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Biomedical subjects

Jonathan Cohen

Publications and source records attributed to Jonathan Cohen.

At least 19 recordsLinked to original sources

Comparison of metabolic monitors in critically ill, ventilated patients.

OBJECTIVE: We compared the Deltatrac II, the M-COVX, and the Evita 4 metabolic monitoring devices under clinical conditions. METHODS: A prospective simultaneous clinical comparison was performed in a general intensive care department of a tertiary university hospital in 43 ventilated, critically ill patients. The monitors were compared simultaneously. After 30 min of steady state, oxygen consumption per unit time, carbon dioxide consumption per unit time, resting energy expenditure, and respiratory quotient were recorded for the Deltatrac II; the same parameters in addition to end-tidal carbon dioxide and fraction of inspired oxygen were recorded for the M-COVX; and carbon dioxide consumption per unit time, end-tidal carbon dioxide, and fraction of inspired oxygen were recorded for the Evita 4. Pulmonary gas-exchange measurements from the Deltatrac II and resting energy expenditure and respiratory quotient from the M-COVX were obtained after 30 min. The other parameters were calculated from the last five measurements obtained at the end of the study period. RESULTS: A good correlation was found between oxygen consumption per unit time and resting energy expenditure as obtained from the Deltatrac II and the M-COVX (r = 0.76 and 0.75, respectively; P < 0.001), but the correlation was lower between carbon dioxide consumption per unit time as obtained from the Deltatrac II and the M-COVX or Evita 4 (r = 0.67 and 0.48, respectively). Agreement between the different methods did not reach clinical acceptability, exceeding a 20% difference using the Bland-Altman statistical methods. CONCLUSION: Poor agreement was found between the Deltatrac II and M-COVX or Evita 4 metabolic monitors, despite a good correlation between measurements, leading to the conclusion that the M-COVX and Evita 4 provide less accurate measurements of metabolic gas exchange in stable ventilated patients. These devices can be used for daily nutritional assessment and continuous monitoring, but the Deltatrac II remains the method of choice for metabolic measurement.

Adult↗

The TCR Vbeta signature of bacterial superantigens spreads with stimulus strength.

Superantigens (Sags) induce large-scale stimulation of T lymphocytes by a mechanism distinct from conventional antigen presentation, involving direct MHC binding and stimulation of TCR families based on Vbeta gene usage. The specific Vbeta targets of a given Sag have, since the earliest studies in murine models, been considered a hallmark of that toxin. Bacterial Sags are implicated in the aetiology of a wide range of human diseases, although their role has been most clearly defined in toxic shock syndrome. While Sags have been defined by the Vbeta-specific changes in T cell repertoire they induce, human studies of in vitro stimulation or analysis of cells from infected patients have produced inconsistent findings. Here we have evaluated the contribution of HLA allelic polymorphisms and strength of stimulus to this response. We show that there are differences in binding and presentation of the staphylococcal Sag, staphylococcal enterotoxin A (SEA), by different HLA-DR alleles. We also show that the TCR Vbeta response, previously thought to be a fixed property defining a given Sag, varies with stimulus strength such that a broader repertoire of response is seen at higher concentrations or following presentation by high-binding class II types. Responses of human Vbeta8 and Vbeta1 to SEA, Vbeta5 to SEB and of Vbeta12 and Vbeta13 to streptococcal pyrogenic exotoxin A are absolutely dependent on stimulus strength. These findings have important implications for heterogeneity in the response to Sags and the consequent differences in susceptibility to severe toxic shock.

Antigen Presentation↗

The Neo-Papilla: a new modification of porcine ex vivo simulators for ERCP training (with videos).

BACKGROUND: Computer simulators, live pigs, and ex vivo porcine simulators are used for training in ERCP. The location of the porcine biliary orifice in the proximal duodenum is dissimilar to human anatomy, making the endoscopy experience less realistic. In addition, in native porcine anatomy, the pancreatic duct enters the duodenum distal to the biliary orifice, limiting the teaching of pancreatic techniques and selective duct cannulation. OBJECTIVE: To overcome these limitations, we aimed to construct a Neo-Papilla that could be incorporated into an ex vivo model. DESIGN: We attached chicken heart tissue to the porcine duodenum, with integrated porcine arteries that resembled an artificial common bile duct and a pancreatic duct. SETTING: The simulator was presented and evaluated at 2 major GI endoscopy conferences. MAIN OUTCOME MEASUREMENTS: The feasibility and the realism of this prototype was tested by 9 recognized ERCP experts who rated this model in comparison to other teaching models for ERCP by recollection of prior experience. RESULTS: The Neo-Papilla was more prominent and more distally located than the native porcine papilla. The experts rated this modification superior to existing models in its usefulness as an educational tool. LIMITATIONS: Pilot study. CONCLUSIONS: We demonstrated the technical feasibility of a real-tissue Neo-Papilla modification of porcine ex vivo simulators, more closely approximating the natural anatomy. This new model should facilitate ERCP training. Formal validation studies are warranted.

Ampulla of Vater↗

Human intravenous immunoglobulin for experimental streptococcal toxic shock: bacterial clearance and modulation of inflammation.

OBJECTIVES: Polyclonal human intravenous immunoglobulin (IVIG) has been advocated as an adjunct to therapy in severe invasive streptococcal toxic shock because of its ability to neutralize superantigen toxins. The aim of this study was to assess IVIG therapeutic efficacy in an experimental model of streptococcal toxic shock. METHODS: To confirm the in vitro activity of IVIG against the Streptococcus pyogenes strain used in the study, IVIG was tested for superantigen neutralizing and bacterial opsonizing activity prior to in vivo studies. To evaluate the in vivo effects of IVIG in terms of microbiological outcome and disease severity in a superantigen-sensitive transgenic model of streptococcal shock, HLA-DQ transgenic mice were treated with IVIG either at the time of infection or after infection with S. pyogenes. Antibiotics were included in some studies. RESULTS: The IVIG preparation neutralized superantigenicity of S. pyogenes in vitro and enhanced bacterial killing in a whole blood assay. When given to mice at the time of S. pyogenes infection, IVIG neutralized circulating superantigens and reduced systemic inflammatory response. Remarkably, IVIG-enhanced systemic clearance of bacteria and enhanced neutrophil infiltrate into the infected tissues. However, when used in combination with penicillin and clindamycin in a delayed treatment setting, IVIG did not confer additional therapeutic benefit, in terms of inflammatory response, bacterial clearance or survival. CONCLUSIONS: IVIG monotherapy can confer benefit in experimental streptococcal shock, but extension of these findings to the clinical situation will require further evaluation.

Animals↗

Successful organ transplantation from donors with Acinetobacter baumannii septic shock.

Donor bacteremia with severe sepsis, especially due to gram-negative organisms, has been considered a contraindication to transplantation. Over a 6-month period we prospectively collected standardized data on all brain-dead, heart-beating organ donors with gram negative bacteremia and septic shock and the recipients of their organs in hospitals throughout Israel. Donors were treated with appropriate antibiotics for at least 48 hr prior to organ retrieval while recipients received 7 days of culture-specific antibiotics following transplantation. In total, 12 organs were transplanted (5 kidneys, 2 livers, 3 lungs and 2 hearts) from 3 donors with Acinetobacter baumannii bacteremia and septic shock. All patients were alive with good graft function 60 days following transplantation, apart from one of the heart recipients who died of primary nonfunction on the second postoperative day. Two recipients developed postoperative infections, none with Acinetobacter sp. (one Pseudomonas sp. urinary tract infection, one Klebsiella sp. central venous catheter sepsis).

Acinetobacter Infections↗

Computerized energy balance and complications in critically ill patients: an observational study.

BACKGROUND AND AIMS: An accurate energy balance is difficult to achieve in hospitalized patients. The aim of the study was to measure the daily cumulative energy balance in critically ill patients receiving mechanical ventilation using a bedside computerized information system (CIS), and to assess its impact on outcome. METHODS: Fifty intensive care unit (ICU) patients (33 male, 17 female, mean age 59 +/- 18 years) were prospectively followed. Mean body mass index was 26.85 +/- 5.23 kg/m2 and mean APACHE II score, 23.1 +/- 7.7. Resting energy expenditure was measured daily with indirect calorimetry (Deltatrac II, Datex-Ohmeda, Finland), and daily macronutrient intake was measured with a bedside CIS (iMDsoft, Israel) connected to all caloric sources. End-point measures were morbidity (acquired organ dysfunction, pressure sores, need for surgery) and mortality. One- and two-way analysis of variance and stepwise logistic regression for predicted probability were used for statistical analysis. RESULTS: Mean energy intake was 1512 kcal/day and mean cumulative energy balance for an overall ICU stay of 566 days was -4767 kcal (range +4747 to -17,274). A strong association of maximum negative energy balance with adult respiratory distress syndrome (P = 0.0003), sepsis (P = 0.0035), renal failure (P = 0.0001), pressure sores (P = 0.013), need for surgery (P = 0.023), and total complication rate (P = 0.0001), but not with length of ventilation, ICU stay, or hospitalization, or mortality. CONCLUSIONS: Negative energy balance may be correlated with the occurrence of complications in the ICU. The bedside CIS provides accurate information on energy balance in critically ill patients and may allow for early detection and prevention of severe negative energy balance and complications.

APACHE↗

Multicenter, randomized, controlled trial of virtual-reality simulator training in acquisition of competency in colonoscopy.

BACKGROUND: The GI Mentor is a virtual reality simulator that uses force feedback technology to create a realistic training experience. OBJECTIVE: To define the benefit of training on the GI Mentor on competency acquisition in colonoscopy. DESIGN: Randomized, controlled, blinded, multicenter trial. SETTING: Academic medical centers with accredited gastroenterology training programs. PATIENTS: First-year GI fellows. INTERVENTIONS: Subjects were randomized to receive 10 hours of unsupervised training on the GI Mentor or no simulator experience during the first 8 weeks of fellowship. After this period, both groups began performing real colonoscopies. The first 200 colonoscopies performed by each fellow were graded by proctors to measure technical and cognitive success, and patient comfort level during the procedure. MAIN OUTCOME MEASUREMENTS: A mixed-effects model comparison between the 2 groups of objective and subjective competency scores and patient discomfort in the performance of real colonoscopies over time. RESULTS: Forty-five fellows were randomized from 16 hospitals over 2 years. Fellows in the simulator group had significantly higher objective competency rates during the first 100 cases. A mixed-effects model demonstrated a higher objective competence overall in the simulator group (P < .0001), with the difference between groups being significantly greater during the first 80 cases performed. The median number of cases needed to reach 90% competency was 160 in both groups. The patient comfort level was similar. CONCLUSIONS: Fellows who underwent GI Mentor training performed significantly better during the early phase of real colonoscopy training.

Clinical Competence↗

Evolution of endoscopy simulators and their application.

Significant advances already have been made in the use of simulators for teaching and training in GI endoscopy. Indeed, during the past decade the evolution and improvement of these devices is readily apparent with each passing year. Doubtless, these advances have led to the increased availability and popularity of simulator-based hands-on workshops. Simulator-based skills assessment remains a relatively undeveloped field, awaiting increased realism and the development and validation of proper tests. Still, static models, ex vivo artificial models, ex vivo animal models, and computer simulators collectively represent a substantial and powerful tool for education and training in GI endoscopy. It is easy to foresee a day when hands-on training using simulators will be readily available outside the gastroenterology fellowship setting. With the progression of technology and the continuous introduction of new devices and procedures will come a parallel, compelling need for hands-on, simulator-based experience with all such new tools and techniques.

Animals↗

Endoscopy simulators: lessons from the aviation and automobile industries.

Individuals who are interested in using technology to promote education and quality assurance in endoscopy may turn to aviation and driver's test simulation for guidance. Of course the forces driving the innovation and the regulation governing these fields are entirely different from the ones faced in endoscopy. However, some of the general principles of how simulators can enhance training and how their strengths can be put to optimal use are quite pertinent to those individuals interested in the ongoing evolution of endoscopy simulation.

Automobile Driver Examination↗