Hyungdon Lee

Background: Extended-spectrum β-lactamase (ESBL)–producing Enterobacterales are an increasing cause of complicated urinary tract infections (UTIs). Reliance on carbapenems to treat these infections accelerates resistance, underscoring the urgent need for effective oral transition options to preserve last-line agents and lessen healthcare burden. Methods: We conducted a multicenter, open-label, randomized, noninferiority trial at four tertiary hospitals in South Korea (November 2022–June 2025). Adults hospitalized with complicated UTIs due to ESBL-producing Enterobacterales who improved after 3–7 days of intravenous antibiotics were randomized (1:1) to either continue intravenous carbapenem or β-lactam/β-lactamase inhibitor therapy or switch to oral fosfomycin trometamol (3 g once daily). The primary outcome was clinical cure, defined as resolution of urinary tract infection–related symptoms and signs within 4 days after completion of treatment. Secondary outcomes included microbiological cure, readmission, adverse events, and 30-day recurrence. Results: Of the 344 screened patients, 299 were randomized (152 oral fosfomycin; 147 intravenous therapy). Clinical cure occurred in 92.8% of the oral fosfomycin group and 95.2% of the intravenous group (risk difference, −2.47%; 95% CI −7.84 to 2.89), confirming noninferiority. Microbiological cure was similarly high in both groups: urine (98.0% vs 96.6%) and blood (97.3% vs 97.5%). Safety profiles and 30-day outcomes were also comparable. Conclusions: Oral fosfomycin was noninferior to continued intravenous therapy when used as oral transition therapy for complicated UTIs caused by ESBL-producing Enterobacterales. These findings provide evidence to support oral fosfomycin transition as a carbapenem-sparing antibiotic stewardship strategy for patients with complicated UTIs caused by ESBL-producing Enterobacterales. Clinical Trials Registration: KCT0007669.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness caused by the SFTS virus (SFTSV). We conducted this study to propose a scientific evidence-based treatment that can improve prognosis through changes in viral load and inflammatory cytokines according to the specific treatment of SFTS patients. This prospective and observational study was conducted at 14 tertiary referral hospitals, which are located in SFTS endemic areas in Korea, from 1 May 2018 to 31 October 2020. Patients of any age were eligible for inclusion if they were polymerase chain reaction positive against SFTSV, or showed a four-fold or higher increase in IgG antibody titers between two serum samples collected during the acute and convalescent phases. On the other hand, patients with other tick-borne infections were excluded. In total, 79 patients were included in the study. The viral load of the group treated with steroids was 3.39, 3.21, and 1.36 log₁₀ RNA copies/reaction at each week since the onset of symptoms, and the viral load in patients treated with plasma exchange was 4.47, 2.60, and 2.00 log₁₀ RNA copies/reaction at each week after symptom onset. The inflammatory cytokines were not reduced effectively by any specific treatment except IVIG for the entire treatment period. Secondary infections according to pathogens revealed four bacterial (26.7%) and one fungal (6.7%) infection in the steroid group. The viral load of SFTSV and inflammatory cytokines cannot be decreased by steroid and plasma exchange treatments. Secondary bacterial infections can occur when steroids are administered for the treatment of SFTS. Therefore, caution should be exercised when choosing treatment strategies for SFTS.

Airway inflammatory diseases, such as asthma, are a global public health concern owing to their chronic inflammatory effects on the respiratory mucosa. Molecular hydrogen (H₂) has recently been recognized for its antioxidant and anti-inflammatory properties. In this study, we examined the therapeutic potential of H₂ in airway inflammation using an ovalbumin (OVA)-induced BALB/c mouse model of allergic asthma. Female BALB/c mice were sensitized and challenged with OVA to induce airway inflammation, and 30 mice were randomly divided into five groups: NT (non-treatment), HTC (3% H₂ treatment only), NC (negative control, OVA only), PC (positive control, OVA + intranasal 1 mg/mL salbutamol 50 μL), and HT (H₂ treatment, OVA + inhaled 3% H₂). Various inflammatory and oxidative stress (OS)-induced markers such as white blood cells (WBCs) and their differential counts, lung histology, cytokine levels such as interleukin (IL)-4, (IL)-5, (IL)-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), (IL)-10, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT), and total immunoglobulin E (IgE) levels were investigated. Our results showed that inhaled H₂ significantly reduced inflammatory cell infiltration, OS markers, and pro-inflammatory cytokine expression while upregulating antioxidant enzyme activity. Furthermore, H₂ also significantly decreased serum IgE levels, a marker of allergic inflammation. Collectively, our findings suggest that H₂ inhalation is a promising treatment option for airway inflammation, offering a novel approach with potential clinical applications.

Cervical and prostate cancer account for 7.1 and 7.3 deaths per 100,000 people globally in 2022. These rates increased significantly to 17.6 and 17.3 in Africa, respectively, making them the second and third leading cause of cancer deaths in Africa, only surpassed by breast cancer. The human papillomavirus is the prime risk factor for cervical cancer infection. On the other hand, prostate cancer risks include ageing, genetics, race, geography, and family history. However, these factors alone cannot account for the high mortality rate in Africa, which is more than twice the global mortality rate for the two cancers. We searched PubMed, Embase, Scopus, and Web of Science to select relevant articles using keywords related to microorganisms involved in cervical and prostate cancer and the impact of poor healthcare systems on the mortality rates of these two cancers in Africa by carrying out a detailed synopsis of the studies on microbial agents involved and the contributory factors to the deteriorating healthcare system in Africa. It became apparent that the developed countries come first in terms of the prevalence of cervical and prostate cancer. However, more people per capita in Africa die from these cancers as compared to other continents. Also, microbial infections (bacterial or viral), especially sexually transmitted infections, cause inflammation, which triggers the pathogenesis and progression of these cancers among the African population; this has been linked to the region’s deficient health infrastructure, making it difficult for people with microbial infections to access healthcare and hence making infection control and prevention challenging. Taken together, untreated microbial infections, primarily sexually transmitted infections due to the deficient healthcare systems in Africa, are responsible for the high mortality rate of cervical and prostate cancer.

CfDNA is known to be a beneficial biomarker for the diagnosis, treatment response, and prognosis of sepsis. Previous cell line studies have shown that cfDNA in septic mice triggers inflammatory responses and tissue damage, and the mechanism occurs by binding to toll-like receptors (TLRs). Meanwhile, reactive oxidative species (ROS) and nitric oxide (NO) are increased in sepsis, which is known to be associated with organ failure and poor prognosis of sepsis through immunoredox imbalance. This study investigates the occurrence and mechanisms of inflammatory responses when cfDNA from septic mice is administered to macrophages (RAW 264.7 cells) and normal ICR mice aged 7-9 weeks. In addition, cfDNA-activated genes and their pathways are investigated and studied. Tumor necrosis factor-alpha (TNF-α) measured 24 hours after administration of 100, 200, and 400 ng/mL of sepsis-derived cfDNA to healthy mice was significantly higher in the 400 ng/mL group than in the control group. Furthermore, in macrophage cell line experiments, total ROS, NO, and catalase concentrations measured at 24 hours after cfDNA administration were significantly increased compared to the control group. In the meantime, cell viability studies revealed that the viability of the group treated with cfDNA from septic mice was much lower than that of the control group treated with normal human cfDNA. Cytokine levels such as granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-σ), interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF) were significantly higher in the 5 ng/mL group when compared to the 1 ng/mL group, but levels of IL-1β and IL-6 were not significantly higher. Finally, we measured the expression levels of several oxidative stress genes and receptor (TLR) genes and found that 46 cytokines & chemokines genes, namely II23a, Cxc10, XcI1, Csf1, Tnfsf10, Tnf, II10, Tgfb2, Ltb, II15, CcI22, Cd70, Cc15, Lta, CxcI11, Cntf, Ctf1, Bmp6, II11, II22, II24, II27, CxcI12, Ccl7, Tnfsf11, Gapdh, Hprt, Ppia, RpI13a, Tbp, Spp1, Cd40lg, Cxcl3, Cxcl1, lfng, Thpo, Ppbp, II5, II13, Fasl, Ccl11, Bmp4, Ccl4, Cxc19, Adipoq and Tnfrs11b and 18 oxidative stress genes, namely Sod3, Gpx1, Ucp2, Krt1, Cygp, II19, Rag2, Epx, Hspa1a, Psmb5, Prdx2, Txn1, Ngb, Nox4, Ercc2, Ncf2, Noxo1, and Ptgs1 were expressed at various levels, and 13 receptor genes, namely Sod3, Gpx1, Cd80, NfkbiL1, Tlr3, II2, Eif2ak2, II6ra, Hmgb1, Chuk, Tirap, Tradd, and Mapk8ip3, were also expressed at various levels. cfDNA from septic mice and healthy humans exhibit different immunoredox responses through immunoredox-related gene pathways.

Background: The delta neutrophil index (DNI), a prognostic and diagnostic marker for sepsis, is based on the leukocyte count. Platelet activation, similar to leukocyte activation, plays a crucial role in host defense against pathogens and may serve as a predictor of sepsis outcome. However, the combined evaluation of mean platelet component (MPC) and DNI has rarely been used to assess sepsis. Methods: To assess the prognostic and diagnostic validity of the simultaneous evaluation of DNI and MPC in cases of human febrile sepsis, we conducted measurements of cellular indices, including DNI and MPC, as well as molecular biomarkers, including procalcitonin (PCT) and C-reactive protein (CRP). This study was carried out in patients admitted to the emergency department with suspected sepsis. Results: Using a cutoff value of 2.65%, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the DNI in sepsis were found to be 69%, 73.9%, 77.9%, and 64.1%, respectively. Furthermore, significant differences in DNI and MPC levels were observed between the sepsis and non-sepsis groups (6.7 ± 7.8% versus 2.1 ± 2.2% (p = 0.000) and 26.0 ± 1.9 g/dL versus 26.8 ± 1.4 g/dL (p = 0.002), respectively). Notably, there was a negative correlation between DNI and MPC, with the strength of the correlation varying based on the cause of sepsis. By setting the cutoff value of the DNI to 6.2%, its sensitivity, specificity, and NPV improved to 100%, 80.3%, and 100%, respectively, although the PPV remained at 10.6%. Conclusions: In our study, the DNI demonstrates superior effectiveness compared with other molecular biomarkers, such as CRP and procalcitonin, in distinguishing septic febrile patients from non-septic febrile patients. Additionally, a negative correlation exists between MPC and DNI, making MPC a valuable marker for differentiating the etiology of sepsis. These findings hold significant clinical implications, as DNI/MPC evaluation is a cost-effective and readily applicable approach in various impending sepsis scenarios. Notably, this study represents the first examination of the prognostic and diagnostic validity of employing the simultaneous evaluation of DNI and MPC in human cases of febrile sepsis.

Background The Delta Neutrophil Index (DNI), a prodiagnostic marker for sepsis, utilizes leukocyte count. Platelet activation, similar to leukocytes, plays a crucial role in host defence against pathogens and may serve as a predictor of sepsis outcome. However, the combined evaluation of Mean Platelet Component (MPC) and DNI in assessing sepsis has been rarely used. Methods To assess the prodiagnostic validity of simultaneous utilization of DNI and MPC in cases of human febrile sepsis, we conducted measurements of cellular indices, including DNI and MPC, as well as molecular biomarkers such as procalcitonin (PCT) and C-reactive protein (CRP). This study was carried out on patients admitted to the emergency department with suspected sepsis. Results Using a cutoff value of 2.65%, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DNI in sepsis were found to be 69%, 73.9%, 77.9%, and 64.1%, respectively. Furthermore, significant differences in DNI and MPC levels were observed between the sepsis and non-sepsis groups (6.7±7.8% versus 2.1±2.2%, P=0.000 and 26.0±1.9 g/dl versus 26.8±1.4 g/dl, P=0.002), respectively. Notably, there was a negative correlation between DNI and MPC, with the strength of the correlation varying based on the cause of sepsis. By setting the cutoff value for DNI at 6.2%, the sensitivity, specificity, and NPV improved to 100%, 80.3%, and 100%, respectively, although the PPV remained at 10.6%. Importantly, the DNI≥6.2 group exhibited a higher incidence of death (10.9%, 5/46) and multiorgan failure (19.6%, 9/46) compared to the DNI<6.2 group (0.0%, 0/46 and 0.0%, 0/167, respectively) (P=0.000 and P=0.000, respectively). Conclusions In our study, DNI demonstrates superior effectiveness compared to other molecular biomarkers such as CRP and procalcitonin in distinguishing febrile septic patients from febrile nonseptic patients and predicting prognosis. Additionally, there exists a negative correlation between MPC and DNI, making MPC a valuable marker for differentiating the etiology of sepsis. These findings hold significant clinical implications as DNI/MPC is a cost-effective and readily applicable approach in various impending sepsis scenarios. Notably, this study represents the first examination of the prodiagnostic validity of simultaneously employing DNI and MPC in human cases of febrile sepsis.

Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are disorders with similar clinical features; therefore, differentiating between them is difficult. We retrospectively collected data from 183 SFTS and 178 scrub typhus patients and validated an existing scoring system to develop a more sensitive, specific, and objective scoring system. We first applied the scoring systems proposed by Kim et al. to differentiate SFTS from scrub typhus. Multivariable logistic regression revealed that altered mental status, leukopenia, prolonged activated partial thromboplastin time (aPTT), and normal C-reactive protein (CRP) level (≤1.0 mg/dL) were significantly associated with SFTS. We changed the normal CRP level from ≤1.0 mg/dL to ≤3.0 mg/dL and replaced altered mental status with the creatine kinase (CK) level. The modified scoring system showed 97% sensitivity and 96% specificity for SFTS (area under the curve (AUC): 0.983) and a higher accuracy than the original scoring system (p = 0.0308). This study’s scoring system had 97% sensitivity and 98% specificity for SFTS (AUC: 0.992) and a higher accuracy than Kim et al.’s original scoring system (p = 0.0308). Our scoring system that incorporated leukopenia, prolonged aPTT, normal CRP level (≤3.0 mg/dL), and elevated CK level (>1000 IU/L) easily differentiated SFTS from scrub typhus in an endemic area.