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Jonathan Cohen

Publications and source records attributed to Jonathan Cohen.

At least 73 records · Page 4Linked to original sources
PubMed2004

Family history is a major determinant of subclinical peripheral arterial disease in young adults.

BACKGROUND: Cardiovascular disease is prevalent in first-degree relatives of young adults with premature-onset peripheral arterial occlusive disease (premature PAD), but it is not known whether the genetic influence is independent of other risk factors, the most prevalent of which is smoking. This study was performed to determine the relative contributions of family history and smoking to the development of occult PAD in siblings of patients with premature PAD. METHODS: The prevalence of occult PAD was determined with carotid, abdominal, and lower extremity duplex ultrasound scanning in 50 asymptomatic siblings (25 men, 25 women) of patients with premature PAD (onset 20 cigarettes/day) and 50 nonsmokers. RESULTS: Duplex ultrasound scans demonstrated raised arterial lesions in 20 asymptomatic siblings (40%), 20 heavy smokers (40%), and 2 nonsmoking control subjects (4%), resulting in 42 affected and 108 unaffected subjects. As expected, smokers were far more likely to have arterial lesions than were nonsmokers (odds ratio [OR], 11.19; 95% confidence interval [CI], 4.1-30.7; P <.0001). Individuals with a family history of premature PAD were almost three times more likely to have arterial lesions than those with no family history of cardiovascular disease (OR, 2.76; 95% CI, 1.3-5.8; P =.006). Stratified and multivariable logistic regression indicated no interaction between smoking and family history, indicating simple additive effects on PAD. CONCLUSIONS: Family history is a major determinant of occult PAD in young adults, and is at least as important as standard atherosclerotic risk factors. A high proportion of heavy smokers have clearly detectable lesions even though asymptomatic. Smoking and family history act additively to increase the risk for premature PAD.

Arteriosclerosis↗
PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: We used a modified Delphi methodology for grading recommendations, built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. RESULTS: Key recommendations, listed by category and not by hierarchy, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; early administration of broad-spectrum antibiotic therapy; reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; a usual 7-10 days of antibiotic therapy guided by clinical response; source control with attention to the method that balances risks and benefits; equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; vasopressor preference for norepinephrine and dopamine; cautious use of vasopressin pending further studies; avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; avoidance of supranormal oxygen delivery as a goal of therapy; stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7-9 g/dL; appropriate use of fresh frozen plasma and platelets; a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; a semirecumbent bed position unless contraindicated; protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; avoidance of neuromuscular blockers, if at all possible; maintenance of blood glucose <150 mg/dL after initial stabilization; equivalence of continuous veno-veno hemofiltration and intermittent hemodialysis; lack of utility of bicarbonate use for pH > or =7.15; use of deep vein thrombosis/stress ulcer prophylaxis; and consideration of limitation of support where appropriate. Pediatric considerations included a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic end points; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control. CONCLUSION: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that are hoped to translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually and even more rapidly as some important new knowledge becomes as available.

Adult↗
PubMed2004

New method of classifying infections in critically ill patients.

OBJECTIVE: To develop a systematic classification describing the contribution made by infection to the outcome from sepsis. CONTEXT: The emergence of effective therapies for sepsis means that accurate methods of risk assessment are of increasing importance. Although there are well-validated instruments for describing risk factors in the host, the contribution made by the infection is less well served. DESIGN AND METHODS: A systematic literature review of the English language literature published during the last 30 yrs of studies describing the outcome of infections, categorized by micro-organism and site of infection. RESULTS: We surveyed 510 published articles including 55,854 clinical infections, and we generated specific risk codes for bacteremia, meningitis, pneumonia, skin and soft tissue infections, peritonitis, and urinary tract infections. Both the nature of the organisms and the site of infection have a significant impact on survival from sepsis, and there is a significant interaction between them. CONCLUSION: We have described a novel approach to permit a better assessment of the contribution made by the infection to mortality in patients with sepsis or septic shock.

Communicable Diseases↗
PubMed2004

Diagnosis of infection in sepsis: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for the diagnosis of infection in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSIONS: Obtaining a precise bacteriological diagnosis before starting antibiotic therapy is, when possible, of paramount importance for the success of therapeutic strategy during sepsis. Two to three blood cultures should be performed, preferably from a peripheral vein, without interval between samples to avoid delaying therapy. A quantitative approach is preferred in most cases when possible, in particular for catheter-related infections and ventilator-associated pneumonia. Diagnosing community-acquired pneumonia is complex, and a diagnostic algorithm is proposed. Appropriate samples are indicated during soft tissue and intraabdominal infections, but cultures obtained through the drains are discouraged.

Abdomen↗
PubMed2003

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.

OBJECTIVE: In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were to "provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well. The general definitions introduced as a result of that conference have been widely used in practice, and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. DESIGN: Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the Society of Critical Care Medicine (SCCM), The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). METHODS: 29 participants attended the conference from Europe and North America. In advance of the conference, subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters. The present manuscript serves as the final report of the 2001 International Sepsis Definitions Conference. CONCLUSION: 1. Current concepts of sepsis, severe sepsis and septic shock remain useful to clinicians and researchers. 2. These definitions do not allow precise staging or prognostication of the host response to infection. 3. While SIRS remains a useful concept, the diagnostic criteria for SIRS published in 1992 are overly sensitive and non-specific. 4. An expanded list of signs and symptoms of sepsis may better reflect the clinical response to infection. 6. PIRO, a hypothetical model for staging sepsis is presented, which, in the future, may better characterize the syndrome on the basis of predisposing factors and premorbid conditions, the nature of the underlying infection, the characteristics of the host response, and the extent of the resultant organ dysfunction.

Humans↗
PubMed2003

Expression of lymphotoxin-beta (LT-beta) in chronic inflammatory conditions.

Functional studies in gene-knockout and transgenic mice systems have shown that lymphotoxin-alpha and lymphotoxin-beta (LT-alpha and LT-beta) are of fundamental importance in peripheral lymphoid organ development, but it remains unclear what role these cytokines have to play in the adult immune response and in the pathogenesis of disease. In this study, a polyclonal anti-serum to human LT-beta was used to investigate the distribution of LT-beta by immunohistochemistry in normal and diseased tissues. In the gut, lymph nodes, spleen, and tonsil, there was some LT-beta present on a variety of lymphoid cell types. In contrast, strong staining for LT-beta was observed on plasma cells and a subpopulation of CD4+ T cells in tissues affected by chronic inflammatory disease or infection, for example in inflammatory bowel disease, and in lymph nodes obtained from patients with sarcoidosis and tuberculosis. In tuberculous and sarcoid lymph nodes, LT-beta expression also occurred on some but not all epithelioid histiocytes within granulomas and on multi-nucleated giant cells. These findings support a role for LT-beta in human disease and suggest that it might represent a therapeutic target in a variety of common infective or inflammatory disorders.

Adult↗
PubMed2003

Readmission to the intensive care unit after "fast-track" cardiac surgery: risk factors and outcomes.

BACKGROUND: The introduction of "fast-track" management into cardiac surgery has significantly shortened the intensive care unit (ICU) length of stay. Readmission to the ICU, traditionally used as a quality index, has not been investigated in these patients. The aim of this study was to assess the causes, risk factors, and outcomes associated with readmission to the ICU. METHODS: All patients undergoing open-heart surgery in a tertiary care, university-affiliated center were included in this prospective observational study. Preoperative and intraoperative data as well as ICU outcome were noted in all patients. RESULTS: Over the 27-month study period,1,613 patients were targeted for fast track management (discharge from ICU on the first postoperative day). The readmission rate was 3.29% (53 patients). Forty-three percent of readmissions occurred within 24 hours of discharge usually because of pulmonary problems (43%) or arrhythmias (13%). Readmission was associated with a prolonged ICU stay (105 +/- 180.0 versus 19.2 +/- 2.4 hours of initial ICU stay) and worse outcome: the only patients who died (6 of 53, 11.3%) were in this group. On multivariate analysis, a Bernstein-Parsonnet risk estimate more than 20 strongly predicted readmission (odds ratio, 3.08; 95% confidence interval, 1.43 to 6.69). CONCLUSIONS: Among a homogeneous group of patients targeted for fast-track management after cardiac surgery, readmission although uncommon is associated with a longer second ICU stay and significant mortality. The recognition of specific risk factors may allow for appropriate modification of the postoperative course.

Adult↗
PubMed2003

Endoscopic treatment compared with medical therapy for the prevention of recurrent ulcer hemorrhage in patients with adherent clots.

BACKGROUND: Two recent randomized, controlled trials have demonstrated efficacy for combination endoscopic therapy in the management of bleeding peptic ulcer with adherent clot. The aim of this study was to determine the effectiveness of this technique in a clinical practice setting. METHODS: Medical records of consecutive patients, seen from January 1992 through December 1999, with severe ulcer hemorrhage and non-bleeding adherent clots resistant to target irrigation were reviewed. The decision for combination endoscopic therapy (epinephrine injection, removal of adherent clot, treatment of underlying stigmata) or medical therapy was left to the discretion of the endoscopist. RESULTS: Of 244 patients with adherent clots, 138 (56.6%) had endoscopic therapy and 106 (43.4%) were managed with medical therapy alone. The baseline characteristics of the two groups were similar, except for older age in the endoscopic therapy group. Recurrence of bleeding within 7 days of endoscopy was significantly less frequent in the endoscopic therapy group than the medical therapy group (respectively, 8.7% vs. 27.4%; adjusted odds ratio 0.07 95% CI [0.02, 0.22], p<0.001). Median hospital stay (6.0 vs. 8.0 days; p<0.001), median number of red blood cell transfusions after endoscopy (2.0 vs. 3.0 units; p=0.01), the need for repeat endoscopy (9.4% vs. 26.4%; p<0.001), and recurrent bleeding within 30 days (10.1% vs. 28.3%; p<0.001) were significantly lower in the endoscopic therapy group. In addition, the need for ulcer surgery (5.8% vs. 9.4%; p=0.28) and 30-day mortality (3.6% vs. 7.5%; p=0.18) were lower in the endoscopic therapy group, although these differences were not statistically significant. Endoscopic complications were uncommon (1.4% vs. 0.9%; p=1.00). CONCLUSIONS: Combination endoscopic treatment of ulcers with an adherent clot was associated with a significant reduction in recurrent ulcer hemorrhage compared with medical therapy alone. These findings confirm that the efficacy of combination endoscopic therapy demonstrated in carefully designed, randomized, controlled clinical trials can be reproduced when this technique is applied in a clinical practice setting. However, combination therapy did not significantly reduce the need for ulcer surgery or 30-day mortality.

Age Factors↗
PubMed2003

Hypocomplementemic urticarial vasculitis with angioedema, a rare presentation of systemic lupus erythematosus: rapid response to rituximab.

We report a case of hypocomplementemic urticarial vasculitis and recurrent angioedema in a patient with systemic lupus erythematosus unresponsive to mycophenolate mofetil, high-dose methylprednisolone, and intravenous immunoglobulin that responded rapidly to rituximab. Rituximab is a monoclonal antibody against CD20 transmembrane protein on the surface of mature and malignant B cells. No adverse effects occurred during or after therapy, and the patient was discharged from the hospital for outpatient rituximab infusion and follow-up care.

Adult↗
PubMed2003

Recent developments in the identification of novel therapeutic targets for the treatment of patients with sepsis and septic shock.

The overall mortality in patients with sepsis is approximately 30%; this figure increases to 50% or higher in patients with septic shock, and sepsis continues to be seen as a major clinical challenge. The recent success of several important trials has fuelled interest in further therapeutic developments. Here, I review the many different strategies that are being investigated, focusing in particular on those that are in late pre-clinical or early clinical development. These can be broadly divided into three groups: strategies aimed at bacterial targets, strategies aimed at disorders of immune regulation in the host, and finally, other novel strategies based on modifying host response; which, if any, of these will prove successful in large clinical trials is unknown. Nevertheless, the fact that sepsis has finally proved tractable as a target for new drug development lends support to those who believe that at least some of the compounds identified in this paper will prove to have clinical benefit.

Chemistry, Pharmaceutical↗
PubMed2003

Application of a rat model of streptococcal shock to evaluate on-line hemoperfusion and removal of circulating superantigens.

OBJECTIVE: To evaluate the efficacy of on-line hemoperfusion for the removal of circulating superantigens in a rat model of streptococcal shock. DESIGN: In vitro and experimental animal studies. SETTING: University research laboratories. INTERVENTIONS: Chemically modified polystyrene-based composite fiber reinforced with polypropylene was formulated in discs and used to evaluate the removal of superantigenic toxins from culture supernatants in vitro, and from blood in vivo. MEASUREMENTS AND MAIN RESULTS: Incubation of streptococcal supernatant with a single disc reduced the concentration of the superantigen streptococcal pyrogenic exotoxin A from 90.9 +/- 12.7 ng/mL with the control fiber to 32.5 +/- 3.6 ng/mL with active fiber (p <.001). The active discs also brought about a dose-dependent reduction in mitogenic activity that was highly significant (counts reduced from 82,133 +/- 2747 using three control discs to 26,307 +/- 3547 with three active discs [p <.001]). Beginning 6 hrs after infection, animals were hemoperfused for 3 hrs over columns containing control or active fiber. At the end of the treatment period, there was a significant decrease in the number of circulating bacteria in the active group (3.5 x 10(4) vs. 3.1 x 10(3) colony-forming units/mL, p<.05). However, bacterial counts subsequently increased and by 15 hrs and at all subsequent time points, the number of circulating bacteria was no different between the two groups. There was a highly significant and sustained difference in circulating streptococcal pyrogenic exotoxin A levels between the groups. Streptococcal pyrogenic exotoxin A levels at 9 hrs were 19.9 ng/mL in the controls vs. 2.1 ng/mL in the active group (p =.05). Animals perfused over active fibers had a highly significant survival advantage compared with control or nonperfused groups (p <.01). CONCLUSIONS: Hemoperfusion and on-line removal of superantigens merits further study as a possible treatment strategy for streptococcal shock syndromes. The mechanism by which the fibers are operating requires further investigation.

Animals↗
PubMed2003

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.

OBJECTIVE: In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well." The general definitions introduced as a result of that conference have been widely used in practice and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. DESIGN: Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the SCCM, The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). METHODS: The conference was attended by 29 participants from Europe and North America. In advance of the conference, five subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters. The subgroups corresponded electronically before the conference and met in person during the conference. A spokesperson for each group presented the deliberation of each group to all conference participants during a plenary session. A writing committee was formed at the conference and developed the current article based on executive summary documents generated by each group and the plenary group presentations. The present article serves as the final report of the 2001 International Sepsis Definitions Conference. CONCLUSION: This document reflects a process whereby a group of experts and opinion leaders revisited the 1992 sepsis guidelines and found that apart from expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience, no evidence exists to support a change to the definitions. This lack of evidence serves to underscore the challenge still present in diagnosing sepsis in 2003 for clinicians and researchers and also provides the basis for introducing PIRO as a hypothesis-generating model for future research.

Humans↗