Abstract We have previously found that dietary exposure to vitamin D (VD3) reverses the increase in endometrial cancer in obese Pten+/- mice. Since obesity also increases breast cancer risk and recurrence, this study investigated whether VD3 supplementation may inhibit development of mammary cancer in obese mice. As the protective effect of VD3 in the endometrium was not related to the estrogen receptor (ER), we pursued another potential pathway and determined whether VD3 reverses obesity-induced insulin resistance. Methods: Two mouse models were used: DMBA-treated C57BL/6 mice developing ER positive (ER+) mammary tumors, and Pten+/- mice which develop triple negative mammary tumors. C57BL/6 mice were wild type littermates of the Pten+/- mice. Mice in the two models were divided into four groups after weaning, and they were fed (a) AIN93G based control diet, (b) diet supplemented with 20K IU VD3, (c) obesity-inducing diet (OID), or (d) OID supplemented with 25K IU VD3. Results: OID induced insulin resistance and increased mammary tumorigenesis in both C57BL/6 and Pten+/- mice. VD3 significantly inhibited ER+ (p<0.05) and ER- (p<0.04) mammary cancer, but did not reverse the obesity-induced increase in cancer risk. Results obtained in the insulin tolerance test, however, indicated that VD3 prevented the development of insulin resistance in the OID fed obese C57BL/6 and Pten+/- mice. Conclusions: Dietary exposure to VD3 protects against development of ER+ and triple negative mammary cancer, but only in lean mice. VD3 supplementation also prevents insulin resistance in obese mice, but this is not sufficient to reduce mammary cancer risk in either C57BL/6 or Pten+/- mice Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1812. doi:10.1158/1538-7445.AM2011-1812
Objectives The addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations. Methods We conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs). Results A total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively. Conclusions ICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.
Formula feeding is an important risk factor for the development of necrotizing enterocolitis in preterm infants. The potential harmful effects of different preterm formulas on the developing intestinal tract remain incompletely understood. Here we demonstrate that feeding newborn mouse pups with various preterm formulas resulted in differing effects on intestinal inflammation, apoptosis, and activation of the pro-inflammatory transcription factor NFκB. 16S rRNA sequencing revealed that each preterm formula resulted in significant gut microbial alterations that were different from dam-fed controls. Formula feeding with EleCare and Similac Special Care caused greater intestinal injury compared to NeoSure. Pre-treatment with Lactobacillus rhamnosus GG ameliorated severity of intestinal injury from EleCare and Similac Special Care. Our findings indicate that not all preterm formulas are the same, and different formulations can have varying effects on intestinal inflammation, apoptosis, and microbiome composition.
Objective To enhance the levels of the clinical diagnosis and treatment of pituitary adenomas in the aged patients. Methods The clinical data of 46 aged patients with pituitary adenomas,who underwent surgery from January,2001 to January,2009,were analyzed retrospectively,including the disease course,clinical manifestation,immunohistochemical examination,complications before and after the operation and the data gained by following up. All the data were compared to those of 91 patients with pituitary adenomas,aged 45～59 years,serving as control group. Results The disease course was significantly longer and the occurrence rates of headache or dizziness,defect of visual field,macroadenoma,preoperative complication and nonfunctioning adenoma were significantly higher in the aged group than those in the control group(P0.05) . Most patients suffered from hypopituitarism and needed to be treated by the hormone and some patients even suffered from serious osteoporosis after the operation in the aged patients with pituitary adenomas. Conclusions Great attention should be pay to the aged patient with pituitary adenomas which should be diagnosed and treated as early as possible. The close following up and timely treatment of the postoperative complication is helpful to improving postoperative life quality in the aged patients with pituitary patients undergoing surgery.
To evaluate the effects of the perfusion of low molecular dextran via the splenic artery in portal azygous devascularization for portal hypertension in the prevention from portal vein thrombosis.A total of 92 patients with portal hypertension were randomly divided into a control group (46 cases) that received the extensive devascularization around the cardia, and a trial group (46 cases) that received the above-mentioned operation and the perfusion of low molecular dextran via the splenic artery. The incidence of portal vein thrombus after the operation and the preoperative and postoperative blood transfusion were observed and the results were analyzed and compared between the two groups.The incidence of thrombosis and blood transfusion were 26.1% (12/46) and CRBC 4~6 U respectively in the control group, while those were 4.3% (2/46) and CRBC 2~3 U respectively in the trial group. The differences were statistically significant (P < 0.05).The perfusion of low molecular dextran via the splenic artery in portal azygous devascularization for portal hypertension is effective and safe in the prevention from portal vein thrombosis.
Introduction: Clostridium difficile infection always manifests as diarrhea associated with antibiotic use. Nevertheless, extraintestinal infections caused by C. difficile are reported. The current report was on a case of C. difficile bacteremia in a 51-year-old male patient with appendiceal perforation and abscess as well as confirmed cirrhosis. Case Presentation: The patient was admitted to the infectious diseases department with repeated abdominal pain associated with fever. His anaerobic blood culture was positive for C. difficile two days after transarterial chemoembolization. The same toxin strain was isolated from stool four days later. Both of the two isolates were confirmed positive for toxin A (tcd A) and toxin B (tcd B) genes by polymerase chain reaction, and identified as ST3 by multiple locus sequence typing. The two strains showed the same susceptibility to the tested antibiotics. The patient was treated with vancomycin intravenously, and got remitted shortly after that. The patient was discharged with good general health conditions and followed up. Conclusions: A patient with C. difficile bacteremia presenting with appendiceal perforation and abscess as well as confirmed cirrhosis was described, and the microbiological and molecular biological analysis suggested that C. difficile strains isolated from blood came from gut. It is necessary that clinicians detect C. difficile and/or toxins in patients with long terms antibiotic therapy, in case of transformation of intestinal flora, which could cause the infection outside the intestinal tract.
Objective To compare the effects of Chinese Shang Ring circumcision versus traditional circumcision for adult male with redundant prepuce. Methods One hundred and ninety-eight patients with redundant prepuce were randomly divided into two groups.One hundred cases in the Shang Ring group received Chinese Shang Ring circumcision,while 98 cases in the traditional group received tradtioal circumcision. The operation duration,intraoperative blood loss,healing time,visual analogue scale( VAS) score,postoperative complications( exudation,dehiscence and edema),appearance satisfaction and life influence were observed in two groups. Results Compared with traditional group,Shang Ring group achieved shorter operation duration,less intraoperative blood loss,lower VAS score and higher appearance satisfaction rate( P 0. 05) as well as longer healing time and higher incidences of postoperative edema,exudation and dehiscence( P 0. 05).Conclusion Chinese Shang Ring circumcision has favorable effects with the advantages of simple operation,shorter operation duration,less blood loss and better postoperative appearance. However,it presents the high incidences of postoperative edema,exudation and wound dehiscence as well as long healing time.
ObjectivesTo study the clinical relevance, mechanisms, and evolution of polymyxin B (POLB) heteroresistance in carbapenem-resistant Klebsiella pneumoniae (PHR-CRKP), potentially leading to a significant rise in POLB full resistant (FR) CRKP.Methods544 CRKP isolates from 154 patients treated with POLB were categorized into PHR and NHR (POLB non-heteroresistance) groups. We conducted statistical analysis to compare clinical implications and treatment responses. We employed whole-genome sequencing, bioinformatics, and PCR to study the molecular epidemiology, mechanisms behind PHR, and its evolution into FR.ResultsWe observed a considerable proportion (118/154, 76.62%) of clinical undetected PHR strains prior to POLB exposure, with a significant subset of them (33/118, 27.97%) evolved into FR after POLB treatment. We investigated the clinical implications, epidemiological characteristics, mechanisms and evolutionary patterns of PHR strains in the context of POLB treatment. 92.86% (39/42) of patients had PHR isolates before FR, highlighting the clinical importance of PHR. ST15 exhibited a notably lower PHR rate (1/8, 12.5% vs. 117/144, 81.25%; P < 0.01). ST11 PHR strains showing significantly higher rate of mgrB mutations by endogenous insertion sequences in their resistant subpopulation (RS) compared to other STs (78/106, 73.58% vs. 4/12, 33.33%; P < 0.01). The mgrB insertional inactivation rate was lower in FR isolates than in the RS of PHR isolates (15/42, 35.71% vs. 84/112, 75%; P < 0.01), while the pmrAB mutation rate was higher in FR isolates than in the RS of PHR isolates (8/42, 19.05% vs. 2/112, 1.79%; P < 0.01). The evolution from PHR to FR was influenced by subpopulation dynamics and genetic adaptability due to hypermutability.ConclusionsWe highlight significant genetic changes as the primary driver of PHR to FR in CRKP, underscoring polymyxins complexity. To study the clinical relevance, mechanisms, and evolution of polymyxin B (POLB) heteroresistance in carbapenem-resistant Klebsiella pneumoniae (PHR-CRKP), potentially leading to a significant rise in POLB full resistant (FR) CRKP. 544 CRKP isolates from 154 patients treated with POLB were categorized into PHR and NHR (POLB non-heteroresistance) groups. We conducted statistical analysis to compare clinical implications and treatment responses. We employed whole-genome sequencing, bioinformatics, and PCR to study the molecular epidemiology, mechanisms behind PHR, and its evolution into FR. We observed a considerable proportion (118/154, 76.62%) of clinical undetected PHR strains prior to POLB exposure, with a significant subset of them (33/118, 27.97%) evolved into FR after POLB treatment. We investigated the clinical implications, epidemiological characteristics, mechanisms and evolutionary patterns of PHR strains in the context of POLB treatment. 92.86% (39/42) of patients had PHR isolates before FR, highlighting the clinical importance of PHR. ST15 exhibited a notably lower PHR rate (1/8, 12.5% vs. 117/144, 81.25%; P < 0.01). ST11 PHR strains showing significantly higher rate of mgrB mutations by endogenous insertion sequences in their resistant subpopulation (RS) compared to other STs (78/106, 73.58% vs. 4/12, 33.33%; P < 0.01). The mgrB insertional inactivation rate was lower in FR isolates than in the RS of PHR isolates (15/42, 35.71% vs. 84/112, 75%; P < 0.01), while the pmrAB mutation rate was higher in FR isolates than in the RS of PHR isolates (8/42, 19.05% vs. 2/112, 1.79%; P < 0.01). The evolution from PHR to FR was influenced by subpopulation dynamics and genetic adaptability due to hypermutability. We highlight significant genetic changes as the primary driver of PHR to FR in CRKP, underscoring polymyxins complexity.
Objectives: To elucidate the association between anion gap (AG) and in-hospital mortality in intensive care patients with liver failure.Methods: Demographic and clinical characteristics of intensive care patients with liver failure in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were collected, and binomial logistic and Cox regression was conducted to investigate the association between AG and in-hospital mortality.The area under the receiver operating characteristic (ROC) curve (AUC) was conducted to characterize the performance of AG in predicting in-hospital mortality, and was compared with the albumin corrected anion gap (ACAG) and the End-Stage Liver Disease (MELD) score.The Kaplan-Meier curve was plotted for in-hospital survival analysis of AG and patients with liver failure.The propensity score matching (PSM) analysis was performed to mitigate selection bias.Results: AG was an independent risk factor for in-hospital mortality in intensive care patients with liver failure.Before PSM, the AUCs of AG, ACAG, and MELD were 0.666, 0.682, and 0.653, respectively.After PSM, the AUCs of AG, ACAG, and MELD scores were 0.645, 0.657, and 0.645, respectively, and there is no difference in the predictive performance of the three indicators upon comparison.Compared with the low-AG (≤20 mmol/L) group, the hazard ratio (HR) for in-hospital death of the high-AG (>20 mmol/L) group was determined to be 2.1472 (before PSM)/1.8890(after PSM).Conclusions: AG is associated with in-hospital mortality in intensive care patients with liver failure and demonstrates a moderate predictive value, which is comparable to the predictive power of the MELD score.AG may serve as an indirect marker of in-hospital mortality of patients with liver failure by reflecting the degree of metabolic acidosis.
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