adverse outcomes, whereas gram-negative bacteremia is normally transient and shorter course therapy is increasingly advocated for affected patients. Whether the prolonged detection of pathogen DNA in blood by culture-independent systems could have prognostic value and guide management decisions is unknown. Methods We performed a multicenter, prospective, observational study on 102 patients with bloodstream infection (BSI) to compare time to bloodstream clearance according to T2 magnetic resonance and blood cultures over a 4-day follow-up. We also explored the association between duration of detectable pathogens according to T2 magnetic resonance (magnetic resonance–DNAemia [MR-DNAemia]) and clinical outcomes. Results Time to bloodstream clearance according to T2 magnetic resonance was significantly longer than blood culture clearance (HR,.54; 95% CI,.39–.75) and did not differ according to the causative pathogen (P =.5). Each additional day of MR-DNAemia increased the odds of persistent infection (defined as metastatic infection or delayed source control) both in the overall population (OR, 1.98; 95% CI, 1.45–2.70) and in S. aureus (OR, 1.92; 95% CI, 1.12–3.29) and gram-negative bacteremia (OR, 2.21; 95% CI, 1.35–3.60). MR-DNAemia duration was also associated with no improvement in Sequential Organ Failure Assessment score at day 7 from infection onset (OR, 1.76; 95% CI, 1.21–2.56). Conclusions T2 magnetic resonance may help diagnose BSI in patients on antimicrobials with negative blood cultures as well as to identify patients with metastatic infection, source control failure, or adverse short-term outcome. Future studies may inform its usefulness within the setting of antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are important for early tumor immune surveillance. In patients with hematological cancers, NK cells are generally functional deficient and display dysregulations in their receptor repertoires. Acute leukemia is the most common cancer in children, and we here performed a comparative phenotypic profiling of NK cells from B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients to identify aberrant NK cell phenotypes. NK cell phenotypes, maturation, and function were analyzed in matched bone marrow and blood NK cells from BCP-ALL patients at diagnosis, during treatment, and at end of treatment and compared with age-matched pediatric control subjects. Expression of several markers were skewed in patients, but with large interindividual variations. Undertaking a multiparameter approach, we found that high expression levels of NKG2A was the single predominant marker distinguishing NK cells in BCP-ALL patients compared with healthy control subjects. Moreover, naïve CD57−NKG2A NK cells dominated in BCP-ALL patients at diagnosis. Further, we found dysregulated expression of the activating receptor DNAM-1 in resident bone marrow CXCR6+ NK cells. CXCR6+ NK cells lacking DNAM-1 expressed NKG2A and had a tendency for lower degranulation activity. In conclusion, high expression of NKG2A dominates NK cell phenotypes from pediatric BCP-ALL patients, indicating that NKG2A could be targeted in therapies for this patient group. [ABSTRACT FROM AUTHOR]

Purpose This report describes a comprehensive pharmacy-driven rapid bacteremia response program. Summary This novel program positioned the pharmacy department at a large, community health system to receive and respond to critical microbiologic diagnostic testing results, 24/7/365. The program empowered pharmacists to provide centralized, comprehensive care including assessing blood culture Gram stain results, adjusting antibiotic therapy per protocol, ordering repeat blood cultures, analyzing and interpreting rapid molecular diagnostic test results, placing orders for contact isolation, and communicating antibiotic recommendations to the treatment team. In the first year after program implementation, 2,282 blood culture Gram stains and 2,046 rapid diagnostic test results were called in to the pharmacy department. The program reduced the median time to effective therapy in patients who did not already have active antimicrobial orders from over 10 hours to less than 1 hour. Based on the Gram stain results, antibiotics were started per protocol in 34.2% of patients. Based on the rapid molecular diagnostic test results, adjustments were made to antibiotic regimens in 55.7% of cases after discussion with a provider. Of these adjustments, 39.9% were for escalation of antibiotics and 37.7% were for de-escalation of antibiotics. Conclusion By expanding the scope of pharmacy practice, barriers to optimizing clinical care were overcome. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to identify the species of a Halomonas strain isolated from a neonatal blood sample and to understand the potential pathogenicity and characteristic genes of the strain. Methods The genomic DNA of strain 18071143 (identified as Halomonas by matrix-assisted laser desorption-ionization time of flight-mass spectrometry and the 16S ribosomal RNA (rRNA) gene sequence) was sequenced using Nanopore PromethION platforms. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) were calculated using the complete genome sequences of the strain. Comparative genomic analyses were performed on strain 18071143 and 3 strains of Halomonas (Halomonas stevensii S18214, Halomonas hamiltonii KCTC 22154, and Halomonas johnsoniae KCTC 22157) that were associated with human infections and had high genomic similarity to strain 18071143. Results Phylogenetic, ANI, and dDDH similarity analyses based on genome sequence indicated that strain 18071143 belonged to the species H stevensii. Similarities exist between strain 18071143 and the other 3 Halomonas strains in terms of gene structure and protein function. Nonetheless, strain 18071143 has greater potential for DNA replication, recombination, repair, and horizontal transfer. Conclusion Whole-genome sequencing holds great promise for accurate strain identification in clinical microbiology. In addition, the results of this study provide data for understanding Halomonas from the perspective of pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Objectives Five-Factor Model personality traits are associated consistently with cognition. Inflammation has been hypothesized as a biological pathway in this association, but this assumption has yet to be tested. The present study tested inflammatory markers as mediators between personality traits and cognition. Methods Participants were from the Health and Retirement Study (HRS; N = 4,364; 60% women; mean age = 64.48 years, standard deviation = 8.79). Personality traits and demographic factors were assessed in 2010/2012. Data on inflammatory markers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], soluble tumor necrosis factor 1 (sTNFR1), interleukin-10 [IL-10], interleukin-1 receptor antagonist [IL-1Ra], and transforming growth factor [TGF]-β1) were obtained in 2016 from the HRS Venuous Blood Study. Cognition was assessed in 2020 using the modified Telephone Interview for Cognitive Status. Results Higher neuroticism was related to lower cognition at follow-up, whereas higher extraversion, openness, agreeableness, and conscientiousness were associated with better cognition. Higher extraversion and higher conscientiousness were related to lower hsCRP, IL-6, IL-10, IL-1Ra, and sTNFR1, and higher openness was associated with lower IL-10, IL-1Ra, and sTNFR1 and to higher soluble TGF-β1. Lower sTNFR1 partially mediated the associations between conscientiousness, extraversion, and openness and cognition at follow-up, explaining an estimated 4%–12% of these associations. The mediating role of sTNFR1 persisted when physical activity and depressive symptoms were included as additional mediators. Discussion The present study provides new evidence on personality and inflammatory markers. Consistent with the inflammation hypothesis, the sTNFR1 finding supports a potential biological pathway between personality and cognition. [ABSTRACT FROM AUTHOR]

Context The performance of peripheral blood transcriptional markers in evaluating risk of type 2 diabetes (T2D) with normal body mass index (BMI) is unknown. Objective We developed a whole blood–based transcriptional risk score (wb-TRS) for nonobese T2D and assessed its contributions on disease risk and dynamic changes in glucose metabolism. Methods Using a community-based cohort with blood transcriptome data, we developed the wb-TRS in 1105 participants aged ≥40 years who maintained a normal BMI for up to 10 years, and we validated the wb-TRS in an external dataset. Potential biological significance was explored. Results The wb-TRS included 144 gene transcripts. Compared to the lowest tertile, wb-TRS in tertile 3 was associated with 8.91-fold (95% CI, 3.53-22.5) higher risk and each 1-unit increment was associated with 2.63-fold (95% CI, 1.87-3.68) higher risk of nonobese T2D. Furthermore, baseline wb-TRS significantly associated with dynamic changes in average, daytime, nighttime, and 24-hour glucose, HbA1c values, and area under the curve of glucose measured by continuous glucose monitoring over 6 months of intervention. The wb-TRS improved the prediction performance for nonobese T2D, combined with fasting glucose, triglycerides, and demographic and anthropometric parameters. Multi-contrast gene set enrichment (Mitch) analysis implicated oxidative phosphorylation, mTORC1 signaling, and cholesterol metabolism involved in nonobese T2D pathogenesis. Conclusion A whole blood–based nonobese T2D-associated transcriptional risk score was validated to predict dynamic changes in glucose metabolism. These findings suggested several biological pathways involved in the pathogenesis of nonobese T2D. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 47-year-old man with pneumonia, skin lesions, and fever refractory to antibiotics. It mentions the diagnosis of Disseminated Mycobacterium kansasii infection, highlighting the challenges in diagnosis and treatment. Topics discussed include clinical manifestations, diagnostic methods, and treatment regimens for this uncommon infection.

Background Little is known about late-onset sepsis (LOS) evaluations in extremely low gestational age newborns (ELGANs). We describe frequencies of LOS evaluation in ELGANs, infant characteristics, and empiric therapy choices during evaluations. Methods Cohort study of infants 22–28 weeks gestational age (GA) discharged from 243 centers from 2009 to 2018, excluding infants with congenital anomalies, discharged or deceased prior to postnatal day (PND) 2, or admitted after PND 2. A new LOS evaluation was defined as the first blood culture obtained between PND 3 and 90, or one obtained ≥1 day following a negative culture and ≥10 days from prior positive cultures. We determined numbers of evaluations and percentage positive by GA, center, and over time. We described characteristics associated with positive evaluations, infants with LOS, and empiric antimicrobials. We calculated descriptive and comparative statistics using Wilcoxon rank sum, Fisher's exact, or Pearson chi-square tests, as appropriate. Results Of 47,187 included infants, 67% had ≥1 LOS evaluation and 21% of evaluated infants had ≥1 LOS (culture positive) episode; 1.6 evaluations occurred per infant and 10% were positive. The percentage of infants evaluated and positive for LOS was higher at earlier GA. LOS was associated with inotrope support (15% vs. 9%; p  < .001) and invasive mechanical ventilation (66% vs. 51%; p  < .001). Infants with positive cultures were more likely than infants with negative cultures to receive empiric antimicrobials during the LOS evaluation (95% vs. 73%; p  < .001). Conclusions Among ELGANs, earlier GA and postnatal age were associated with LOS evaluation and positive cultures. Most infants undergoing evaluation were started on empiric antimicrobials. [ABSTRACT FROM AUTHOR]

Background We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). Methods We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies. We performed subgroup analysis in EOS episodes caused by Gram-negative and Gram-positive organisms. Results Of the 62,178 infants and 64,559 cultures that met study inclusion criteria, 739 (1%) cultures were positive. The median (25th, 75th percentile) glucose value was 75 mg/dL (50, 106) on the day of or day prior to a positive culture versus 70 mg/dL (50, 95) on the day of or day prior to a negative culture. We found that hypoglycemia was not associated with the occurrence of EOS for all organisms and Gram-positive organisms, whereas there was a small but significant association between the lower AAP glucose cutoff value and EOS due to Gram-negative organisms (logistic regression: risk difference [RD] 0.24% [95% CI, 0.01-0.47]; IPW: RD 0.22% [95% CI, 0.00-0.43]). Conclusions Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia. [ABSTRACT FROM AUTHOR]

Background Incomplete uptake of guidelines can lead to nonstandardized care, increased expenditures, and adverse clinical outcomes. The objective of this study was to evaluate the impact of the 2011 Pediatric Infectious Diseases Society and Infectious Diseases Society of America (PIDS/IDSA) pediatric community-acquired pneumonia (CAP) guideline that emphasized aminopenicillin use and de-emphasized the use of chest radiographs (CXRs) in certain populations. Methods This quasi-experimental study queried a national administrative database of children's hospitals to identify children aged 3 months–18 years with CAP who visited 1 of 28 participating hospitals from 2009 to 2021. PIDS/IDSA pediatric CAP guideline recommendations regarding antibiotic therapy, diagnostic testing, and imaging were evaluated. Segmented regression interrupted time series was used to measure guideline-concordant practices with interruptions for guideline publication and the Coronavirus Disease 2019 (COVID-19) pandemic. Results Of 315 384 children with CAP, 71 804 (22.8%) were hospitalized. Among hospitalized children, there was a decrease in blood culture performance (0.5% per quarter) and increase in aminopenicillin prescribing (1.1% per quarter). Among children discharged from the emergency department (ED), there was an increase in aminopenicillin prescription (0.45% per quarter), whereas the rate of obtaining CXRs declined (0.12% per quarter). However, use of CXRs rebounded during the COVID-19 pandemic (increase of 1.56% per quarter). Hospital length of stay, ED revisit rates, and hospital readmission rates remained stable. Conclusions Guideline publication was associated with an increase of aminopenicillin prescribing. However, rates of diagnostic testing did not materially change, suggesting the need to consider implementation strategies to meaningfully change clinical practice for children with CAP. [ABSTRACT FROM AUTHOR]

Objective A nontargeted metabolomics approach was established to characterize serum metabolic profile in type 3c diabetes mellitus (T3cDM) secondary to chronic pancreatitis and compare with T2DM. Methods Forty patients were recruited for metabolite analysis based on liquid chromatography-mass spectrometry. Cluster heatmap and KEGG metabolic pathway enrichment analysis were used to analyze the specific and differential metabolites. The receiver operating characteristics (ROCs) were generated and correlation analysis with clinical data was conducted. Results Metabolites including sphingosine, lipids, carnitine, bile acid, and hippuric acid were found to be different between T2DM and T3cDM, mainly enriched in bile acid biosynthesis, fatty acid biosynthesis, and sphingolipid metabolic pathways. The ROCs were generated with an area under the curve of 0.907 (95% confidence interval, 0.726–1) for the model with 15 metabolites. Conclusion T3cDM is characterized by increased sphingosine, carnitine, bile acid, and most lipids, providing novel biomarkers for clinical diagnosis and a future direction in research on pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

In the past decade, the prevalence of multidrug-resistant gram-negative (MDR-GN) bacterial infections has increased significantly, leading to higher rates of morbidity and mortality. Treating these infections poses numerous challenges, particularly when selecting appropriate empiric therapy for critically ill patients for whom the margin for error is low. Fortunately, the availability of new therapies has improved the treatment landscape, offering safer and more effective options. However, there remains a need to establish and implement optimal clinical and therapeutic approaches for managing these infections. Here, we review strategies for identifying patients at risk for MDR-GN infections, propose a framework for the choice of empiric and definitive treatment, and explore effective multidisciplinary approaches to managing patients in the hospital while ensuring a safe transition to outpatient settings. [ABSTRACT FROM AUTHOR]

Background Invasive aspergillosis (IA) in immunocompromised hosts carries high morbidity and mortality. Diagnosis is often delayed because definitive diagnosis requires invasive specimen collection, while noninvasive testing with galactomannan is moderately accurate. Plasma cell-free DNA polymerase chain reaction (cfDNA PCR) represents a novel testing modality for the noninvasive diagnosis of invasive fungal disease (IFD). We directly compared the performance of Aspergillus plasma cfDNA PCR with serum galactomannan for the diagnosis of IA during routine clinical practice. Methods We conducted a retrospective study of all patients with suspected IFD who had Aspergillus plasma cfDNA PCR testing at Stanford Health Care from 1 September 2020 to 30 October 2022. Patients were categorized into proven, probable, possible, and no IA based on the EORTC/MSG definitions. Primary outcomes included the clinical sensitivity and specificity for Aspergillus plasma cfDNA PCR and galactomannan. Results Overall, 238 unique patients with Aspergillus plasma cfDNA PCR test results, including 63 positives and 175 nonconsecutive negatives, were included in this study. The majority were immunosuppressed (89.9%) with 22.3% 30-day all-cause mortality. The overall sensitivity and specificity of Aspergillus plasma cfDNA PCR were 86.0% (37 of 43; 95% confidence interval [CI], 72.7–95.7) and 93.1% (121 of 130; 95% CI, 87.4–96.3), respectively. The sensitivity and specificity of serum galactomannan in hematologic malignancies/stem cell transplants were 67.9% (19 of 28; 95% CI, 49.3–82.1) and 89.8% (53 of 59; 95% CI, 79.5–95.3), respectively. The sensitivity of cfDNA PCR was 93.0% (40 of 43; 95% CI, 80.9–98.5) in patients with a new diagnosis of IA. Conclusions Aspergillus plasma cfDNA PCR represents a more sensitive alternative to serum galactomannan for noninvasive diagnosis of IA. [ABSTRACT FROM AUTHOR]

Background Despite being the leading cause of mortality from bloodstream infections worldwide, little is known about regional variation in treatment practices for Staphylococcus aureus bacteremia (SAB). The aim of this study was to identify global variation in management, diagnostics, and definitions of SAB. Methods During a 20-day period in 2022, physicians throughout the world were surveyed on SAB treatment practices. The survey was distributed through listservs, e-mails, and social media. Results In total, 2031 physicians from 71 different countries on 6 continents (North America [701, 35%], Europe [573, 28%], Asia [409, 20%], Oceania [182, 9%], South America [124, 6%], and Africa [42, 2%]) completed the survey. Management-based responses differed significantly by continent for preferred treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteremia, use of adjunctive rifampin for prosthetic material infection, and use of oral antibiotics (P <.01 for all comparisons). The 18F-FDG PET/CT scans were most commonly used in Europe (94%) and least frequently used in Africa (13%) and North America (51%; P <.01). Although most respondents defined persistent SAB as 3 – 4 days of positive blood cultures, responses ranged from 2 days in 31% of European respondents to 7 days in 38% of Asian respondents (P <.01). Conclusions Large practice variations for SAB exist throughout the world, reflecting the paucity of high-quality data and the absence of an international standard of care for the management of SAB. [ABSTRACT FROM AUTHOR]

Objective miRNAs are small non-coding RNAs that control gene expression. Specific intra- and extracellular miRNA signatures have been identified in various diseases. Whether certain miRNA signatures are associated with psoriasis (PsO) and PsA is currently unknown. We aimed to search for circulating miRNA signatures associated with PsO and PsA patients. Methods Expression of miRNAs was analysed by reverse transcription quantitative real-time PCR (RT-qPCR) in the serum of PsA, PsO patients and healthy controls. Demographic and disease-specific characteristics and imaging data from hand MRI were recorded. In the discovery phase, 192 miRNA assays were analysed in 48 samples (PsA, PsO, controls: each N  = 16). For validation, 17 selected miRNAs were measured in the total population. Results A total of 141 patients and controls were analysed (51 PsA, 40 PsO, 50 controls). In the discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared with controls, with 33 miRNAs being changed in both (adj. P  < 0.05). The 17 top candidates from discovery were assessed in the validation phase, 9 of them discriminated PsA and PsO from controls [area under the curve (AUC) ≥0.70, all P  < 0.05]. Four miRNAs (miR-19b-3p, miR-21-5p, miR-92a-3p and let-7b-5p) were significantly differently regulated between PsO and PsA. A combination of these miRNAs increased the AUC to 0.92 in multivariate regression model to discriminate PsO and PsA. Conclusion miRNA signatures in PsA and PsO patients differ from controls. Nine miRNAs were differentially regulated in PsA and PsO patients, five of them previously reported to be involved in bone and cartilage metabolism, indicating an intimate association of psoriatic inflammation and bone/cartilage changes. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 63-year-old male with a history of mental illness and bilateral intraocular lens implantation, who presented with severe left ocular pain, swelling, and a foul-smelling purulent discharge containing live maggots in the orbital cavity. It mentions the patient was admitted to the hospital, received antibiotic therapy, and underwent various tests to determine the cause of the condition.

The article discusses the challenges in diagnosing pneumonia in immunocompromised patients and the potential of plasma cell-free DNA metagenomic sequencing (mcfDNA) to enhance diagnostic capabilities. Topics include the limitations of traditional microbiologic methods, the use of mcfDNA sequencing for detecting pneumonia pathogens, and the results and implications of the PICKUP study, which evaluated the diagnostic value of mcfDNA sequencing in patients with hematologic cancer.

Serum κ and λ free light chains can be markedly elevated in monoclonal gammopathies; consequently, serum free light chain (sFLC) immunoassays are susceptible to inaccuracies caused by antigen excess. As a result, diagnostics manufacturers have attempted to automate antigen excess detection. A 75-year-old African-American woman had laboratory findings consistent with severe anemia, acute kidney injury, and moderate hypercalcemia. Serum and urine protein electrophoresis and sFLC testing were ordered. The sFLC results initially showed mildly elevated free λ light chains and normal free κ. The pathologist noted that sFLC results were discrepant with the bone marrow biopsy, electrophoresis, and immunofixation results. After manual dilution of the serum, repeat sFLC testing revealed significantly higher λ sFLC results. Antigen excess causing falsely low sFLC quantitation may not be detected by immunoassay instruments as intended. Correlation with clinical history, serum and urine protein electrophoresis results, and other laboratory findings is essential when interpreting sFLC results. [ABSTRACT FROM AUTHOR]

Background Lyme disease is the most prevalent vector-borne disease in the US, yet its host factors are poorly understood and diagnostic tests are limited. We evaluated patients in a large health system to uncover cholesterol's role in the susceptibility, severity, and machine learning–based diagnosis of Lyme disease. Methods A longitudinal health system cohort comprised 1 019 175 individuals with electronic health record data and 50 329 with linked genetic data. Associations of blood cholesterol level, cholesterol genetic scores comprising common genetic variants, and burden of rare loss-of-function (LoF) variants in cholesterol metabolism genes with Lyme disease were investigated. A portable machine learning model was constructed and tested to predict Lyme disease using routine lipid and clinical measurements. Results There were 3832 cases of Lyme disease. Increasing cholesterol was associated with greater risk of Lyme disease and hypercholesterolemia was more prevalent in Lyme disease cases than in controls. Cholesterol genetic scores and rare LoF variants in CD36 and LDLR were associated with Lyme disease risk. Serological profiling of cases revealed parallel trajectories of rising cholesterol and immunoglobulin levels over the disease course, including marked increases in individuals with LoF variants and high cholesterol genetic scores. The machine learning model predicted Lyme disease solely using routine lipid panel, blood count, and metabolic measurements. Conclusions These results demonstrate the value of large-scale genetic and clinical data to reveal host factors underlying infectious disease biology, risk, and prognosis and the potential for their clinical translation to machine learning diagnostics that do not need specialized assays. [ABSTRACT FROM AUTHOR]

Background Endothelial dysfunction (ED) has a well-known role in promoting vascular inflammation in Behçet disease (BD). α-klotho is involved in regulation of endothelial function, and its reduction has been reported to be associated with ED.  Objective To assess serum α-klotho in patients with BD, compared with healthy control individuals. Methods In a cross-sectional study, 55 patients with BD and 30 age- and sex-matched healthy controls were enrolled, and their serum levels of α-klotho were measured. Results Common clinical symptoms in patients with BD were oral aphthous ulcers, uveitis, and genital ulcers. Median (IQR) serum α-klotho levels in the BD and control groups were 0.30 (0.20–0.70) and 1.00 (0.70–2.52) ng/mL, respectively. The difference was statistically significant (P  = .005). No significant correlation was observed between serum α-klotho and age (r  = 0.194; P  = .14). Serum α-klotho levels in patients with uveitis were significantly lower. Conclusion α-klotho may have a role in the pathogenesis of ED and is a potential biomarker for uveitis in BD. [ABSTRACT FROM AUTHOR]

Background Our aim in this study was to evaluate the clinical and prognostic impact of communicating microbiological information in real time for adult patients with bloodstream infections (BSIs). Methods We retrospectively reviewed 6225 clinical episodes of bacteremia in a teaching hospital from January 2013 to December 2019. Bacteremia-associated mortality was compared when blood culture results were relayed to the infectious diseases specialist (IDS) in real time and periods when results were relayed the following morning. The impact of information availability using mortality at 30 days was used as the main outcome of the study. Results The initial analysis (all microorganisms included) did not show an association of mortality and information delay to the IDS (odds ratio [OR], 1.18; 95% confidence interval [CI],.99–1.42). However, information delay of BSIs caused by fast-growing microorganisms such as Enterobacterales was associated with a significant increase in the odds of death at 30 days both in the univariate (OR, 1.76; 95% CI, 1.30–2.38) and multivariate analysis (OR, 2.22; 95% CI, 1.50–3.30). Similar results were found with mortality at 14 days and 7 days in the univariate (OR, 1.54; 95% CI, 1.08–2.20 and OR, 1.56; 95% CI, 1.03–2.37, respectively) and the multivariate analysis (OR, 2.05; 95% CI, 1.27–3.32 and OR, 1.92; 95% CI, 1.09–3.40, respectively). Conclusions Information delivered in real time has prognostic relevance and is likely to improve survival of patients with documented BSIs. Future studies should address the prognostic impact of adequate resource allocation (microbiologist/IDS with 24/7 coverage) in BSIs. [ABSTRACT FROM AUTHOR]

Data on the performance of blood-based nucleocapsid antigen tests for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and infectious viral shedding are limited. To address this knowledge gap, we conducted a systematic review to assess the performance of blood-based nucleocapsid (N) antigen tests in diagnosing SARS-CoV-2 infection and identifying infectiousness. This review was registered on PROSPERO (registration no. CRD42022339635). We comprehensively searched PubMed, Embase, Web of Science, and the Coronavirus Research Database for relevant studies published through 27 February 2023. Each study's risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Our findings indicate that the performance of the N-antigen test is influenced by factors such as assay type, sampling timing, and illness severity. Sensitive assays provide suitable methods for viable screening and laboratory diagnostic tests in different clinical and research settings during the early phase of illness. [ABSTRACT FROM AUTHOR]

Background Differential time to positivity (DTP), defined as pathogen growth at least 2 hours earlier from catheter versus paired peripheral blood cultures, is sometimes used to diagnose central line–associated bloodstream infections (CLABSIs). Previous studies assessing DTP, however, have been small, provided conflicting results, and did not assess heterogeneity across important subgroups. Methods We systematically reviewed the diagnostic characteristics of DTP for CLABSI using MEDLINE, Embase, WoS, CINAHL, LILACS, AMED, and the Cochrane database. Studies were included if they reported sensitivities, specificities, predictive values, likelihood ratios, or 2 × 2 tables of DTP for diagnosing CLABSI. Extracted data were analyzed by using forest plots, bivariate model meta-analysis, and QUADAS-2 quality assessment. Results We identified 274 records, of which 23 met the criteria for meta-analysis. Among 2526 suspected CLABSIs, DTP demonstrated a summary sensitivity of 81.3% (95% confidence interval [CI]: 72.8%–87.7%), specificity of 91.8% (95% CI: 84.5%–95.8%), positive likelihood ratio of 9.89 (95% CI: 5.14–19.00), and negative likelihood ratio of 0.20 (95% CI:.14–.30). Covariate analysis based on catheter duration, study design, and patient immune status demonstrated no significant differences. However, DTP performed worse for Staphylococcus aureus (low sensitivity but high specificity) and Candida (high sensitivity but low specificity) compared to other organisms. Conclusions DTP performs well in ruling CLABSIs in or out. Obtaining paired catheter and peripheral blood cultures for DTP when the infectious source is unclear may prevent unnecessary line removal and diagnostic tests. However, this must be balanced against higher contamination rates from catheter cultures. [ABSTRACT FROM AUTHOR]