Imatinib administration in two patients with liver metastases from GIST and severe jaundice

Imatinib is the only effective and approved systemic therapy for the treatment of patients with advanced gastrointestinal stromal tumours (GISTs). Although metastases from GISTs most commonly involve the liver, yielding hyperbilirubinaemia, very few data on imatinib administration in subjects with jaundice are available. We provide evidence that imatinib tolerability was not adversely affected by jaundice in two patients with advanced GIST.     

Effect of vancomycin initial dosing on time to systemic inflammatory response syndrome resolution in patients with methicillin-resistant Staphylococcus aureus bacteremia

Current guidelines suggest using vancomycin-loading doses for complicated infections despite a lack of evidence to support this practice. To address this gap, we performed a single-centre cohort study of 124 patients with sepsis due to methicillin-resistant Staphylococcus aureus bacteremia. Patients were allocated into two groups based on initial dose of vancomycin, <20 mg/kg or ≥20 mg/kg, and evaluated for time to resolution of systemic inflammatory response syndrome (SIRS). Among a cohort of 124 patients, 87 received vancomycin initial doses <20 mg/kg and 37 received ≥20 mg/kg. The median time to SIRS resolution was 109 h in the <20 mg/kg group compared to 67 h in the ≥20 mg/kg group. Cox proportional hazard modelling showed a faster resolution of SIRS in the ≥20 mg/kg group (HR = 1.72[1.09–2.73]). Vancomycin initial doses of ≥20 mg/kg led to faster resolution of SIRS although further studies are needed to evaluate the safety and efficacy of this approach.     

A pilot study of systemic corticosteroid administration in conjunction with intrapleural adenoviral vector administration in patients with malignant pleural mesothelioma

One of the primary limitations of adenoviral (Ad) -mediated gene therapy is the generation of anti-Ad inflammatory responses that can induce clinical toxicity and impair gene transfer efficacy. The effects of immunosuppression on these inflammatory responses, transgene expression, and toxicity have not yet been systematically examined in humans undergoing Ad-based gene therapy trials. We therefore conducted a pilot study investigating the use of systemic corticosteroids to mitigate antivector immune responses. In a previous phase I clinical trial, we demonstrated that Ad-mediated intrapleural delivery of the herpes simplex virus thymidine kinase gene (HSVtk) to patients with mesothelioma resulted in significant, but relatively superficial, HSVtk gene transfer and marked anti-Ad humoral and cellular immune responses. When a similar group of patients was treated with Ad.HSVtk and a brief course of corticosteroids, decreased clinical inflammatory responses were seen, but there was no demonstrable inhibition of anti -Ad antibody production or Ad-induced peripheral blood mononuclear cell activation. Corticosteroid administration also had no apparent effect on the presence of intratumoral gene transfer. Although limited by the small numbers of patients studied, our data suggest that systemic administration of steroids in the context of Ad-based gene delivery may limit acute clinical toxicity, but may not inhibit cellular and humoral responses to Ad vectors.     

Pneumococcal bacteremia in patients with neoplastic diseases

To evaluate the morbidity and mortality of pneumococcal bacteremia in patients with cancer, we reviewed the 36 case records of patients with one or more blood cultures positive for pneumococci, observed over a 6-year period at the Institut Jules Bordet. The most frequent underlying neoplasms were lung cancer (25%), chronic lymphocytic leukemia and multiple myeloma (25%). In 80% of the patients, the respiratory tract was the source of the infection. A bacteriological clue for pneumococcal infection was available in 21 patients at the onset of bacteremia; pneumococci were seen on Gram-stained smears in 52% and grown in culture in 76% of all the patients. Most patients (33/36) received adequate empirical treatment as soon as the infection was clinically suspected. Nevertheless, the overall mortality during the week following the infection was 42%; 10 of these deaths could be directly attributed to the pneumococcal infection and occurred during the first 3 days after its onset. Among these 10 patients, 8 had been appropriately treated.     

Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases

Background

To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases.

Methods

Between 2000 and 2013, 737 patients underwent upfront SRS for brain metastases. Patients were stratified by whether or not they received targeted agents with SRS. 167 (23%) received targeted agents compared to 570 (77%) that received other available treatment options. Time to event data were summarized using Kaplan-Meier plots, and the log rank test was used to determine statistical differences between groups.

Results

Patients who received SRS with targeted agents vs those that did not had improved overall survival (65% vs. 30% at 12 months, p < 0.0001), improved freedom from local failure (94% vs 90% at 12 months, p = 0.06), improved distant failure-free survival (32% vs. 18% at 12 months, p = 0.0001) and improved freedom from whole brain radiation (88% vs. 77% at 12 months, p = 0.03). Improvement in freedom from local failure was driven by improvements seen in breast cancer (100% vs 92% at 12 months, p < 0.01), and renal cell cancer (100% vs 88%, p = 0.04). Multivariate analysis revealed that use of targeted agents improved all cause mortality (HR = 0.6, p < 0.0001).

Conclusions

Targeted agent use with SRS appears to improve survival and intracranial outcomes.     

Effect of short-term carbapenem restriction on the incidence of non-pseudomonal multi-drug resistant Gram-negative bacilli in an intensive care unit

We conducted a two-phase retrospective study to investigate the impact of a short-term carbapenem restriction on the incidence of non-pseudomonal multidrug-resistant (MDR) Gram-negative bacilli in our intensive care unit (ICU). The first phase of the study (before carbapenem restriction) was conducted between May and July 2016, and the second phase (implementation of carbapenem restriction) between September and November 2016. The incidence of all non-pseudomonal MDR Gram-negative bacilli (extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae and MDR Acinetobacter baumannii) decreased significantly after carbapenem restriction. Patients positive for non-pseudomonal MDR Gram-negative bacilli before and after carbapenem restriction were comparable in terms of age, weight, Acute Physiology and Chronic Health Evaluation IV score, central venous catheter placement, and vasopressor use. This report suggests that short-term carbapenem restriction for 3?months may be an effective strategy for reducing the incidence of non-pseudomonal MDR Gram-negative bacilli.     

Management of the critically ill patient with severe sepsis

Sepsis is a common cause of morbidity and mortality among the critically ill patient population. However, no anti-sepsis therapy has yet been found to be effective and treatment is thus largely supportive. Adequate fluid resuscitation must be accompanied by effective ventilation, and adrenergic agents may be needed to restore perfusion pressure and improve myocardial function. Enteral nutritional support with specialized nutrients has beneficial effects on morbidity, and should be started early. Further research will allow better definition of the septic patient according to immune status and enable more effective targeting of future anti-sepsis treatments.     

Impact of intravenous administration of voriconazole in critically ill patients with impaired renal function

The administration of voriconazole by the intravenous (i.v.) route in patients with moderate or severe renal failure is limited because of potential toxic effects of the accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium. This study aimed to assess the impact of intravenous voriconazole administration on renal and liver function in critically ill patients with impaired renal function treated with this antifungal drug. The study population consisted of a retrospective cohort of patients admitted to medical-surgical intensive care units (ICUs) who were treated with i.v. voriconazole for more than 3 days. Patients with impaired renal function were those with serum creatinine concentration >1.5 mg/dL, creatinine clearance <50 mL/min, or under any extrarenal depuration procedure. Renal damage was defined as an increase of at least = 2 times initial serum creatinine level or starting of an extrarenal depuration procedure during voriconazole therapy. Liver damage was defined as an increase of = 4 times the initial serum concentration of liver enzymes, or = 2 times in patients with previous impaired liver function. A total of 69 patients was included in the study of which 26 (37.7%) had impaired renal function at the beginning of voriconazole treatment (serum creatinine >2.5 mg/dL in 10 patients). Mean (SD) duration of voriconazole treatment was 13.0 (9.5) days in patients with normal renal function and 11.2 (6.3) days in those with altered renal function. Renal damage during voriconazole therapy occurred in 13 (30.2%) patients with initial normal renal function and in 4 (15.4%) in patients with impaired renal function (P = 0.257). Liver damage during treatment with voriconazole was observed in 12 (27.9%) patients with normal initial renal function and in 3 (11.5%) patients with impaired renal function (P = 0.281). Renal failure developing during voriconazole treatment was associated with a significantly higher mortality rate (82.4% vs. 44.%, P = 0.01), except in the subgroup of patients with altered renal function before starting i.v. voriconazole (60% size=1>vs. 75%, P = 0.385). The use of i.v. voriconazole in ICU patients with pretreatment impaired renal function was not associated with renal or liver damage nor with an increase in ICU mortality.     

Impact of baseline visceral fat accumulation on prognosis in patients with metastatic renal cell carcinoma treated with systemic therapy

Medical Oncology - Liver thermal ablation is an alternative treatment for hepatocellular carcinoma (HCC) and secondary liver malignancies. Microwave ablation (MWA) produces large ablation zones...     

系统护理干预对转移性脊柱肿瘤患者手术切除治疗后的影响

目的探讨系统护理干预对转移性脊柱肿瘤患者手术切除治疗后压疮和焦虑抑郁情绪的影响。方法选取2014年1月至2016年4月间西南医科大学附属医院收治行手术切除治疗的120例转移性脊柱肿瘤患者,采用随机数表法分为观察组与对照组,每组60例。观察组患者在压疮常规护理的基础上予以系统干预护理,对照组患者予以压疮常规护理。比较两组患者护理干预前后焦虑与抑郁改善情况及压疮发生情况。结果干预前,两组患者焦虑和抑郁评分比较,差异均无统计学意义(均P>0.05)。干预后,两组患者焦虑和抑郁情况均有好转,且观察组患者好转情况明显优于对照组,差异均有统计学意义(均P<0.05)。干预后,观察组患者压疮发生率为3.3%,明显少于对照组的23.3%,差异有统计学意义(P<0.05)。结论系统护理干预能改善转移性脊柱肿瘤患者手术切除后的抑郁和焦虑情况,降低压疮发生率,提高生活质量。     

Frequency of occurrence and antimicrobial susceptibility of Gram-negative bacteremia isolates in patients with urinary tract infection: results from United States and European hospitals (2009–2011)

Abstract

We evaluated the frequency of occurrence and antimicrobial susceptibility patterns of Gram-negative bacteria isolated from bacteremic patients with UTI from European (EU) and United States (USA) hospitals during a 3-year period (2009–2011). Susceptibility testing was performed by the reference broth microdilution method on 2071 Gram-negative bacilli. The most frequently isolated pathogens were Escherichia coli (63·3/71·3% in USA/EU), Klebsiella spp. (16·7/11·2%) and Proteus mirabilis (6·4/5·0%). Escherichia coli susceptibility rates were generally similar in the USA and EU, with extended-spectrum beta-lactamase (ESBL)-phenotype rates at 8·1% in both regions. Among Klebsiella spp., ESBL rates varied from 11·4/17·1% in 2009 to 16·1/40·4% in 2011 in USA/EU, and susceptibility rates were generally lower in EU compared to the USA. Pseudomonas aeruginosa exhibited lower susceptibility rates to ceftazidime, meropenem and piperacillin/tazobactam in EU (78·4, 78·4 and 76·5%, respectively) compared to USA (91·2, 88·2 and 91·2%, respectively). In summary, very few antimicrobials provided satisfactory coverage (>90%) when tested against Klebsiella spp. and P. aeruginosa isolates in EU.     

Recurrent Candida sepsis with prolonged respiratory failure and severe liver dysfunction

Systemic mycoses, especially pulmonary diseases and septicemia are observed increasingly at intensive care units. Essential risk factors for development of candidosis are the expanded use of antibiotics and immunocompromised patients, caused either as a result of a severe underlying disease or iatrogenically induced after organ transplantation. Candida albicans is the most frequent pathogen in microbiological findings. Blood cultures are only positive in massive fungemia. We report a 50-year-old patient with recurrent Candida-septicemia: rupture of the distal esophagus after dilatation because of cardiac achalasia with mediastinal emphysema and mediastinitis. Severe acute respiratory distress syndrome after aspiration with septic shock and acute renal failure at the beginning. Long-term mechanical ventilation, continuous renal replacement therapy and multifarious antibiotic therapy. Early microbiological samples of several positive blood cultures and bronchoalveolar lavages revealed the presence of Candida albicans. In the further clinical course, detection of Pseudomonas species in bronchoalveolar lavages and Staphylococci as well as Enterococci in a number of positive blood cultures. Later on development of a severe liver dysfunction with test results that showed an intrahepatic cholestasis. Because of coagulation failure commencement of artificial liver support with the MARS-system (molecule adsorbent recirculating system). Decrease of high bilirubin levels was accompanied by improvement of clinical condition of the patient. In the following course, repeated severe systemic infections with phases of septicemia or rather septic shock and detection of Candida in several positive blood cultures and bronchoalveolar lavages. In each case increasing bilirubin levels with signs of intrahepatic cholestasis and each time improvement with antimycotic therapy (voriconazol, caspofungin and fluconazol). The patient showed more and more signs of immunodeficiency in the sequel. The clinical appearance of candidosis is manifold. Systemic Candida infections are frequent in patients with immunodeficiency. A recurrent Candida septicemia with prolonged respiratory failure and severe liver dysfunction in form of cholestatic hepatosis, that improved several times with antimycotic therapy in combination with evidence based intensive care measures and artificial organ support is a comparatively rare event.     

Impact of surgery,radiation and systemic therapy on the outcomes of patients with dendritic cell and histiocytic sarcomas

BackgroundNeoplasms of histiocytic and dendritic cell origin, including follicular dendritic cell sarcoma (FDCS), histiocytic sarcoma (HS) and interdigitating dendritic cell sarcoma (IDCS), are extremely rare, and data on their natural history and treatment outcomes are sparse. We evaluated the impact of surgery, radiation and systemic therapies on overall survival (OS).MethodsWe conducted a retrospective chart review of patients with FDCS, IDCS and HS treated at Memorial Sloan Kettering Cancer Center between 1995 and 2014.ResultsWe identified 31, 15 and 7 patients with FDCS, HS and IDCS, respectively.Median age was 48.7, 42.3 and 58.8 years for FDCS, HS and IDCS, respectively. Only a slight disparity in gender distribution existed for FDCS and HS; however, IDCS predominantly affected males (6:1). The most common sites of presentation were abdomen and pelvis (42%), extremities (33%) and head and neck (57%) for FDCS, HS and IDCS, respectively. At diagnosis, 74%, 40% and 86% of patients presented with localised disease in FDCS, HS and IDCS, respectively. Patients with localised disease had significantly improved OS than those with metastatic disease in FDCS (P = 0.04) and IDCS (P = 0.014) but not in HS (P = 0.95). In FDCS and HS, adjuvant or neo-adjuvant therapy was not associated with improved OS compared with observation. In IDCS, surgery alone provided a 5-year overall survival rate of 71%.ConclusionsAdjuvant or neo-adjuvant treatment in FDCS and HS did not affect OS. Patients with IDCS had an excellent outcome with surgery. In the metastatic setting, chemotherapy and small molecule inhibitors may provide benefit.     

免疫营养治疗对肿瘤患者脓毒血症的疗效观察

目的 探讨免疫增强型复合肠内营养制剂对脓毒血症肿瘤患者的临床疗效.方法 选择2018年6月至2020年7月重庆市大足区人民医院重症监护室收治的符合入选标准的合并脓毒血症肿瘤患者,随机分为试验组和对照组,各30例.对照组给予常规营养治疗,试验组在对照组的基础上加用富含免疫增强型复合肠内营养制剂治疗.并监测比较两组患者在3...     

Impact of highly active antiretroviral therapy in the treatment of HIV-infected patients with systemic non-Hodgkin's lymphoma

Twenty cases of systemic non-Hodgkin's lymphoma (NHL) in HIV-infected patients were reviewed over a 10-year-period, divided into Group A, including 13 NHL cases treated before the highly active antiretroviral therapy (HAART) era, and Group B, including 7 patients who received HAART. A Kaplan-Meier survival curve was performed and log-rank was applied to assess statistical differences between the groups. In group A, the median CD4 count was 36 cells/mm 3 . No complete remission was found. In group B, the median CD4 count was 137 cells/mm 3 . Four patients (57.0%) are still alive and in complete remission. Group A had a median survival of 5 months and group B 31 months (p=0.0032). Our results are in agreement with recent reports in that a higher CD4 count and better immune status achieved with HAART is predictive of a better outcome. We found that HAART in combination with chemotherapy improves overall survival of NHL patients without increasing adverse effects.     

Impact of resection and systemic therapy on the survival of patients with brain metastasis of metastatic renal cell carcinoma

Patients with brain metastasis (BM) from renal cell carcinoma (RCC) are associated with poor prognosis. Between 1990 and 2015, data of consecutive RCC patients with BM were retrospectively analyzed from a urologic oncologic database. The treatment outcome was evaluated by overall survival (OS), which was defined as interval from initial diagnosis of BM to death or last follow-up. Statistical analyses of clinical and pathological variables were performed using Cox regression and the Kaplan–Meier method. A total of 116 RCC patients with BM were included. Median time from initial diagnosis of RCC to BM was 15.8 months (95?% CI 11.6–20.0). Median OS after diagnosis of brain metastases of the whole cohort was 5.8 months (95?% CI 4.3–7.2). On multivariate Cox regression analysis, age and histology of non-clear cell RCC were associated with poorer outcome, while targeted therapy (n?=?26) (OS 9.9 months, 95?% CI 3.3–16.5) and BM resection (n?=?33) (OS 24.7 months, 95?% CI 4–40) were associated with better survival. Furthermore, patients who underwent both targeted therapy and BM resection (n?=?5) had the best outcome with median OS of 52.4 months. In conclusion, BM from RCC is associated with a poor oncological outcome. Furthermore, age and histology of non-clear cell RCC are risk factors for poor prognosis. Patients with resectable BM may comprise a better prognostic group. Here, a better OS for resected than unresected patients was observed, which warrants BM resection. A combined modality approach of resection and targeted therapy appears to further improve the outcome of these patients while additional radiation seems to add no benefit.     

Health-care associated bacteremia in geriatric cancer patients with febrile neutropenia

ObjectiveThe aim of this study was to determine the epidemiology, clinical manifestations, and outcome of health-care associated bacteremia in geriatric cancer patients with febrile neutropenia.Materials and MethodsWe retrospectively evaluated cancer patients with febrile neutropenia aged ≥ 60 years with culture proven health-care associated bacteremia between January 2005 and December 2011. The date of the first positive blood culture was regarded as the date of bacteremia onset. Primary outcome was the infection related mortality, defined as the death within 14 days of bacteremia onset.ResultsThe two most common pathogens responsible for bacteremia were Staphylococcus epidermidis (36.1%) and Escherichia coli (31.5%), with high rates of methicillin resistance and extended-spectrum β-lactamase (ESBL) production, respectively. There were no statistically significant differences in infection related mortality rate according to the type of malignancy (p = 0.776). By the univariate analysis, factors associated with 14 day mortality among febrile neutropenic episodes were prolonged neutropenia (p = 0.024), persistent fever (p = 0.001), hospitalization in ICU (p < 0.001) and the initial clinical presentations including respiratory failure (p < 0.001), hepatic failure (p = 0.013), hematological failure (p < 0.001), neurological failure (p < 0.001), severe sepsis (p < 0.001), and septic shock (p = 0.036). Multivariate analysis showed that persistent fever was an independent factor associated with infection related mortality (odds ratio, 18.0; 95% confidence interval, 5.2–62.6; p < 0.001).ConclusionsThe only independent risk factor for mortality was persistent fever. Although the most frequently isolated pathogens were S. epidermidis and E. coli, high rates of methicillin resistance and ESBL production were found respectively.