Biomedical subjects
Yaniv Almog
Publications and source records attributed to Yaniv Almog.
The effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases.
OBJECTIVE: Statins have pleiotropic effects that are independent of their lipid-lowering ability. We have previously shown that prior statin therapy is associated with a decreased risk of severe sepsis in patients admitted with acute bacterial infection. The aim of this study was to determine whether statin therapy is associated with a decreased risk of infection-related mortality. DESIGN: A prospective, observational, population-based study. SETTING: Tertiary university medical center. PATIENTS: Using a computerized database, 11,490 patients with atherosclerotic diseases were identified and followed for up to 3 yrs. Two groups of patients were compared: those receiving statins in the final month before follow-up termination and those who were not. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was infection-related mortality. Of the 11,362 patients included in the final analysis, 5,698 (50.1%) belonged to the statin group. Median follow-up was 19.8 months (interquartile range, 14.3-33.3). The risk of infection-related mortality was significantly lower in the statin compared with the no-statin group (0.9% vs. 4.1%), reflecting a relative risk of 0.22 (95% confidence interval, 0.17-0.28). Stepwise Cox proportional hazard survival analysis including a propensity score for receiving statins revealed that the protective effect of statins adjusted for all known potential confounders remained highly significant (hazard ratio, 0.37; 95% confidence interval, 0.27-0.52). CONCLUSIONS: Therapy with statins may be associated with a reduced risk of infection-related mortality. This protective effect is independent of all known comorbidities and dissipates when the medication is discontinued. If this finding is supported by prospective controlled trials, statins may play an important role in the primary prevention of infection-related mortality.
Amikacin dosing and monitoring in spinal cord injury patients: variation in clinical practice between spinal injury units and differences in experts' recommendations.
The objective of this article was to determine the current practice on amikacin dosing and monitoring in spinal cord injury patients from spinal cord physicians and experts. Physicians from spinal units and clinical pharmacologists were asked to provide protocol for dosing and monitoring of amikacin therapy in spinal cord injury patients. In a spinal unit in Poland, amikacin is administered usually 0.5 g twice daily. A once-daily regimen of amikacin is never used and amikacin concentrations are not determined. In Belgium, Southport (U.K.), Spain, and the VA McGuire Medical Center (Richmond, Virginia), amikacin is given once daily. Whereas peak and trough concentrations are determined in Belgium, only trough concentration is measured in Southport. In both these spinal units, modification of the dose is not routinely done with a nomogram. In Spain and the VA McGuire Medical Center, monitoring of serum amikacin concentration is not done unless a patient has renal impairment. In contrast, the dose/interval of amikacin is adjusted according to pharmacokinetic parameters at the Edward Hines VA Hospital (Hines, Illinois), where amikacin is administered q24h or q48h, depending on creatinine clearance. Spinal cord physicians from Denmark, Germany, and the Kessler Institute for Rehabilitation (West Orange, New Jersey) state that they do not use amikacin in spinal injury patients. An expert from Canada does not recommend determining serum concentrations of amikacin, but emphasizes the value of monitoring ototoxicity and nephrotoxicity. Experts from New Zealand recommend amikacin in conventional twice- or thrice-daily dosing because of the theoretical increased risk of neuromuscular blockade and apnea with larger daily doses in spinal cord injury patients. On the contrary, experts from Greece, Israel, and the U.S. recommend once-daily dosing and determining amikacin pharmacokinetic parameters for each patient. As there is considerable variation in clinical practice across spinal units and experts differ on ideal dosing and monitoring of amikacin therapy in spinal cord injury patients, there is an urgent need to develop best-practice guidelines.
Statins: panacea for sepsis?
Sepsis occurs when the immune system responds to a localised infection at a systemic level, thereby causing tissue damage and organ dysfunction. Statins have proven health benefits in many diseases involving vascular inflammation and injury. Recent animal data suggest that the administration of a statin before a sepsis-inducing insult reduces morbidity and improves survival. The immunomodulatory and anti-inflammatory effects of statins, collectively referred to as pleiotropic effects, lend biological plausibility to such findings. Limited human data hint at reduced mortality rates in bacteraemic patients, and a reduced risk of sepsis in patients with bacterial infections concurrently taking statins. These lines of evidence point to a potential new treatment and prevention modality for sepsis. The stage is set for randomised controlled clinical trials that will determine whether statins represent a safe and beneficial treatment in critically ill, septic patients and whether statins are effective at preventing sepsis in high-risk clinical settings.
Severe reversible myocardial depression in septic abortion.
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Do statins have a role in preventing or treating sepsis?
Statins have a variety of properties that are independent of their lipid lowering ability. These anti-inflammatory, antioxidant, immunomodulatory, and antiapoptotic features have been collectively referred to as pleiotropic effects. Severe sepsis is an intense infection-induced inflammatory syndrome that ultimately results in organ dysfunction. Because so many cascades are triggered during sepsis, merely blocking a single component may be insufficient to arrest the inflammatory process. A growing body of evidence suggests that statins may indeed have a protective effect against severe sepsis and reduce the rate of infection-related mortality. This novel primary prevention concept may have far-reaching implications for the future management of serious infections. Moreover, it was recently shown that statins potentially improve outcome after the onset of sepsis. The stage is now set for randomized clinical trials that will determine the precise role, if any, that statins may have in preventing and treating sepsis.
Plasma level of N terminal pro-brain natriuretic peptide as a prognostic marker in critically ill patients.
We studied whether N-terminal pro brain natriuretic peptide (NT-pro BNP) measured at intensive care unit admission is an independent predictor of mortality in critically ill patients. We conducted a prospective observational cohort study enrolling 78 patients with APACHE II scores more than 12. Serum NT-pro BNP and cardiac troponin T were measured at admission, and echocardiography was performed within 24 h. The primary end-point was 30-day mortality. The median NT-pro BNP levels of the 22 (28.2%) patients who died were significantly more frequent than that of those who survived (8328 versus 1016 pg/mL; P = 0.001). Patients with NT-pro BNP levels more than 1900 pg/mL had significantly more frequent mortality (47.2% versus 11.9%; P = 0.03). This group also had more frequent moderate to severe left ventricular dysfunction (30.6% versus 9.5%; P = 0.02) and abnormal cardiac troponin T levels (33.3% versus 14.3%; P = 0.05). Multivariate analyses adjusted for APACHE-II revealed that a NT-pro BNP level more than 1900 pg/mL is an independent predictor of mortality.
Myocardial infarction complicating critical illness.
Cardiac troponins are highly sensitive and specific indicators of myocardial injury. Although the mechanism of this injury is not entirely clear, it carries important prognostic information. Elevated serum levels of cardiac troponins have been described in a wide variety of conditions other than myocardial infarction (MI). The current study is an important first step in trying to determine the exact frequency of MI among critically ill patients with elevated troponin. At present, the rate of MI in these patients is unknown and its implications on outcome and management will have to await future prospective clinical trials.
Clinical characteristics and prognostic factors in patients with complicated acute coronary syndromes requiring prolonged mechanical ventilation.
Patients with acute coronary syndromes (ACSs) may develop serious multiorgan complications and require prolonged intensive care. Our aim was to characterize and identify factors that are associated with outcomes in these patients. We retrospectively identified 267 consecutive patients admitted to the coronary care unit for an ACS who required >3 days of mechanical ventilation. Multiple clinical and laboratory variables were correlated with mortality. Patients' ages were 68.3 +/- 10.9 years (mean +/- SD) and 165 (62%) were men. Seventy-six patients (29%) died within 30 days of admission, and the 1 year mortality was 46%. Moderate or severe left ventricular systolic dysfunction was found in 72% of the patients. Eighty-nine patients (33.3%) required vasopressors, of whom 64 (72%) did not survive 30 days. Among 127 patients who required antibiotics (48.3%), 30-day mortality was 53% compared with 4% among patients who did not require antibiotics (p <0.001). The 30-day mortality among patients who received both antibiotics and vasopressors was 64 of 87 patients (74%), and the 1-year mortality in this subgroup was 86.2%. Parameters found to be independent predictors of 30-day mortality were (in descending order): vasopressor requirement, use of antibiotics, peripheral vascular disease, ST-elevation myocardial infarction, renal failure, obesity and Killip class on admission. In conclusion, mortality among patients who require prolonged mechanical ventilation after an ACS is substantial. The main independent predictors of with mortality are the severity of heart failure and the presence of co-morbidities.
Catastrophic thromboses and severe thrombocytopenia during heparin therapy in a patient with anti-phospholipid syndrome.
Catastrophic anti-phospholipid syndrome (CAPS) is a medical emergency characterized by thromboses of multiple small vessels of internal organs and the brain. Herein we present a patient with primary anti-phospholipid syndrome who developed CAPS manifested by hepatic, renal and splenic artery thromboses, as well as cerebral venous thrombosis. The course was further complicated by severe thrombocytopenia and haemolytic anemia. Two episodes of catastrophic thrombosis developed within 24-36 h after the initiation of heparin therapy, suggesting a role of heparin in triggering thromboses. The patient had no anti-platelet-factor-4 antibodies in repeated measurements, making clinical diagnosis of heparin-induced thrombocytopenia unlikely. The possible role of heparin in induction of thromboses and its therapeutic implication are detailed.
The role of cardiac troponin I as a prognosticator in critically ill medical patients: a prospective observational cohort study.
INTRODUCTION: Myocardial injury is frequently unrecognized in intensive care unit (ICU) patients. Cardiac troponin I (cTnI), a surrogate of myocardial injury, has been shown to correlate with outcome in selected groups of patients. We wanted to determine if cTnI level measured upon admission is an independent predictor of mortality in a heterogeneous group of critically ill medical patients. METHODS: We conducted a prospective observational cohort study; 128 consecutive patients admitted to a medical ICU at a tertiary university hospital were enrolled. cTnI levels were measured within 6 h of admission and were considered positive (>0.7 ng/ml) or negative. A variety of clinical and laboratory variables were recorded. RESULTS: Both cTnI positive and negative groups were similar in terms of age, sex and pre-admission co-morbidity. In a univariate analysis, positive cTnI was associated with increased mortality (OR 7.0, 95% CI 2.44-20.5, p < 0.001), higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores and a higher rate of multi-organ failure and sepsis. This association between cTnI and mortality was more pronounced among elderly patients (>65 years of age). Multivariate analysis controlling for APACHE II score revealed that elevated cTnI levels are not independently associated with 28-day mortality. CONCLUSION: In critically ill medical patients, elevated cTnI level measured upon admission is associated with increased mortality rate. cTnI does not independently contribute to the prediction of 28-day mortality beyond that provided by APACHE II.
Prior statin therapy is associated with a decreased rate of severe sepsis.
BACKGROUND: Statins have anti-inflammatory properties that are independent of their lipid-lowering abilities. We hypothesized that statin therapy before the onset of an acute bacterial infection may have a protective effect against severe sepsis. The aim of this study was to determine whether patients treated with statins develop severe sepsis less frequently. METHODS AND RESULTS: In this prospective observational cohort study, consecutive patients admitted with presumed or documented acute bacterial infection were enrolled. The primary outcomes were the rate of severe sepsis and intensive care unit (ICU) admission. Of the 361 patients enrolled, 82 (22.7%) were treated with statins before their admission. Both groups had a similar severity of illness on admission. Severe sepsis developed in 19% of patients in the no-statin group and in only 2.4% of the statin group (P<0.001). Statin treatment was associated with a relative risk of developing severe sepsis of 0.13 (95% CI, 0.03 to 0.52) and an absolute risk reduction of 16.6%. The overall ICU admission rate was 10.2% (37/361): 12.2% of the no-statin group required ICU admission, whereas in the statin group only 3.7% were admitted to the ICU (P=0.025), reflecting a relative risk of ICU admission of 0.30 (95% CI, 0.1 to 0.95). CONCLUSIONS: Prior therapy with statins may be associated with a reduced rate of severe sepsis and ICU admission. If supported by prospective controlled trials, statins may have a role in the primary prevention of sepsis.
Malignant ascites presenting as abdominal compartment syndrome.
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Sub-arachnoid hemorrhage following cardiopulmonary resuscitation.
We report the case of a 20-year-old male who developed unexplained sub-arachnoid haemorrhage following cardiopulmonary resuscitation. Computed tomography and lumbar puncture performed within 24 h were normal. A CT performed on day 5 revealed massive sub-arachnoid hemorrhage. The patient expired due to brain herniation. We conclude that sub-arachnoid hemorrhage (SAH) may be a late complication of aborted sudden death. We suggest ischaemia-reperfusion injury as a possible mechanism.
Carcinoma of the colon presenting as Streptococcus salivarius sepsis.
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A man with interstitial pneumonia and pancytopenia during radiotherapy.
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Gram-negative cellulitis complicating cirrhosis.
Gram-negative infections are common in patients with cirrhosis, but skin infections are usually caused by gram-positive cocci. Gram-negative bacteria should be considered as a potential etiologic agent in patients with cirrhosis and severe bullous cellulitis. Culture of the bullous fluid may facilitate diagnosis and management. Early recognition is important because the course of the disease is usually rapid and fatal. We report 4 cases of fulminant gram-negative bullous cellulitis and septic shock in patients with cirrhosis.
Pharmacokinetic dosing of aminoglycosides: a controlled trial.
PURPOSE: To evaluate whether individualized pharmacokinetic dosing of aminoglycosides can reduce nephrotoxicity and improve the outcome of patients with gram-negative sepsis. METHODS: We conducted a prospective controlled trial at a tertiary care university hospital. Eighty-one patients with suspected or documented gram-negative infections were enrolled. All were treated with either gentamicin or amikacin, according to clinical judgement. Patients were allocated to one of two groups based on the last digit (odd/even) of their identification number. In the study group (pharmacokinetic dosing) of 43 patients, plasma aminoglycoside levels were determined 1 hour after initiation of drug infusion and 8 to 16 hours later to estimate the elimination half-life and volume of distribution, from which the subsequent dosage schedule was calculated. Target peak plasma levels were 20 microg/mL for gentamicin and 60 microg/mL for amikacin. Target trough levels were <1 microg/mL for both drugs. The control group (fixed once-daily dosing) consisted of 38 patients who were prescribed single daily doses of gentamicin or amikacin. The primary endpoints were renal toxicity (> or = 25% increase in serum creatinine level or a serum creatinine level > or = 1.4 mg/dL) and 28-day mortality. RESULTS: The two study groups were similar in age, sex, indications for therapy, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and clinical assessment at baseline. Although the pharmacokinetic group received significantly greater doses of aminoglycosides than did the once-daily group, the incidence of nephrotoxicity was significantly lower in the pharmacokinetic group (5% [2/43] vs. 21% [8/38], P = 0.03). There was no statistically significant difference in 28-day mortality (27% [12/43] vs. 22% [8/38], P = 0.3). CONCLUSION: These results suggest that individualized pharmacokinetic dosing of aminoglycosides reduces the incidence of nephrotoxicity and allows the use of greater doses of aminoglycosides.