Cytomegalovirus infection in intensive care unit patients with hematological malignancies: Characteristics and clinical outcomes.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with poor outcome in ICU patients. However, data on immunocompromised patients are scarce. This study aims to describe characteristics and outcomes of critically ill hematological patients and CMV infection. CMV disease characteristics and relationship between CMV viral load, CMV disease, coinfections by other pathogens and outcomes are described. METHODS: Retrospective single center study (Jan 2010-Dec 2017). Adult patients, admitted to the ICU, having underlying hematological malignancy and CMV infection were included. Results are reported as median (interquartile) or n (%). Factors associated with hospital mortality or CMV disease were analysed using logistic regression. RESULTS: 178 patients were included (median age 55y [42-64], 69.1% male). Hospital mortality was 53% (n = 95). Median viral load was 2.7 Log [2.3-3.5]. CMV disease occurred in 44 (24.7%) patients. Coinfections concerned 159 patients (89.3%). After adjustment for confounders, need for vasopressors (OR 2.53; 95%CI 1.11-5.97) and viral load (OR 1.88 per Log; 95%CI 1.29-2.85) were associated with hospital mortality. However, neither CMV disease nor treatment were associated with outcomes. Allogeneic stem cell transplantation (OR 2.55; 95%CI 1.05-6.16), mechanical ventilation (OR 4.11; OR 1.77-10.54) and viral load (OR 1.77 per Log; 95%CI 1.23-2.61) were independently associated with CMV disease. Coinfections were not associated with CMV disease or hospital mortality. CONCLUSION: In critically-ill hematological patients, CMV viral load is independently associated with hospital mortality. Conversely, neither CMV disease nor treatment was associated with outcome suggesting viral load to be a surrogate for immune status rather than a cause of poor outcome.

Augmented Reality Guided Laparoscopic Surgery of the Uterus.

A major research area in Computer Assisted Intervention (CAI) is to aid laparoscopic surgery teams with Augmented Reality (AR) guidance. This involves registering data from other modalities such as MR and fusing it with the laparoscopic video in real-time, to reveal the location of hidden critical structures. We present the first system for AR guided laparoscopic surgery of the uterus. This works with pre-operative MR or CT data and monocular laparoscopes, without requiring any additional interventional hardware such as optical trackers. We present novel and robust solutions to two main sub-problems: the initial registration, which is solved using a short exploratory video, and update registration, which is solved with real-time tracking-by-detection. These problems are challenging for the uterus because it is a weakly-textured, highly mobile organ that moves independently of surrounding structures. In the broader context, our system is the first that has successfully performed markerless real-time registration and AR of a mobile human organ with monocular laparoscopes in the OR.

Impact of uncontrolled freezing and long-term storage of peripheral blood stem cells at - 80 °C on haematopoietic recovery after autologous transplantation. Report from two centres.

Controlled-rate freezing and storage in vapour phase nitrogen are used by most transplantation teams for the cryopreservation and storage of peripheral blood haematopoietic stem cells (PBSC). In this study, we analysed 666 autologous PBSC transplants after uncontrolled freezing and storage of PBSC at -80 °C. Statistical analysis showed that neutrophil recovery was associated with both the infused CD34(+) cell dose (P=0.01) and the post transplantation use of growth factors (P<0.001) and that platelet recovery was associated with the infused CD34(+) cell dose (P<0.001) and with the diagnosis (P=0.02). We analysed three groups according to the duration of the cryopreservation period (less than 6 months, between 6 and 12 months or more than 1 year). Haematopoietic recovery was not found to be adversely affected by longer storage at -80 °C. The haematopoietic recoveries of 50 pairs of sequential transplantations from the same PBSC mobilization were analysed. Despite prolonged cryopreservation, there were no statistically significant differences in neutrophil (P=0.09) or platelet (P=0.22) recovery in the second compared with the first transplant. In conclusion, the long-term storage of PBSC at -80 °C after uncontrolled-rate freezing is an easy and comparatively inexpensive cryopreservation method that leads to successful haematopoietic recovery even after prolonged storage.

Assembly of molecular nanomagnets into nanogap electrodes by dielectrophoresis.

We investigate the assembly of Prussian blue and Cs-Co-Cr Prussian blue analogue molecular nanomagnets into nano-patterned electrodes. Pd or Au gaps - 7-50 nm were fabricated on a SiO2/Si substrate using standard electron beam lithography and lift-off. Nanomagnets were positioned between the gaps via AC dielectrophoresis (DEP). At room temperature, the Cs-Co-Cr Prussian blue analogue nanoparticles exhibited negligible current whereas junction with Prussian blue nanoparticles exhibited - 30 pA at - 1 V.

[Monitoring of antibiotic resistance of gram negative anaerobes]. / Surveillance de la résistance aux antibiotiques des anaérobies stricts à Gram négatif.

MATERIAL AND METHOD: Using an agar reference method (Norma M11-A5, National Committee for Clinical and Laboratory Standards) the minimal inhibitory concentrations of nine antibiotics were determined for 376 anaerobic strains. The following strains were investigated: 254 Bacteroides fragilis group (including 143 B. fragilis), 122 other gram-negative anaerobes (Bacteroides spp., Prevotella, Fusobacterium, Porphyromonas, Suterella, Desulfomonas, Veillonella). RESULTS: In the B. fragilis group resistance rates were: coamoxyclav 2.8%, ticarcillin 27.5%, ticarcillin-clavulanic acid 1.9%, piperacillin-tazobactam 1.9%, cefoxitin 6.2%, imipenem 0.8%, clindamycin 28.3%, respectively. Based on previous studies, resistance to imipenem remained low in 2003 and was only observed for B. fragilis. Resistance to clindamycin was maintained around 25%. No metronidazole resistance was observed, but decreased susceptibility was found for B. fragilis, B. merdae and Prevotella, as in 4.3% of gram-negative anaerobes. DISCUSSION: This study confirms the high resistance rate of gram-negative anaerobes to clindamycin, the efficient activity of imipenem, beta-lactam/beta-lactamase inhibitor combinations and metronidazole. However, reduced metronidazole susceptibility seems to be increasing.

Transport spectroscopy of single Pt impurities in silicon using Schottky barrier MOSFETs.

We investigate low temperature electron transport in silicon Schottky barrier metal-oxide-semiconductor field-effect transistors (MOSFETs), which consist of PtSi metallic source/drain electrodes. Measurements are made on approximately 23 inversion layers and resonances attributed to single impurities close to the metal/semiconductor interface are observed. We ascribe these impurities to Pt atoms that have diffused into the semiconductor channel from the contacts.

Antimicrobial susceptibilities and clinical sources of Dialister species.

Seventy-four strains representing the four species of the genus Dialister were isolated from various clinical samples. Dialister pneumosintes and Dialister micraerophilus were the two mainly encountered species. Fifty-five isolates were tested against 14 antimicrobial agents. Decreased susceptibilities to piperacillin, metronidazole, macrolides, fluoroquinolones, and rifampin were demonstrated. The clinical impact of these decreased susceptibilities remains to be investigated but should prompt microbiologists to perform antimicrobial susceptibility testing for clinically important Dialister spp.

Observation of the linear stark effect in a single acceptor in Si.

The Stark splitting of a single fourfold degenerate impurity located within the built-in potential of a metal-semiconductor contact is investigated using low temperature transport measurements. A model is developed and used to analyze transport as a function of temperature, bias voltage, and magnetic field. Our data is consistent with a boron impurity. We report g factors of g_{1/2}=1.14 and g_{3/2}=1.72 and a linear Stark splitting 2Delta of 0.1 meV.

In vitro activity against anaerobes of retapamulin, a new topical antibiotic for treatment of skin infections.

OBJECTIVES: Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections. The aim of this study was to determine the antimicrobial activity of retapamulin by determining the minimal inhibitory concentration (MIC) values of this new drug and comparators against a wide range of anaerobic bacteria of human origin. METHODS: The in vitro activity of retapamulin and six comparators (amoxicillin, amoxicillin/clavulanic acid, ceftriaxone, imipenem, clindamycin and metronidazole) was evaluated against 232 anaerobic clinical isolates. MICs were determined by the CLSI reference agar dilution method (M11-A6). RESULTS: Ceftriaxone, clindamycin and amoxicillin/clavulanic acid resistance rates were 54%, 42% and 9.6%, respectively, within the Bacteroides fragilis group. Despite high resistance rates to various antibiotics, retapamulin inhibited 37/52 (71%) strains of the B. fragilis group and 85/87 (98%) of the other Gram-negative bacilli at a concentration of 2 mg/L or less. All the investigated strains of Clostridium perfringens were inhibited by 1 mg/L retapamulin. Three strains of C. difficile and one strain of C. clostridioforme demonstrated decreased susceptibility to retapamulin. Based on inhibitory concentrations, retapamulin was more active than clindamycin, metronidazole and ceftriaxone against Propionibacterium acnes and anaerobic Gram-positive cocci, as all isolates were inhibited by

Evaluation of the in vitro activity of ertapenem and nine other comparator agents against 337 anaerobic bacteria.

Ertapenem activity in vitro was compared with that of nine reference antibiotics against 337 anaerobes by determining minimal inhibition concentrations (MICs). Amongst 246 Gram-negative anaerobes, 4, 8, 3, 4, 7, 2 and 52 strains showed resistance to ertapenem, amoxicillin/clavulanic acid, ticarcillin/clavulanic acid, piperacillin/tazobactam, cefoxitin, imipenem and clindamycin, respectively, and all strains were inhibited by metronidazole. Ertapenem MIC(50) values were 0.5, 0.25, 0.06 and

Pleiotrophin, a candidate gene for poor tumor vasculature and in vivo neuroblastoma sensitivity to irinotecan.

In vivo neuroblastoma (NB) xenograft model, resistant to the DNA-topoisomerase I inhibitor irinotecan (CPT-11), has been established to study resistance mechanisms acquired in a therapeutic setting. Common mechanisms of resistance were not involved in this resistance. Thus, we compared the gene expression profiles of sensitive, resistant, and reverted tumors using cDNA expression arrays. Expression of selected transcripts was confirmed by quantitative real-time PCR. We found that pleiotrophin (PTN), a heparin-binding growth factor, was the only gene significantly affected: PTN gene expression was downregulated in all resistant tumors (8-14-fold) as compared to sensitive tumors, and was increased (2-4-fold) in all reverted tumors as compared to resistant tumors. PTN thus appeared to be a likely candidate gene associated with resistance to CPT-11 in this in vivo model. To investigate the direct implication of PTN in NB, we transfected two NB cell lines with RNA interferences in order to silence PTN. PTN failed to demonstrate implication in resistance to CPT-11 in vitro but could influence sensitivity to CPT-11 exclusively through an in vivo mechanism. Indeed, vasculature was significantly enhanced in resistant NB xenografts compared to sensitive and reverted xenografts, and we suggest that PTN is acting in our resistant in vivo NB model as an angiostatic factor.

No topoisomerase I alteration in a neuroblastoma model with in vivo acquired resistance to irinotecan.

CPT-11 (irinotecan) is a DNA-topoisomerase I inhibitor with preclinical activity against neuroblastoma (NB) xenografts. The aim was to establish in vivo an NB xenograft resistant to CPT-11 in order to study the resistance mechanisms acquired in a therapeutic setting. IGR-NB8 is an immature NB xenograft with MYCN amplification and 1p deletion, which is sensitive to CPT-11. Athymic mice bearing advanced-stage subcutaneous tumours were treated with CPT-11 (27 mg kg(-1) day(-1) x 5) every 21 days (1 cycle) for a maximum of four cycles. After tumour regrowth, a new in vivo passage was performed and the CPT-11 treatment was repeated. After the third passage, a resistant xenograft was obtained (IGRNB8-R). The tumour growth delay (TGD) was reduced from 115 at passage 1 to 40 at passage 4 and no complete or partial regression was observed. After further exposure to the drug, up to 28 passages, the resistant xenograft was definitively established with a TGD from 17 at passage 28. Resistant tumours reverted to sensitive tumours after 15 passages without treatment. IGR-NB8-R remained sensitive to cyclophosphamide and cisplatin and cross-resistance was observed with the topoisomerase I inhibitor topotecan. No quantitative or qualitative topoisomerase I modifications were observed. The level of expression of multidrug resistance 1 (MDR1), MDR-associated protein 1 (MRP1) and, breast cancer resistance protein, three members of the ATP-binding cassette transporter family was not modified over passages. Our results suggest a novel resistance mechanism, probably not involving the mechanisms usually observed in vitro.

A Bacteroides thetaiotamicron porin that could take part in resistance to beta-lactams.

The aim of this study was to investigate porin absence or deficiency in two Bacteroides thetaiotaomicron strains resistant to amoxicillin combined with clavulanic acid. Their outer membrane protein (OMP) extracts and those of two susceptible strains were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and compared to detect differences between the strains. A protein band of interest at around 70 kDa electro-eluted for each strain, was tested in a liposome swelling assay. A decrease in initial absorbency was noted for the two susceptible strains but not for the two resistant strains. The liposome swelling of the two susceptible strains was directly visualized by photon microscopy and then photographed. This suggested a B. thetaiotaomicron porin of around 70 kDa could take part in resistance to beta-lactams.

In vitro activity of gatifloxacin, a new fluoroquinolone, against 204 anaerobes compared to seven other compounds.

The activity of gatifloxacin, a new fluoroquinolone derivative, was compared with the activities of ciprofloxacin, levofloxacin, amoxicillin, amoxicillin-clavulanate, imipenem, clindamycin and metronidazole against 204 anaerobes isolated from clinical specimens, by MIC determination, using the reference agar dilution method. When determining the overall activity against anaerobes, the MIC50/90 (mg/L) values were amoxicillin 16/>64, amoxicillin-clavulanate 0.125/1, imipenem 0.25/0.5, clindamycin 0.5/>256, metronidazole 1/8, ciprofloxacin 2/32, levofloxacin 1/8 and gatifloxacin 0.5/4. The broad in vitro spectrum of gatifloxacin is promising for the treatment of mixed anaerobic infections, especially those of the respiratory tract, ear, sinus, skin and soft tissues, and bite wounds. These data suggest that gatifloxacin may have a clinical role in the treatment of infections in which anaerobic pathogens are involved.

Antibiotic resistance among anaerobic Gram-negative bacilli: lessons from a French multicentric survey.

Temporal changes of antibiotic susceptibilities among anaerobes in France are followed in our laboratory since 1992. For Bacteroides strains, resistance increased from 1992 to 1998 for amoxicillin-clavulanic acid, cefotetan and clindamycin. The present study evaluates the situation in 2000 for 434 Gram-negative anaerobic clinical isolates (obtained from 9 large university hospitals) by testing amoxicillin and ticarcillin alone or combined with clavulanic acid, cefoxitin, cefotetan, imipenem, clindamycin and metronidazole (using the NCCLS-approved method for MIC determination. The main genera tested included Bacteroides (359 strains of the fragilis group), Prevotella (40 strains), Fusobacterium (23 strains) and miscellaneous species (8 strains). Resistance rates within the B. fragilis group were: amoxicillin-clavulanic acid 5.6%, ticarcillin 33%, ticarcillin-clavulanic acid 2%, cefoxitin 13%, cefotetan 44%, clindamycin 33%, imipenem 1% and metronidazole <1%, respectively. Only one strain of B. fragilis was resistant to metronidazole (MIC=64 mg/L); due to the presence of the nimA gene on the chromosome. Resistance to imipenem or metronidazole was only found among the B. fragilis species. These two former drugs excepted, B. fragilis was less resistant to antibiotics than the other species. beta-lactamase production was detected for 357/359 strains of the fragilis group, 26/40 stains of Prevotella and 3/23 strains of Fusobacterium. Dynamic changes of antibacterial resistance are occurring within the B. fragilis group: decreased resistance to amoxicillin-clavulanic acid, ticarcillin-clavulanic acid, imipenem while resistance for cefoxitin, cefotetan, clindamycin continues to increase. Regular antibiotic surveys are needed as a source of information to guide the empirical therapy of anaerobic infections.

Incidence of pheochromocytoma in South Galicia, Spain.

OBJECTIVES: To estimate the incidence of pheochromocytoma in the population of South Galicia (Spain) during the period 1980-1992. DESIGN: A prospective study. SETTING: The General Hospital of Vigo, a tertiary referral centre. SUBJECTS: New cases of pheochromocytoma diagnosed in the population during the years 1980-1992. The average population size was 523,934 inhabitants, (52% female, 48% male). MAIN OUTCOME MEASURES: All data were obtained from the Medical Registry, which ensures virtually complete case ascertainment for diagnosed pheochromocytoma in the population. All cases were histologically confirmed. The average annual incidence rate of pheochromocytoma was calculated. RESULTS: For the study period, 14 new cases (eight female and six male) of pheochromocytoma were diagnosed in the population of South Galicia. The average annual incidence rate in the population was 2.06 (range 0.0-3.93) per million. This incidence rate was significantly higher in the female population (2.26 vs. 1.84; P < 0.05). The mean age at diagnosis was 43 +/- 12 (range 21-65) years. Thirteen of the 14 cases were diagnosed in living patients (two discovered incidentally at operation) and one case was diagnosed at autopsy. One pheochromocytoma was located outside the adrenals. All but one tumour were benign. One patient had pheochromocytoma as part of the multiple endocrine neoplasia type IIa, and in four patients it was associated with neurofibromatosis (28.57%). Four of the 13 patients surgically treated had residual hypertension. CONCLUSIONS: The incidence of pheochromocytoma in our population is similar to that reported from other European countries. Routine screening for this disease is not recommended, but postoperative follow-up of the patients is needed. A wider study is necessary to confirm the high association with neurofibromatosis in our population.

Incidence of different forms of thyroid dysfunction and its degrees in an iodine sufficient area.

STUDY OBJECTIVE: The aim of the study was to determine the incidence of thyroid dysfunction in an iodine sufficient area (Vigo city, Galicia, North-West of Spain). DESIGN: Case-finding study during a 3-year (1990-1992) period. SUBJECTS: Subjects from a random sample of the population with abnormal results on FT4, sensitive-TSH or antithyroid autoantibodies. MEASUREMENTS: Thyroid size by ultrasound study. FT4 by RIA; TSA Ab by radio receptor assays; TSH, Tg Ab and TMS Ab by IRMA. MAJOR RESULTS: Overall incidence of thyroid dysfunction was 97.96 per 100,000 per year (CI 95% 78.86-117.06); female 162.45, male 17.44. Incidence rate of hyperthyroidism was 52.37 per 100,000 per year (CI 95% 38.41-66.36); 24.24 for Graves' disease, 11.63 for nodular hyperthyroidism, 13.57 for iatrogenic hyperthyroidism and 2.90 for others causes. Incidence rate of hypothyroidism was 45.58 per 100,000 per year (CI 95% 32.55-58.620 27.15 for hypothyroid autoimmune thyroiditis, 8.72 for postoperative hypothyroidism, 4.89 for miscellaneous hypothyroidism, 1.93 for amiodarone induced hypothyroidism and 2.90 for secondary hypothyroidism. CONCLUSIONS: This investigation provides extensive data on incidence of clinical and subclinical thyroid dysfunction and its different forms in an iodine sufficient area.

Increased incidence of thyrotoxicosis after iodine supplementation in an iodine sufficient area.

UNLABELLED: The aim of this study was to determine the incidence rate of thyrotoxicosis (TT) before and during dietary-iodine supplementation in an iodine-sufficient area. POPULATION: the study was carried out in Vigo, South Galicia (northwest of Spain), from January 1977 to December 1989. The mean population throughout the study period was 267,330 inhabitants (47% males and 53% females). From January 1985, a mandatory consumption of iodinized salt on the whole population started in Galicia. This region was considered as an iodine-deficient area but Vigo is an iodine-sufficient area. MEASUREMENTS: all newly diagnosed TT cases in Vigo city within the study period were included in this study. Diagnosis of TT was based on the clinical manifestations, an elevated level of T4 and suppressed TSH values. The difference between diffuse and nodular forms of goiter was assessed by scintigraphy. The average incidence rate (AIR) was determined in two periods, before (period A, 1977-1984) and during (period B, 1985-1989) iodine supplementation. RESULTS: the AIR throughout the whole study period was 4.89 new cases per 100,000 population, 95% confidence limits 4.16 to 5.63; AIR was 1.34 for males and 8.03 for females. AIR in period B was significantly higher with respect to period A, 7.68 and 3.10 per 100,000 respectively. The confidence interval for the difference was from -20.4 to 30.1, p < 0.05. The increase of the incidence of TT was comprised of both nodular and diffuse goiters. CONCLUSIONS: dietary iodinesupplementation in iodine-sufficient areas may induce an increase of the incidence of TT.(ABSTRACT TRUNCATED AT 250 WORDS)