Effectiveness of quadrivalent meningococcal conjugate vaccine against meningococcal carriage and genotype character changes: A secondary analysis of prospective cohort study in Korean military trainees.

OBJECTIVE: We evaluated the changes and molecular epidemiology of meningococcal carriage in military recruits after quadrivalent meningococcal conjugate vaccines (MenACWY) vaccination. METHODS: Oropharyngeal swabs were obtained at the beginning and end of the 5-week training. Carriage rates before and after vaccination were compared to estimate vaccine effectiveness (VE). Cultured isolates were characterized by multi-locus sequence typing (MLST). RESULTS: Of 866 vaccinated participants, the overall carriage rate was 10.6% prior to MenACWY vaccination and it tended to decrease to 9.5% after 5 weeks of vaccination (P =0.424). Carriage rate of serogroup ACWY decreased significantly after vaccination (VEACWY = 72.6%, 95%CI: 36.3 - 88.2%), and serogroup C was particularly reduced (VEC = 83.0%, 95%CI: 50.6 - 94.1%), whereas nongroupable isolates increased significantly after vaccination (VENG = -76.1%, 95%CI: -176.2 - -13.1%). Among 99 carriage isolates with complete MLST profiles, 45 different sequence types with nine clonal complexes (CCs) were identified, and 35.3% of the carriage isolates belonged to hypervirulent strains such as CC-32, CC-41/44, and CC-269. CONCLUSIONS: MenACWY vaccination in military recruits led to reduced carriage rates of serogroups C, W, and Y within a short 5-week period. However, serogroup B isolates belonging to the hypervirulent lineage remained after the implementation of MenACWY vaccination.

Impact of prolonged carbapenem use-focused antimicrobial stewardship on antimicrobial consumption and factors affecting acceptance of recommendations: a quasi-experimental study.

This study aimed to assess the impact of a prolonged carbapenem use-focused antimicrobial stewardship program (ASP) on antimicrobial consumption and clinical outcomes and to analyze factors affecting adherence to interventions. Patients prescribed carbapenems for ≥ 2 weeks received intervention. Interrupted time-series analysis was performed to compare antimicrobial consumption before and after intervention. Factors associated with non-adherence to intervention were investigated. Of 273 patients who were eligible for intervention, discontinuation or de-escalation was recommended in 256 (94.1%) and intervention was accepted in 136 (53.1%) patients. Before intervention, carbapenem consumption significantly increased to 1.14 days of therapy (DOT)/1000 patient days (PD)/month (P = 0.018). However, it significantly declined by - 2.01 DOT/1000 PD/month without an increase in other antibiotic consumption (P < 0.001). Factors affecting non-adherence to intervention were younger age (odds ratio [OR] = 0.98; 95% confidence interval [CI] 0.96-1.00), solid organ malignancy (OR = 2.53, 95% CI 1.16-5.50), and pneumonia (OR = 2.59, 95% CI 1.08-6.17). However, ASP intervention was not associated with clinical outcomes such as length of hospital stay or mortality. Prolonged carbapenem prescription-focused ASP significantly reduced carbapenem consumption without adverse outcomes. Non-adherence to interventions was attributed more to prescriber-related factors, such as attitude, than patient-related factors including clinical severity.

Clinical characteristics of nontuberculous mycobacterial disease in people living with HIV/AIDS in South Korea: A multi-center, retrospective study.

With the introduction of combination antiretroviral therapy (cART), the prevalence of human immunodeficiency virus (HIV)-associated nontuberculous mycobacteria (NTM) disease has declined. However, NTM diseases still occur in people living with HIV/acquired immunodeficiency syndrome (AIDS) (PLWHA). We analysed the clinical and microbiological features of NTM diseases in PLWHA in South Korea. PLWHA who were diagnosed with NTM diseases between January 2000 and March 2021 were retrospectively enrolled from five different hospitals in South Korea. Data on baseline demographics, HIV status, CD4+ T cell counts, viral load, past and current cART regimens, isolated NTM species, results of antimicrobial susceptibility tests, treatment regimens, and outcomes were collected by reviewing medical records. A total of 34 cases of NTM in PLWHA were included. Pulmonary and extrapulmonary NTM diseases accounted for 58.8% (n = 20) and 41.2% (n = 14), respectively. The lymph node was the most common site of extrapulmonary NTM disease (64.3%). The age at the time of NTM disease diagnosis was younger in the extrapulmonary NTM group than in the pulmonary NTM group (37.0 vs. 49.0 years). Mean CD4+ T cell counts at the time of NTM disease diagnosis was 186.6 cells/µL (range: 1-1394). Nine patients (26.5%) had fully suppressed viral loads at the time of NTM disease diagnosis. Mycobacterium avium complex (MAC) was the most common species found, followed by M. intracellulare and M. kansasii. MAC isolates were all susceptible to clarithromycin, but the rates of non-susceptibility to moxifloxacin, linezolid, ethambutol, and rifampin were 75%, 37.5%, 12.5%, and 12.5%, respectively. The average duration of treatment was 17 months and the mortality rate was 8.8%. NTM diseases may occur in PLWHA, even with completely suppressed viral loads. The identified clinical features of NTM diseases are essential for its clinical management in South Korea.

Impact of Area Under the Concentration-Time Curve-Guided Monitoring on Vancomycin Nephrotoxicity and Treatment Outcomes in Methicillin-Resistant Staphylococcus Aureus Bacteremia in Korean Patients.

Background: Current guidelines for the therapeutic monitoring of vancomycin recommend dosing based on the area under the concentration-time curve (AUC) to achieve clinical efficacy while reducing nephrotoxicity. Although a wide range of nephrotoxicity thresholds have been reported, few studies have documented clinical outcomes based on AUC-guided vancomycin dosing in Korea. Objective: The aim of the study was to evaluate whether a relationship exists between AUC and treatment outcomes in vancomycin treated patients in methicillin-resistant Staphylococcus aureus bacteremia. Furthermore, this study tries to estimate AUC threshold for treatment failure and nephrotoxicity. Methods: The records of adult patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin for ≥72 hours without dialysis between April 2013 and April 2021, were reviewed retrospectively. Treatment success was defined as defervescence and blood culture sterilization by day 7. Nephrotoxicity was defined as an increase in serum creatinine levels ≥0.3 mg/dL or a 50% increase from baseline on 2 consecutive days. Bayesian estimation was used to predict individual vancomycin AUC. Both classification and regression tree and receiver operating characteristic curve analyses were performed to estimate the optimal AUC thresholds for vancomycin efficacy and nephrotoxicity. Results: Of 118 patients, 61 (51.7%) experienced treatment failure and 42 (35.6%) developed acute kidney injury. The vancomycin AUC threshold for predicting acute kidney injury was 615.0 mg· hr/L. In the multivariate analysis, AUC ≥615.0 mg· hr/L was a significant risk factor for nephrotoxicity (adjusted odds ratio [aOR] = 5.24; 95% CI, 1.8-14.65). The lower threshold for treatment failure was not defined because it was not statistically significant. Risk factors for treatment failure included low body mass index (aOR = 0.82; 95% CI, 0.70-0.96), severity of acute illness represented by complicated infection (aOR = 77.56; 95% CI, 16.7-359.4) and comorbidities, such as solid organ tumors (aOR = 6.61; 95% CI, 1.19-36.81) and cerebrovascular disease (aOR = 6.05; 95% CI, 1.17-31.23). Conclusions: Although AUC-guided vancomycin dosing was associated with a reduced risk of acute kidney injury, its ability to predict clinical outcomes was modest. Further studies are needed to define the AUC therapeutic range to maximize efficacy and minimize nephrotoxicity. (Curr Ther Res Clin Exp. 2023; 83:XXX-XXX).

HOMA-estimated insulin resistance as an independent prognostic factor in patients with acute pancreatitis.

This prospective study investigated the relationship between insulin resistance assessed using the homeostatic model assessment of insulin resistance (HOMA-IR) and the prognosis of acute pancreatitis (AP). A total of 269 patients with AP were recruited in this study. HOMA-IR scores were calculated using fasting insulin and plasma glucose levels. Patients were then categorized into the non-insulin-resistant group (HOMA-IR <2.5) and the insulin-resistant group (HOMA-IR ≥2.5). We performed multivariable logistic regression analysis to investigate the independent association between IR assessed using HOMA-IR and the severity of AP. We also conducted receiver operating characteristic analysis to investigate the predictive ability of HOMA-IR for severe AP. The proportion of patients with severe AP (according to the Atlanta classification) and the percentage of ICU admissions and mortality were higher in patients with insulin resistance than in those without insulin resistance. The area under the curve (AUC) of HOMA-IR for predicting severe AP was 0.719 (95% CI 0.59-0.85, P = 0.003). This value was not significantly different from the AUCs of other AP scoring systems such as CTSI, Ranson, and BISAP. Insulin resistance was the only independent factor for either ICU admission (OR 5.95, 95% CI 1.95-18.15, P = 0.002) or severe AP (OR 6.72, 95% CI 1.34-33.62, P = 0.020). Our findings suggest that the HOMA-IR score is an independent prognostic factor in patients with acute pancreatitis. This finding indicates that insulin resistance is potentially involved in the mechanism for severe AP.

Primary Bone Marrow B-Cell Lymphoma Undetected by Multiple Imaging Modalities That Initially Presented with Hypercalcemia.

PURPOSE: We report a rare case of severe hypercalcemia that was ultimately diagnosed as primary bone marrow diffuse large B-cell lymphoma (BCL). CASE REPORT: A 74-year-old male patient visited our hospital complaining of tenderness and swelling of the left knee caused by supracondylar fracture of the left distal femur. His initial blood tests showed a serum calcium level of 13.9 mg/dL, inorganic phosphorus of 4.34 mg/dL, and a serum creatinine level of 1.54 mg/dL. A serum assay of intact parathyroid hormone showed 5.24 pg/mL, and the patient's serum 25(OH)D level was 22.33 ng/mL. To exclude malignancy, we performed imaging studies, including abdomen or chest computed tomography and positron emission tomography-computed tomography; however, no suspicious lesion was found, although the serum PTH-related peptide level was elevated at 4.0 pmol/L. A bone marrow biopsy was performed to identify any hidden hematologic malignancy. As a result, the pathology of bone marrow confirmed the presence of atypical lymphocytes that stained positive for the CD20 marker, which is consistent with BCL involving the bone marrow. CONCLUSION: This case highlights the importance of pursuing a thorough workup for rare underlying causes of hypercalcemia when parathyroid-related etiologies can be excluded.

Association between OH/ECW and echocardiographic parameters in CKD5 patients not undergoing dialysis.

BACKGROUND: Echocardiography is the most valuable tool for assessing cardiac abnormalities of chronic kidney disease (CKD) patients even though it has its limitations, including high equipment cost and the need for specialized personnel. Assessment of volume status is important not only for volume management, but also for prevention of cardiovascular disease of the CKD patients. Recently, bioimpedance is gaining acceptance as a way to quantitatively assess patient hydration status at bedside. METHODS: 127 patients who were admitted for planning their first dialysis treatment were enrolled. The echocardiography and bioimpedance spectroscopy (BIS) were performed. The association between echocardiographic data and clinical values such as NT-proBNP and OH/ECW was examined. RESULTS: OH/ECW, which indicates relative fluid overload, was positively associated with LA dimension (r = 0.25, P = 0.007), LAVI (r = 0.32, P < 0.001), and E/e´ ratio (r = 0.38, P < 0.001). While OH/ECW was not significantly associated with echocardiographic values such as LVEDD, LVEDV, LVMI, and LVEF, NT-proBNP were significantly associated with all echocardiographic parameters. Multivariate logistic regression analysis showed E/e´ ratio (odds ratio, 1.14 [95% confidence interval (CI), 1.01 to 1.29]; P = 0.031), NT-proBNP (odds ratio, 4.78 [95% CI, 1.51 to 15.11]; P = 0.008), and albumin (odds ratio, 0.22 [95% CI, 0.08 to 0.66]; P = 0.007) were significantly associated with OH/ECW. CONCLUSIONS: Since OH/ECW measured by BIS is associated with echocardiographic parameters related to diastolic dysfunction, preliminary screening through laboratory findings, including serum albumin in conjunction with OH/ECW and NT-proBNP, may find patient with risk of diastolic dysfunction. Our study suggests that a timely detection of fluid overload in patients with CKD as well as their proper treatment may help reduce diastolic dysfunction. Further research may be needed to validate the consistency of this association across other stages of CKD.

Association between E/e´ ratio and fluid overload in patients with predialysis chronic kidney disease.

BACKGROUND: Chronic fluid overload is common in patients with chronic kidney disease (CKD) and can with time lead to diastolic dysfunction and heart failure. We investigated whether markers of fluid status, such as NT-proBNP and bioimpedance spectroscopy (BIS), can predict echocardiographic findings of diastolic dysfunction in non-dialysis CKD5 patients. METHODS: BIS, echocardiography, and measurement of serum NT-proBNP were performed in patients with non-dialysis CKD stage 5 at a single study visit. E/e´ ratio reflect mean LV diastolic pressure and a ratio greater than 15 was used as a definition of diastolic dysfunction. RESULTS: Eighty-four patients were analyzed. Forty-six patients (54.76%) had E/e´ ratio ≤15 and 38 patients (45.24%) had E/e´ > 15 (diastolic dysfunction). Patients with E/e´>15 had significantly higher serum NT-proBNP (14,650 pg/mL) than patients with to E/e´≤15 (4,271 pg/mL) and had more overhydration (OH), 5.1 liters compared to 2.4 liters. The cut-off values predicting diastolic dysfunction were found to be 2,797 pg/mL for NT-proBNP and 2.45 liters for OH. CONCLUSIONS: Regular monitoring of fluid status by BIS and NT-proBNP can be used to find patient with risk of developing diastolic dysfunction. Treatments to correct fluid overload may reduce the risk of developing diastolic dysfunction and improve cardiovascular outcome in patients with CKD.

Formulation and Management of Poor Bowel Preparation: A Survey Study.

BACKGROUND/AIMS: There are no established guidelines for bowel preparation formulation for bowel cleansing, nor is there an optimal method of dealing with inadequate bowel cleansing. This study investigated bowel preparation formulation preferences and responses to bowel preparation situations using surveys. METHODS: The study surveyed 221 Korean lower gastrointestinal endoscopists from January to March 2015 and assessed their responses. RESULTS: The analysis indicated that 2-L polyethylene glycol (PEG) plus ascorbic acid (Asc) was the preferred method (76.5%) and most responders expressed satisfaction with the formulation in both potency and safety. To address poor bowel preparation on the day of colonoscopy, the majority of physicians chose to order ingestion of additional preparations and proceed with the colonoscopy as scheduled (56.6%). In addition, concerns about renal safety and electrolyte stability were raised regarding oral sodium phosphate. CONCLUSIONS: This study found that 2-L PEG+Asc was preferred for potency and safety, and that Korean endoscopists preferred to proceed with colonoscopy in poor bowel preparation situations rather than choose an alternate diagnostic modality.

Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report.

Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus.

A Case of Splenic Tuberculosis Forming a Gastro-splenic Fistula.

We report a case of a 61-year-old man who presented with a cough and abdominal discomfort. CT scan of the chest showed two lesions across both lungs, and an abdominal CT scan revealed multiple hypodense lesions in the spleen with cystic lesions on the splenic hilum. Upper gastrointestinal tract endoscopy found creamy yellowish discharge through a fistula between the stomach and splenic hilum. Under fluoroscopic guidance, forceps was inserted into the fistula tract, and forcep biopsy was done. The pathology was consistent with tuberculosis, and a nine-month anti-tuberculosis medication regimen was started. Imaging performed three months after finishing medication indicated improvement of splenic lesions, and the gastro-splenic tract was sealed off. This case is a very rare clinical example of secondary splenic tuberculosis with a gastro-splenic fistula formation in an immunocompetent patient.

Differences in Adipokine and Hepatokine Levels among Non-diabetic Population Classified by Age and Sex.

BACKGROUND: Leptin, angiopoietin-related growth factor (AGF), adiponectin (ADP), and retinol-binding protein 4 (RBP4) are cytokines associated with the development of metabolic disorders, such as type 2 diabetes and cardio vascular disease. However, the levels of these cytokines have not extensively studied in non-diabetic subjects. Therefore, we analyzed the differences in these cytokine levels according to sex and age in non-diabetic Korean population. METHODS: Blood samples were collected from 59 non-diabetic Korean adults (male, 32; female, 27). The anthropometric and biochemical data were measured at the health examination center. Serum adipokines and hepatokines were measured by enzyme linked immunosorbent assay (ELISA). The data were analyzed according to sex and age-based quartiles. RESULTS: Serum leptin values were higher in females (8.60 ± 3 µg/ml) compared with males (2.99 ± 2.9 µg/ml). However, RBP4 was higher in males (84.05 ± 47.04 µg/ml) than in females (61.25 ± 45.42 µg/ml). The AGF and ADP values were not significantly different between males and females. RBP4 level was inversely correlated with age quartile in males, while leptin was significantly associated with body mass index and insulin resistance. CONCLUSION: RBP4 and AGF levels showed age-associated change, and leptin was consistently higher in females. Therefore, a large-scale analysis to determine the normal range of adipokines and hepatokines concentration in healthy Korean population is necessary. When interpreting adipokine and hepatokine levels, the difference in age and sex needs to be taken into account.