Burkholderia gladioli: five year experience in a cystic fibrosis and lung transplantation center.

BACKGROUND: The impact of infection with Burkholderia gladioli in cystic fibrosis, other chronic airway diseases and immunosuppressed patients is unknown. METHODS: A six-year retrospective review of all patients with B. gladioli infection was performed in a tertiary referral center with cystic fibrosis and lung transplantation programs. In addition, a targeted survey of all 251 lung transplant recipients was performed. Available B. gladioli isolates were analyzed via pulsed field gel electrophoresis. RESULTS: Thirty-five patients were culture positive for B. gladioli, including 33 CF patients. No bacteremia was identified. Isolates were available in 18 patients and all were genetically distinct. Two-thirds of these isolates were susceptible to usual anti-pseudomonal antibiotics. After acquisition, only 40% of CF patients were chronically infected (> or =2 positive cultures separated by at least 6 months). Chronic infection was associated with resistance to > or =2 antibiotic groups on initial culture and failure of eradication after antibiotic therapy. The impact of acquisition of B. gladioli infection in chronic infection was variable. Three CF patients with chronic infection underwent lung transplantation. One post-transplant patient developed a B. gladioli mediastinal abscess, which was treated successfully. CONCLUSIONS: The majority of patients' culture positive for B. gladioli at our center have CF. B. gladioli infection is often transient and is compatible with satisfactory post-lung transplantation outcomes.     

Arterial line filtration during cardiopulmonary bypass. Neurologic, neuropsychologic, and hematologic studies

One hundred patients who underwent elective cardiac operations were randomized into two groups. Group 1 had a 20 micron nylon screen filter in the arterial line. In Group 2 no filter was used in the arterial line. Neurologic and neuropsychologic examination of the patients was performed with seven psychometric tests of the Wechsler Memory Scale and the Wechsler Adult Intelligence Scale. These tests were conducted before and a mean of 10 days after the operation. Platelet counts and hemoglobin and total protein levels were measured at the onset and at the end of cardiopulmonary bypass. Two patients died during their hospital stay. Neurologic damage with focal signs was found in the postoperative examination in six patients (three in each group). Twenty-eight patients (28.5%) exhibited signs of mild cerebral dysfunction as assessed by the presence of archaic (primitive) reflexes. Fifteen were in Group 1 and 13 in Group 2 (no significant difference). Sixty patients (61%) had decrements greater than one standard deviation in at least one of the three tests that showed most decreased postoperative scores. There were 32 in Group 1 and 28 in Group 2 (no significant difference). When each test was analyzed individually, there were no significant differences between the two groups. Platelet counts decreased, during cardiopulmonary bypass, a mean of 33% in Group 1 and 34.5% in Group 2 (no significant difference). Both hemoglobin and total protein levels remained virtually unchanged. These results indicate that the addition of a small-pore filter in the arterial line does not prevent the neurologic and neuropsychologic disturbances frequently encountered after cardiopulmonary bypass. The filter itself does not appear to have a direct effect on the blood components. Routine use of an arterial line filter remains questionable.     

Bilateral Hematogenous Pseudomonas aeruginosa Endophthalmitis After Lung Transplantation

Pseudomonas aeruginosa commonly colonizes the airways of patients with cystic fibrosis (CF). However, the occurrence of bacteremia with metastatic infection to the eye causing endogenous endophthalmitis is very rare. In the setting of lung transplantation, the significance of P. aeruginosa bacteremia in patients with CF whose airways are colonized before transplantation is unknown. We report a case of bilateral P. aeruginosa endogenous endophthalmitis in a patient with CF after lung transplant without documented bacteremia. The patient presented with acute eye symptoms in the presence of a left atrial thrombus and the disease followed a rapidly progressive course requiring aggressive medical-surgical treatment. Typically P. aeruginosa endophthalmitis has been associated with a poor visual prognosis. However, with combined medical-surgical management this patient retained useful vision in one eye without having retinal detachment or requiring enucleation. Endogenous endophthalmitis should be considered in the differential diagnosis of ocular complaints in patients with CF after lung transplant.     

Protocols for the dosimetry of high-energy photon and electron beams: a comparison of the IAEA TRS-398 and previous international codes of practice. International Atomic Energy Agency

A new international Code of Practice for radiotherapy dosimetry co-sponsored by several international organizations has been published by the IAEA, TRS-398. It is based on standards of absorbed dose to water, whereas previous protocols (TRS-381 and TRS-277) were based on air kerma standards. To estimate the changes in beam calibration caused by the introduction of TRS-398, a detailed experimental comparison of the dose determination in reference conditions in high-energy photon and electron beams has been made using the different IAEA protocols. A summary of the formulation and reference conditions in the various Codes of Practice, as well as of their basic data, is presented first. Accurate measurements have been made in 25 photon and electron beams from 10 clinical accelerators using 12 different cylindrical and plane-parallel chambers, and dose ratios under different conditions of TRS-398 to the other protocols determined. A strict step-by-step checklist was followed by the two participating clinical institutions to ascertain that the resulting calculations agreed within tenths of a per cent. The maximum differences found between TRS-398 and the previous Codes of Practice TRS-277 (2nd edn) and TRS-381 are of the order of 1.5-2.0%. TRS-398 yields absorbed doses larger than the previous protocols, around 1.0% for photons (TRS-277) and for electrons (TRS-381 and TRS-277) when plane-parallel chambers are cross-calibrated. For the Markus chamber, results show a very large variation, although a fortuitous cancellation of the old stopping powers with the ND,w/NK ratios makes the overall discrepancy between TRS-398 and TRS-277 in this case smaller than for well-guarded plane-parallel chambers. Chambers of the Roos-type with a 60Co ND,w calibration yield the maximum discrepancy in absorbed dose, which varies between 1.0% and 1.5% for TRS-381 and between 1.5% and 2.0% for TRS-277. Photon beam calibrations using directly measured or calculated TPR20,10 from a percentage dose data at SSD = 100 cm were found to be indistinguishable. Considering that approximately 0.8% of the differences between TRS-398 and the NK-based protocols are caused by the change to the new type of standards, the remaining difference in absolute dose is due either to a close similarity in basic data or to a fortuitous cancellation of the discrepancies in data and type of chamber calibration. It is emphasized that the NK-ND,air and ND,w formalisms have very similar uncertainty when the same criteria are used for both procedures. Arguments are provided in support of the recommendation for a change in reference dosimetry based on standards of absorbed dose to water.     

Direct infant UV light exposure is associated with eczema and immune development

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Surgical management of aortic coarctation associated with ruptured cerebral artery aneurysm

We report two patients with coarctation of the aorta who were admitted to the hospital with ruptured cerebral artery aneurysms. In both patients, we surgically treated the coarctation and later repaired the intracranial lesion. One patient, a 34-year-old woman, is alive and well after 3 years; whereas, the other, a 19-year-old man, did not survive. We discuss the sequence for surgery, which continues to be subjected to debate.     

Carboplatin plus gemcitabine in patients with inoperable or metastatic pancreatic cancer: a phase II multicenter study by the Hellenic Cooperative Oncology Group.

BACKGROUND: In the present phase II multicenter study, we assessed the efficacy and tolerability of the combination of gemcitabine and carboplatin in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated, locally advanced or metastatic pancreatic cancer were treated with gemcitabine 800 mg/m(2) on days 1 and 8 and carboplatin at an AUC of 4 on day 8 of a 3-week cycle, for a total of six cycles. Primary end points were response rate and clinical benefit; secondary end points were, survival, time to progression (TTP) and toxicity. RESULTS: A total of 50 patients were enrolled in the study, 47 of whom were eligible for treatment. The median age was 63 years (range 34-76) and the median Karnofsky performance status (PS) was 80%. Patients received a median of six cycles (range 1-11). Among 35 patients evaluable for response, eight (17%) achieved partial response; 15 (32%) and 12 (25%) patients had stable and progressive disease, respectively. The median overall survival was 7.4 months; the median TTP was 4.4 months and the 1-year survival was 28%. The observed clinical benefit response was remarkable. After the second cycle of chemotherapy, 21 of 31 (68%) patients experienced pain improvement and reduced analgesic consumption. At the same time, 35% and 56% of our patients significantly improved their Karnofsky PS and weight, respectively. Overall, the treatment was well tolerated. The most common grade 3-4 toxicities were hematological, including 8% anemia, 6% neutropenia and 13% thrombocytopenia. CONCLUSIONS: The combination of gemcitabine plus carboplatin is a moderately active treatment for patients with locally advanced and metastatic pancreatic cancer. This regimen has an acceptable toxicity profile and provides a significant clinical benefit, and hence warrants further investigation.     

Irinotecan or oxaliplatin combined with leucovorin and 5-fluorouracil as first-line treatment in advanced colorectal cancer: a multicenter, randomized, phase II study.

BACKGROUND: Irinotecan (IRI) and oxaliplatin (OXA) are effective in the treatment of colorectal cancer. Previously untreated patients with advanced colorectal carcinoma (CRC) were randomly assigned to receive IRI plus leucovorin (LV)/5-fluorouracil (5-FU), or OXA plus LV/5-FU in order to compare the response rates, time-to-tumor progression, overall survival rates, and toxicity profiles of these two agents. MATERIALS AND METHODS: From January 1999 to February 2002, 295 patients were randomized to receive either IRI/LV/5-FU or OXA/LV/5-FU. The treatment schedules consisted of weekly IRI 70 mg/m(2) or OXA 45 mg/m(2) plus LV 200 mg/m(2) followed immediately by intravenous bolus 5-FU 450 mg/m(2) for 6 weeks, followed by a 2-week rest period. Treatment was continued for up to four cycles or until disease progression, unacceptable toxicity or patient refusal. RESULTS: There were no significant differences between the study arms in the overall response rate (33% with IRI/LV/5-FU versus 32% with OXA/LV/5-FU based on responses demonstrated on a single evaluation; 23% with IRI/LV/5-FU versus 22.3% with OXA/LV/5-FU based on responses confirmed according to WHO criteria) median time to progression (8.9 versus 7.6 months), and median overall survival (17.6 versus 17.4 months). Toxicity profiles (grades 3 and 4) were similar in the IRI and OXA arms (diarrhea 12.3% and 9.8%, neutropenia 8.2% and 4.9%, and febrile neutropenia 1.4% and 1.4%, respectively), with the exception of grade 3 sensory neuropathy, which almost exclusively occurred in the OXA arm (0% versus 5.6%; P=0.003, Fisher's exact test). CONCLUSION: The IRI/LV/5-FU and OXA/LV/5-FU regimens demonstrated equally substantial efficacies and manageable toxicity profiles in the first-line treatment of patients with advanced CRC. However, IRI/LV/5-FU may be the preferable regimen to avoid significant neurotoxicity associated with OXA-LV/5-FU.     

Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors.

PURPOSE: Osteonecrosis of the jaw (ONJ) has been associated recently with the use of pamidronate and zoledronic acid. We studied the incidence, characteristics, and risk factors for the development of ONJ among patients treated with bisphosphonates for bone metastases. PATIENTS AND METHODS: ONJ was assessed prospectively since July 2003. The first bisphosphonate treatment among patients with ONJ was administered in 1997. Two hundred fifty-two patients who received bisphosphonates since January 1997 were included in this analysis. RESULTS: Seventeen patients (6.7%) developed ONJ: 11 of 111 (9.9%) with multiple myeloma, two of 70 (2.9%) with breast cancer, three of 46 (6.5%) with prostate cancer, and one of 25 (4%) with other neoplasms (P = .289). The median number of treatment cycles and time of exposure to bisphosphonates were 35 infusions and 39.3 months for patients with ONJ compared with 15 infusions (P < .001) and 19 months (P = .001), respectively, for patients with no ONJ. The incidence of ONJ increased with time to exposure from 1.5% among patients treated for 4 to 12 months to 7.7% for treatment of 37 to 48 months. The cumulative hazard was significantly higher with zoledronic acid compared with pamidronate alone or pamidronate and zoledronic acid sequentially (P < .001). All but two patients with ONJ had a history of dental procedures within the last year or use of dentures. CONCLUSION: The use of bisphosphonates seems to be associated with the development of ONJ. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor.     

Breast cancer stem cells: Multiple capacities in tumor metastasis

Breast cancer is the leading cause of cancer death among women worldwide. Accumulating evidence indicates that the local recurrent and/or distant metastatic tumors, the major causes of lethality in the clinic, are related to the aggressive phenotype of a small fraction of cancer cells loosely termed as cancer stem cells (CSCs), tumor initiating cells (TICs), or cancer metastasis-initiating cells (CMICs). Breast cancer stem cells (BCSCs) are shown to exhibit unique growth abilities including self-renewal, differentiation potential, and resistance to most anti-cancer agents including chemo- and/or radiotherapy, all of which are believed to contribute to the development and overall aggressiveness of the recurrent or metastatic lesions. It is in the urgent need not only to further define the nature of heterogeneity in each tumor but also to characterize the precise mechanisms governing tumor–host cross-talk which is assumed to be initiated by BCSCs. In this review, we will focus on recently identified key factors, including the BCSCs among circulating tumor cells, interaction of BCSCs with the host, epithelial mesenchymal transition (EMT), tumor microenvironment, the intrinsic resistance due to HER2 expression, potential biomarkers of BCSCs and cancer cell immune signaling. We believe that new evidence coming from both bench and clinical research will help to develop more effective approaches to control or significantly reduce the aggressiveness of metastatic tumors.