Clinically applicable irreversible electroporation for eradication of micro-organisms.

Irreversible electroporation (IRE) damages cell membranes and is used in medicine for nonthermal ablation of malignant tumours. Our aim was to evaluate the antimicrobial effect of IRE. The pathogenic micro-organisms, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and Candida albicans were subjected to IRE. Survival was measured as a function of voltage and the number of pulses applied. Combined use of IRE and oxacillin for eradication of Staph. aureus was also tested. Log10 reduction in micro-organisms positively correlated with the number of applied pulses. The colony count of Strep. pyogenes and E. coli declined by 3·38 and 3·05 orders of magnitude, respectively, using an electric field of 2000 V and 100 pulses. Killing of Staph. aureus and P. aeruginosa was achieved with a double cycle of IRE (2000, 1500 V and repeated 1250 V respectively) of 50-100 IRE pulses. The addition of subclinical inhibitory concentrations of oxacillin to the Staph. aureus suspension prior to IRE led to total bacterial death, demonstrating synergism between oxacillin and IRE. Our results demonstrate that using IRE with clinically established parameters has a marked in vitro effect on pathogenic micro-organisms and highlights the potential of IRE as a treatment modality for deep-seated infections, particularly when combined with low doses of antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Irreversible electroporation (IRE) is utilized in interventional radiology to treat cancer patients. In this study we evaluated in vitro the antimicrobial effect of IRE. We demonstrated that using IRE with clinically established parameters has a marked effect on pathogenic micro-organisms and is synergistic to antimicrobials when both are combined. Our results point to the potential of IRE as a treatment modality for deep-seated infections.

Epidemiology of infective endocarditis in a tertiary-center in Jerusalem: a 3-year prospective survey.

BACKGROUND: Epidemiological features of infective endocarditis have changed during the last decades because of increases in the prevalence of health care exposure and of Staphylococcus aureus bloodstream infection. Consequently, the role of surgery is evolving. We aim to provide a contemporary profile of epidemiological, microbiological, and clinical features of infective endocarditis in a tertiary medical center, and identify predictors of mortality. METHODS: A prospective observational cohort study of consecutive adult patients with definite endocarditis according to the modified Duke criteria. Data were collected from January 1, 2009 through October 31, 2011 following a predefined case report form designed by the ICE-PCS. RESULTS: Among 70 endocarditis episodes, 25.7% involved prosthetic valves and 11.5% were device related. Forty-four percent of episodes were health-care associated. The predominant causative microorganism on native valve, prosthetic valve and device related endocarditis was Staphylococcus aureus (33.3%). Viridans group streptococci accounted for the majority of community-acquired endocarditis (36.1%). At least one complication occurred in 50% of the episodes. One third of the patients who had an indication for surgery were operated upon. Six month case fatality ratio was 40%. Sixty-five percent of patients with a contraindication to surgery died, compared with 9% and 28.5% who were treated surgically and medically, respectively. In multivariable analysis, age was a predictor of mortality. CONCLUSION: Compared with other series, we observed more health-care associated endocarditis, and a higher mortality. Nearly half of all deaths were in patients who had a contraindication to surgery. Careful evaluation of contraindications to surgery is warranted.

Probabilistic reasoning and clinical decision-making: do doctors overestimate diagnostic probabilities?

BACKGROUND: The "threshold approach" is based on a physician's assessment of the likelihood of a disease expressed as a probability. The use of Bayes' theorem to calculate disease probability in patients with and without a particular characteristic, may be hampered by the presence of subadditivity (i.e. the sum of probabilities concerning a single case scenario exceeding 100%). AIM: To assess the presence of subadditivity in physicians' estimations of probabilities and the degree of concordance among doctors in their probability assessments. DESIGN: Prospective questionnaire. METHODS: Residents and trained physicians in Family Medicine, Internal Medicine and Cardiology (n = 84) were asked to estimate the probability of each component of the differential diagnosis in a case scenario describing a patient with chest pain. RESULTS: Subadditivity was exhibited in 65% of the participants. The total sum of probabilities given by each participant ranged from 44% to 290% (mean 137%). There was wide variability in the assignment of probabilities for each diagnostic possibility (SD 16-21%). DISCUSSION: The finding of substantial subadditivity, coupled with the marked discordance in probability estimates, questions the applicability of the threshold approach. Physicians need guidance, explicit tools and formal training in probability estimation to optimize the use of this approach in clinical practice.

Breast cancer after breast augmentation with silicone implants.

BACKGROUND: Although epidemiological studies have failed to demonstrate an increased incidence of breast cancer in women who had undergone prior prosthetic augmentation mammoplasty (PAM), it has been reported that when breast cancer arises in this group it presents mostly in a palpable form and at a more advanced stage. This is thought to be secondary to suboptimal mammographic evaluation caused by the masking effect of the implant. This study was undertaken to determine, in our experience, whether breast cancer arising in women who had undergone PAM could be detected in a prepalpable form by mammography and whether it presented at a more advanced stage as compared with nonaugmented women with breast cancer. METHODS: The charts of 22 patients, treated by at least one of the authors, in whom 23 breast cancers developed after PAM (group A) were retrospectively reviewed. The comparison groups consisted of 611 nonaugmented patients who underwent 636 procedures for the treatment of primary breast cancer at our institution (group B) and the surveillance, epidemiology, and end results (SEER) data (group C). Parameters studied were mode of detection, tumor size, axillary lymph node involvement, and histopathology. RESULTS: No significant differences between the groups were found in mean tumor size (group A vs. group B), the incidence of preinvasive cancer (group A vs. group B) or axillary lymph node involvement (group A vs. group B and group A vs. group C). Breast-preserving surgery was performed significantly less in augmented patients (group A vs. group B). CONCLUSION: We conclude that prepalpable and preinvasive breast cancer can be detected in the PAM patient by mammography and that the stage of presentation in this group is not significantly different than in nonaugmented patients. Total mastectomy is preferred over breast-preserving procedures for the treatment of breast cancer in the PAM patient.

Breast-gut connection: origin of chenodeoxycholic acid in breast cyst fluid.

The notion that a breast-gut connection might modulate the microenvironment of breast tissue was supported by the finding that breast cyst fluid contains bile acids that are characteristically found in the intestines. To establish that the gut, rather than circulating steroid precursors, is the source of bile acids in breast cyst fluid, we gave two patients deuterium-labelled chenodeoxycholic acid (three 200 mg doses by mouth), starting 9 days before aspiration of breast cysts. The chenodeoxycholic acid concentration of seven samples of aspirated cyst fluid ranged from 42 to 94 mumol/L. The corresponding serum concentrations of chenodeoxycholic acid on the same day were 0.8 and 2.9 mumol/L, of which the labelled compound comprised 13.0% (0.38 mumol/L) and 28.2% (0.23 mumol/L). The deuterated chenodeoxycholic acid concentrations in cyst fluid were 0.79 and 1.26 mumol/L in two samples from patient 1 and 3.22 mumol/L in patient 2; these values are equivalent to 11-17% of the serum concentrations [corrected]. This study shows that intestinal bile acids rapidly gain access to cyst fluid. Further studies should investigate the mechanisms that govern the exchange processes and the maintenance of the high cyst fluid to plasma concentration gradients, and the biological half-lives of individual constituents.

Sensitivity of xenografts of human pancreatic adenocarcinoma in nude mice to heat and heat combined with chemotherapy.

The sensitivity of two human pancreatic adenocarcinomas (Capan-1 and Capan-2) to heat and heat combined with chemotherapy was studied using xenografts of the tumors in the foot of athymic nude mice. Heat was applied by immersion of the tumor in a water bath at 43.5 degrees for 1 hr. A single i.p. dose of mitomycin C, cisplatin, 5-fluorouracil, or 0.9% NaCl solution was given at 1 hr prior to treatment. Heat treatment alone significantly suppressed tumor growth (p less than 0.001), with 35% of the tumors showing complete regression. Combined treatment using heat plus chemotherapy yielded significantly greater suppression of tumor growth (p less than 0.05) with mitomycin for both tumors and with cisplatin or 5-fluorouracil for Capan-1. Combined treatment also gave higher rates of complete tumor regression: 55 and 64%, respectively, for Capan-1 and Capan-2 as compared with 18 and 47% for the respective tumors treated by heat alone. These observations suggest that human pancreatic carcinomas are sufficiently sensitive to heat combined with chemotherapeutic treatment to warrant a clinical trial of these modalities.