Short-term Rosuvastatin Treatment for the Prevention of Contrast-induced Acute Kidney Injury in Patients Receiving Moderate or High Volumes of Contrast Media: A Sub-analysis of the TRACK-D Study

Background:

Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI). However, the consistency of these effects on patients administered different volumes of contrast media is unknown.

Methods:

In the TRACK-D trial, 2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV], 200–300 ml, n = 712) or (high contrast volume [HCV], ≥300 ml, n = 220). The primary outcome was the incidence of CIAKI. The secondary outcome was a composite of death, dialysis/hemofiltration or worsened heart failure at 30 days.

Results:

Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P = 0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029), whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834). The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P = 0.081) or HCV (5.1% vs. 8.8%, P = 0.273).

Conclusions:

Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.     

Chronic treatment with the monoamine oxidase inhibitor phenelzine increases hypothalamic-pituitary-adrenocortical activity in male C57BL/6 mice: relevance to atypical depression

Atypical depression has been linked to low hypothalamic-pituitary-adrenocortical axis activity and exhibits physical and affective symptoms resembling those of glucocorticoid deficiency. Because atypical depression has also been defined by preferential responsiveness to monoamine oxidase inhibitors (MAO-I), we hypothesized that MAO-I reverse these abnormalities by interfering with glucocorticoid feedback and increasing hypothalamic-pituitary-adrenocortical activity. To test this hypothesis, we measured plasma hormones and ACTH secretagogue gene expression in male C57BL/6 mice treated chronically with saline vehicle or phenelzine, a representative MAO-I. Changes in glucocorticoid feedback were evaluated using adrenalectomized (ADX) mice with and without corticosterone replacement. Antidepressant efficacy was confirmed by decreased immobility during forced swim testing. Phenelzine significantly increased circadian nadir and postrestraint plasma corticosterone levels in sham-operated mice, an effect that correlated with increased adrenocortical sensitivity to ACTH. Phenelzine increased circadian nadir, but not poststress ACTH in ADX mice, suggesting that phenelzine augmented corticosterone secretion in sham-operated mice by increasing stimulation and decreasing feedback inhibition of hypothalamic-pituitary activity. Consistent with the latter possibility, phenelzine significantly increased plasma ACTH and paraventricular hypothalamus CRH mRNA in ADX, corticosterone-replaced mice. Phenelzine did not increase paraventricular hypothalamus CRH or vasopressin mRNA in ADX mice lacking corticosterone replacement. We conclude that chronic phenelzine treatment induces sustained increases in glucocorticoids by impairing glucocorticoid feedback, increasing adrenocortical responsiveness to ACTH, and increasing glucocorticoid-independent stimulation of hypothalamic-pituitary activity. The resulting drive for adrenocortical activity could account for the ability of MAO-I to reverse endocrine and psychiatric symptoms of glucocorticoid deficiency in atypical depression.     

Recent increase in antibiotic-resistant microorganisms in patients with spontaneous bacterial peritonitis adversely affects the clinical outcome in Korea

BACKGROUND AND AIM: Recently, antibiotic-resistant microorganisms have been increasingly noted in Korean patients with spontaneous bacterial peritonitis (SBP). The present study investigated the changing pattern of antibiotic resistance and its effects on the clinical outcome in treating SBP. METHODS: The present study retrospectively analyzed 87 episodes of SBP in 1995, 222 in 1998, and 271 in 1999. The isolated microorganisms and their antibiotic susceptibility were compared, and prognostic factors for survival were analyzed. RESULTS: Microorganisms were isolated in 41% of total episodes. The three most frequently isolated organisms were Escherichia coli (48%), Klebsiella pneumoniae (15%), and Aeromonas (8%). Strains that were resistant to cefotaxime in Gram-negative bacilli significantly increased from 7% in 1995 to 28% in 1999, and those to ciprofloxacin increased from 10% to 32%. Treatment failure also increased from 6% to 23%. Combined hepatocellular carcinoma and SBP caused by extended-spectrum beta-lactamase-producing strains were two independent prognostic factors for survival. CONCLUSION: Considering the increase in antibiotic-resistant microorganisms related to SBP, measures to prevent the in-hospital spread of resistant strains and the indiscriminate use of antibiotics should be instituted more stringently.     

Neuropeptide release by efficient recruitment of diffusing cytoplasmic secretory vesicles

Neuropeptides are slowly released from a limited pool of secretory vesicles. Despite decades of research, the composition of this pool has remained unknown. Endocrine cell studies support the hypothesis that a population of docked vesicles supports the first minutes of hormone release. However, it has been proposed that mobile cytoplasmic vesicles dominate the releasable neuropeptide pool. Here, to determine the cellular basis of the releasable pool, single green fluorescent protein-labeled secretory vesicles were visualized in neuronal growth cones with the use of an inducible construct or total internal reflection fluorescence microscopy. We report that vesicle movement follows the diffusion equation. Furthermore, rapidly moving secretory vesicles are used more efficiently than stationary vesicles near the plasma membrane to support stimulated release. Thus, randomly moving cytoplasmic vesicles participate in the first minutes of neuropeptide release. Importantly, the preferential recruitment of diffusing cytoplasmic secretory vesicles contributes to the characteristic slow kinetics and limited extent of sustained neuropeptide release.     

Fat-forming solitary fibrous tumor of the kidney: a case report and literature review

Fat-forming solitary fibrous tumor (SFT) is a rare soft tissue tumor. Herein, we reported a 30-year-old woman was found to have a solid mass measuring 60×45 mm in the right kidney on an abdominal computed tomography scan. The tumor was well-circumscribed and composed of cellular nodules with the classic SFT admixed with clusters and lobules of mature adipocytes. Immunohistochemistry staining showed that the tumor cells were diffusely and strongly positive for CD34 and Bcl-2, focally and weakly positive for CD99 and EMA. Mature adipocytes were positive for S-100 protein. Ki-67 expression was found in approximately 2% of tumor cells. However, tumor cells were negative for cytokeratin, S-100 protein, HMB-45, Melan-A, SMA, and CD117. We made the pathological diagnosis of fat-forming SFT of the right kidney. The differential diagnosis includes angiomyolipoma, liposarcoma, spindle cell lipoma, sarcomatoid renal cell carcinoma, synovial sarcoma, and gastrointestinal stromal tumor. The patient was alive and well without evidence of recurrence or metastasis at 19 months after tumor resection.     

KyoT2 downregulates airway remodeling in asthma

The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson’s staining and Masson’s trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.     

Liposarcoma of the larynx: report of a case and review of literature

Liposarcomas of the larynx are extremely rare tumors, with only 37 cases reported in the English or French literature to date. The first two cases of laryngeal liposarcomas were reported respectively by Kapur and Dockerty in 1968 [1, 2]. Liposarcoma of the larynx is at high risk of local recurrence and seldom has metastatic potential. Prognosis for this tumor is better than that of non laryngeal liposarcoma. The present case is the first patient of primary liposarcoma of the larynx reported from China. A review of the literature was performed, and the presentation, position, pathological diagnosis, treatment and prognosis of the patients with liposarcoma of the larynx of the reported cases before are analyzed.     

Clinical significance of joint detection of serum CEA,SCCA, and bFGF in the diagnosis of lung cancer

Lung cancer is a type of malignant tumor with highest morbidity and mortality. This study tested three tumor marker levels including CEA, SCCA, and bFGF to explore their value in lung cancer diagnosis and pathological type judgment. Venous blood was extracted from lung cancer patients, lung benign lesion patients and healthy control. Electrochemiluminescence immunoassay was applied to detect serum CEA and SCCA content. ELISA was used to test serum bFGF level. Serum CEA, SCCA, and bFGF levels and positive rates were significantly higher in lung cancer group than that of lung benign disease group and health control (P < 0.05). bFGF showed higher detection sensitivity than CEA in lung cancer (P < 0.05). Three joint detection sensitivity was higher than single test (P < 0.05), while its specificity was lower (P < 0.05), and the accuracy presented no significant difference. Serum CEA and SCCA levels and positive rates were obviously higher in non-small cell lung cancer patients when compared with small cell lung cancer patients (P < 0.05), while bFGF level was similar between small cell lung cancer and non-small cell lung cancer. bFGF showed higher detection rate than SCCA in small cell lung cancer (P < 0.05). Three joint detection exhibited higher positive rate in small cell lung cancer and non-small lung cancer than single test. Serum CEA, SCCA and bFGF joint detection improved detection sensitivity in lung cancer and had important reference value for pathological type deduction.     

Assessment of the Safety and Efficacy of an Attenuated Live Vaccine Based on Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

The safety and efficacy of the JXA1-R vaccine, an attenuated strain of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV), were examined using an intramuscular challenge model in piglets. The JXA1-R vaccine was obtained by passing HP-PRRSV JXA1 through Marc-145 cells (82nd passage). Genomic sequence comparisons showed that strain JXA1-R and its parental strain, JXA1, differ by 47 amino acids, and most of these differences are scattered throughout the PRRSV genome. Four-week-old PRRSV-free piglets were inoculated intramuscularly with JXA1-R vaccine (10^3.0, 10^4.0, 10^5.0, 10^6.0, and 10^7.0 50% tissue culture infective doses [TCID₅₀]/ml for groups 1 to 5, respectively) and then challenged intramuscularly with the 5th passage virus of JXA1 virus (JXA1-F5, 3 ml × 10^4.5 TCID₅₀/ml) 28 days after inoculation. The humoral immune response, swine growth, clinical signs, and differential organ lesions were monitored. The results showed that all vaccinated piglets had a perceptible humoral immune response to vaccination after day 7, which then promptly increased, almost reaching the maximum sample/positive (S/P) ratio value at 28 days postimmunization. Viremia detection indicated that the viral replication levels of the challenge virus in the immunized groups (immunization doses ≥10^4.0/ml) were significantly lower than that of the virus-challenged unvaccinated control group. Piglets in groups 2 to 5 were effectively protected against lethal HP-PRRSV infection and did not show any obvious changes in body temperature or clinical signs of disease at any point during the experiment. However, two of five piglets in group 1 showed mild pathological lesions and transitory high fever. These results suggest that JXA1-R (TCID₅₀/ml ≥10^4.0) is sufficiently attenuated and can provide effective protection against the lethal wild-type HP-PRRSV.