Evaluating antimicrobial utilization in 20 Korean long-term care hospitals: a call to action for antimicrobial stewardship.

BACKGROUND: Evaluation of hospital-specific antimicrobial use is necessary for successful national antimicrobial stewardship. This study aimed to identify antimicrobial use in long-term care hospitals (LCHs) in Korea. METHODS: A multi-centre retrospective study was conducted to evaluate the prescription patterns and appropriateness of antimicrobials in 20 LCHs in Korea. The medical record data of hospitalized patients who were newly prescribed antimicrobials at each hospital were collected manually between 10th July and 31st October 2023 to evaluate the appropriateness of antimicrobial use. RESULTS: The prevalence of antimicrobial prescriptions was 8.9% (365/4086) and 10.3% (402/3892) on 12th July 2023 and 18th October 2023, respectively. In total, 885 antimicrobials were prescribed to 740 patients. Among the antimicrobials, third- or fourth-generation cephalosporins (31.9%) represented the most prescribed antimicrobial class. A large majority of antimicrobials (96.6%, 855/885) were prescribed for the treatment of infectious diseases; however, only 37.7% (322/855) of antimicrobials were prescribed appropriately for infections. The route of administration, dosage and prescribed antimicrobial were appropriate in 99.6% (852/855), 56.1% (480/855) and 62.0% (530/855) of cases, respectively. In total, 35.2% (252/715) of patients were prescribed antimicrobials appropriately. The diagnosis of infectious disease was appropriate for 52.9% (472/892) of cases. Of the five, 15 and 10 antimicrobials used for surgical site infection prophylaxis, medical prophylaxis and other purposes, respectively, none were used appropriately. CONCLUSION: The proportion of antimicrobials used appropriately is low in Korean LCHs. These data highlight the importance of establishing antimicrobial stewardship in LCHs.

Seven Years of Experiences of Preclinical Experiments of Xeno-Heart Transplantation of Pig to Non-Human Primate (Cynomolgus Monkey).

BACKGROUND: The absolute shortage of donors compared with patients requiring transplantation is currently an unsolved problem, and the only possible solution may be xenotransplantation. To establish a successful clinical trial, a preclinical study using nonhuman primates is essential. Starting in November 2011, our team initiated heterotopic abdominal heart xenotransplantation, the first in the Republic of Korea. We present here the initial 7-year results. METHODS: A total of 22 xenotransplantation procedures have been performed since 2011. Single transgenic pig (alpha-galactosidase transferase knockout [GalT KO], n = 16), double transgenic pig (GalT KO + CD46, n = 3, and GalT KO + CD39, n = 2), and triple transgenic pig (GalT KO + CD46 + CD70, n = 1) models were used. Our baseline regimen of immunosuppressants comprised CD154 ab, rituximab, anti-thymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The mean graft survival was 16 ± 16.27 days, and the mean graft survival was significantly longer in cases performed since 2014 (7.5 ± 8.03 days vs 24.67 ± 17.50; P = .01). Although the donor heart ischemic time was decreased per annum, no correlations could be found between ischemic time and survival days of the graft. Double or triple genetic manipulated hearts exhibited significantly better survival (11.63 ± 11.29 days vs 30.83 ± 20.34 days; P = .03). When the ratio of heart weight (grams) to nonhuman primate weight (kilograms) was lower, the results tended to be better (P < .05). The rate of immediate postoperative bleeding (9%, n = 2) causing death was relatively high in the earlier period, but there have been no serious surgical complications affecting graft survival since 2013. CONCLUSIONS: Investigation of effective and optimal target genes for each organ to further progression toward better results is important. In addition, the immunosuppressive regimen needs to be further studied and constantly refined.

Outcomes of alpha 1,3-GT-knockout porcine heart transplants into a preclinical nonhuman primate model.

BACKGROUND: Solid organ xenotransplantation is a potential solution to current organ shortages in allotransplantation. We performed four heart transplantations from alpha1, 3-galactosyltransferase gene-knockout (GT-KO) pigs to cynomolgus monkeys and monitored immunological parameters before and after transplantation. METHODS: After blood typing of the cynomolgus monkeys, we assessed the binding activity of immunoglobulin G (IgG) and IgM of monkey serum and serum toxicity toward porcine peripheral blood mononuclear cells (PBMCs) using flow cytometry. Immunosuppressive protocols consisted of anti-thymocyte globulin (25 mg/kg), rituximab (20 mg/kg), anti-CD154mAb (20 mg/kg), cobra venom factor (0.05 mg/kg), tacrolimus, and steroid. Cynomolgus monkeys with A or AB blood type with the lowest antibody binding and serum toxicity activity on porcine PBMCs were selected as recipients. RESULTS: Absolute numbers of CD3(+) T cells, CD20(+) B cells, and CD3(+)CD95(+) memory T cells in the peripheral blood were suppressed upto 24 days after transplantation. Interferon gamma production of T cells in response to porcine antigens were also significantly suppressed. Heart xenografts from GT-KO pigs survived for upto 24 days without pathologic evidence of rejection. CONCLUSION: We successfully performed 4 heart xenotransplantations using GT-KO pigs. We overcame hyperacute rejection by using GT-KO pigs, and all of the heart xenografts from the GT-KO pigs survived between 11 and 24 days without pathologic evidence of rejection, disseminated intravascular coagulation, or consumptive coagulopathy; however, we need to optimize protocols for immune modulation and postoperative care to attain long-term survival of solid organ xenografts.

Endovenous laser ablation of the incompetent small saphenous vein with a 980-nm diode laser: our experience with 3 years follow-up.

PURPOSE: To demonstrate the long-term treatment outcomes of endovenous laser ablation (EVA) of incompetent small saphenous veins (SSV) with a 980-nm diode laser. MATERIALS AND METHODS: Eighty-four patients (96 limbs), with varicose veins and reflux in the SSV on duplex ultrasound examination, were treated with a 980-nm diode laser under ultrasound- or fluoroscopy-guidance. Patients were evaluated at 1 week and 1, 3, 6 months, 1 year and yearly thereafter. RESULTS: In the 96 limbs, the technical success rate was 100%. The SSV remained closed in 89 of 93 limbs (96%) after 1 month, all of 82 limbs after 6 months, 77 limbs after 1 year, 71 limbs after 2 years and 55 limbs after 3 years. In four limbs where recanalisation was observed, repeat EVA was done resulting in successful obliteration of the SSV. No major complication occurred however bruising (27%), tightness or pain (13%) and paraesthesia (4.2%) were observed. CONCLUSION: Endovenous laser ablation with a 980-nm laser wavelength is an easy and safe procedure in incompetent SSVs. After successful treatment, there is a very low rate of recanalisation of the SSV, which suggests that the procedure will provide lasting results.

Gene delivery into rat glomerulus using a mesangial cell vector.

To develop an effective protocol of gene transfer into glomeruli, an ex vivo gene delivery system using rat mesangial cells (RMC) as a vector was examined. RMC genetically engineered with a retrovirus harboring the Escherichia coli beta-galactosidase gene was used to estimate the efficacy of gene delivery and the location of the cells within the kidney. The RMC expressing beta-galactosidase, RMCLZ1, was cultured in vitro and the cells were injected into the left kidney through the renal artery of a normal Sprague Dawley rat. At least 1 x 10(6) RMCLZ1 was required for effective gene delivery into glomeruli. One hour and 1, 4, and 14 d after injection, glomeruli were isolated from the left kidneys injected with the cells and the expression of beta-galactosidase in each glomeruli was evaluated. One hour and 1 d after injection, more than 90 and 80%, respectively, of glomeruli from the left kidney showed strong beta-galactosidase activity, while no activity of beta-galactosidase was found in the glomeruli from the right kidneys. The number of glomeruli stained by X-gal and the intensity decreased with time. Fourteen days after injection, about 35% of the glomeruli retained the RMCLZ1. X-gal and periodic acid-Schiff staining of frozen sections obtained 14 d after injection allowed the estimation of the site where the mesangial cells injected were located. The mesangial cells were found mainly in two different locations, the glomerular capillary and the mesangium. The majority (about 90%) of the mesangial cells were located in the glomerular capillary and about 9% of the cells were in the mesangial area. Occasionally, the positive staining was found in proximal tubules and the interlobular artery. Although additional methods are required for the site-specific targeting of the mesangial area, the ex vivo gene transfer to glomeruli is feasible and may be a useful tool for future investigations in the pathological mechanisms of glomerular injury.

Detection of cancer in augmented breasts by positron emission tomography.

OBJECTIVE: To assess the diagnostic efficiency of positron emission tomography with 18-fluorine fluorodeoxyglucose in detecting breast cancer in augmented breasts. DESIGN: Retrospective study. SETTING: University hospital, Korea. SUBJECT: 9 cases or 8 patients with breasts augmented with paraffin or silicone. INTERVENTION: FDG-PET, mammography, and ultrasonography RESULTS: The mammogram detected the breast cancer in only 1 of 3 patients, and ultrasonography gave a false positive result in 1 patient with an augmented breast. In contrast, PET predicted all the cancers and 5/6 benign lesions. 2/3 breast cancers had axillary FDG uptake interpreted as showing metastatic involvement, and in 1 case with cancer with no axillary lymph node involvement there was no FDG uptake in the axilla, which correlated with the pathological finding. CONCLUSIONS: Although the high cost of PET makes its use as a screening test for all patients with augmented breasts unrealistic, it would be the best diagnostic choice if other methods failed.

Effect of protease inhibitor on ischemia-reperfusion injury to rat liver.

Liver failure due to ischemia-reperfusion injury, believed to be closely related to the generation of oxygen-free radicals, is a serious problem during liver surgery. Gabexate mesilate, a synthetic protease inhibitor, suppresses the extracellular release of oxygen-free radicals in the microvascular endothelium. To determine its effects on ischemia-reperfusion injury to the liver, we performed experiments with rats. We divided the animals into two ischemia-reperfusion groups: an experimental group, which underwent ischemic injury for 30 minutes, along with the infusion of gabexate mesilate, and a control group, which underwent injury only. Each group was then divided into four subgroups: ischemic injury only and 60-, 120-, and 180-minute reperfusion injury. The test parameters were tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) in serum and superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) in liver and lung tissues. The experimental group had a significantly higher liver SOD and catalase levels and a significantly lower level of liver and lung MDA than the control groups. TNFalpha levels in the experimental groups were significantly lower during the early phase, but a comparison of IL-6 levels between the two groups yielded no differences. Levels of lung catalase and SOD were not significantly different between the two groups. We concluded that protease inhibitor suppressed liver ischemia-reperfusion injury, and that it was due to an increase of antioxidant or suppression of oxygen-free radicals. The roles of TNFalpha and IL-6 in liver reperfusion injury were not clear, though TNFalpha might have had an effect during the early phase. With liver ischemia-reperfusion injury, the mechanism of lung involvement might be different from that of liver involvement.

Diagnostic value of positron emission tomography for detecting breast cancer.

Positron emission tomography (PET) is an imaging method that employs radionuclide and tomography techniques. PET has high sensitivity for detecting breast cancer, both the primary tumor and axillary node metastasis. From June 1995 to November 1996 a total of 27 patients underwent breast operations based on PET results at Seoul National University Hospital. Whole-body PET images were obtained beginning 60 minutes after injection of 370 MBq (10 mCi) 18F-fluorodeoxyglucose. Regional scans were also obtained with transmission images. We compared the PET results with those from the physical examination and mammography. All cases were histologically confirmed. The diagnostic accuracy of PET was excellent for the primary tumor mass (97%) compared with that of the physical examination (78%) and mammography (67%). For axillary lymph node metastasis, PET had outstanding detection accuracy (96%) compared with the physical examination and mammography (74% and 60%, respectively). Whole-body PET scans made it possible to see all of the metastatic lesions at a glance in cases of metastatic or recurrent breast cancer. There was a probable correlation between the standard uptake value (SUV) and the number of axillary lymph node metastases, but in this study statistical significance was not proved because of the small number of cases. PET also could detect breast cancer in paraffin-augmented breasts. We concluded that PET is a highly sensitive, accurate diagnostic tool for breast cancer and that SUV, after more studies, could be used as an important prognostic factor.

Abnormal expression of four novel molecular markers represents a highly aggressive phenotype in breast cancer. Immunohistochemical assay of p53, nm23, erbB-2, and cathepsin D protein.

BACKGROUND: In view of the cumulative results to date, p53, nm23, erbB-2, and cathepsin D are the most promising investigational prognostic factors in breast cancer. OBJECTIVES: The clinical utility of these molecular markers to predict recurrence was evaluated. METHODS: Archival pathology tissues of 100 breast cancer patients were analyzed by immunohistochemical assay. Molecular biologic data were merged with clinicopathologic variables. RESULTS: Thirty-two patients (32%) had recurrence of disease at a median follow-up of 48 months (range 26-72 months). Investigational factor expression had statistical correlation for recurrence with increasing coexpression: one variable 20.6%, two variables 34.2%, three variables 47.1%, four variables 80.0% (P = 0.003). In univariate analysis, lymph node metastasis, tumor size, erbB-2 protein overexpression, and loss of nm23 protein expression were significant variables to determine recurrence; in multivariate analysis, node status and tumor size emerged as the most significant variables for recurrence. CONCLUSIONS: Coexpression of the studied investigational variables functioned as significant prognostic correlates for recurrence. These findings suggest that the studied investigational prognostic factors possess the ability to discriminate a highly aggressive phenotype in breast cancer.

Menstrual and reproductive factors related to the risk of breast cancer in Korea. Ovarian hormone effect on breast cancer.

To support the ovarian hormone hypothesis in the etiology of breast cancer, a hospital-based case-control study with community controls was conducted to evaluate the relationship of intervals among menstrual and reproductive events to the risk of breast cancer in Korea. The cases were 190 breast cancer patients, who had been histologically diagnosed at Seoul National University Hospital from Jan. 1, 1993 to Jun. 30, 1994. Included were cancer-free women, who had undertaken the Gynecological examination at the same hospital (n=190). Women recruited for a survey of diabetes prevalence in Yonchon County, adjacent to Seoul City, were taken as a community control group (n=190). Information on menstrual and reproductive factors with other life-styles was collected through a direct interview by the well-trained interviewers. The adjusted odds ratios and the 95% confidence intervals were based on the unconditional logistic regression model. Likelihood ratio test for trend was applied for the ordinal variables. Early age at menarche, late age at natural menopause, late age at first full term pregnancy, and fewer number of full term pregnancies are independently associated with the high risk of breast cancer in Korea. Moreover, the interval between the age at menarche and the age at natural menopause of community controls (29.9+/-6.15 years) was significantly shortened compared to breast cancer cases (34.9+/-4.42 years). Particularly noteworthy was that intervals between the age at menarche and the age at first full term pregnancy of both control groups (9.0+/-3.72 years for hospital controls; 7.2+/-4.04 years for community controls) were significantly shortened compared to breast cancer cases (11.0+/-4.51 years). These findings support the hypothesis that the longer exposure to ovarian hormones during the reproductive years, the higher the risk of breast cancer.