Presence Of Sepsis Research Articles

Low insulin-like growth factor-1 and hypocholesterolemia as mortality predictors in acute kidney injury in the intensive care unit*

To assess the role of insulin-like growth factor-1 and cholesterol as predictors of acute kidney injury mortality in intensive care unit patients. Prospective cohort study. Multidisciplinary adult intensive care unit (24 beds). Adult patients with acute kidney injury at intensive care unit admission for an 11-month period were considered and a total of 56 patients were admitted in the study. None. At intensive care unit admission serum insulin-like growth factor-1 (ng/mL), total cholesterol (mg/dL), albumin (g/dL), transferrin (mg/dL), total lymphocyte count, triceps skinfold thickness, arm muscle area, and Subjective Global Nutritional Assessment were evaluated. Insulin-like growth factor-1 was significantly lower in nonsurviving as compared with surviving patients (48.5 +/- 24.4 vs. 70.8 +/- 39.9; p = 0.044), as well as cholesterol (80.3 +/- 35.7 vs. 147.4 +/- 53.1; p < 0.001) and albumin (1.9 +/- 0.4 vs. 2.4 +/- 0.7; p = 0.018). Groups were similar regarding transferrin, lymphocyte, triceps skinfold thickness, arm muscle area, and subjective global nutritional assessment. A binary logistic regression model based on insulin-like growth factor-1 < or = median (50.6 ng/mL), presence of sepsis, oliguria, and cholesterol < or = median (96 mg/dL) identified insulin-like growth factor-1 (odds ratio = 7.73; 95% confidence interval 1.19-49.87; p = 0.032), sepsis (odds ratio = 7.28; 95% confidence interval 1.29-40.89; p = 0.024), oliguria (odds ratio = 8.7; 95% confidence interval 1.10-68.77; p = 0.040) and cholesterol (odds ratio = 10.94; 95% confidence interval 1.89-63.29; p = 0.008) as independent covariate for death. Decreased levels of insulin-like growth factor-1 and cholesterol were clearly related to higher mortality. The close correlation of insulin-like growth factor-1 with nutritional status, its serum stability, and short-half life makes it a suitable candidate for an early and sensitive marker for intensive care unit acute kidney injury mortality.

Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury

Objectives:To determine whether baseline plasma levels of the receptor for advanced glycation end products (RAGE), a novel marker of alveolar type I cell injury, are associated with the severity and...

Characteristics and outcomes of patients receiving a medical emergency team review for respiratory distress or hypotension

Purpose To describe the characteristics and outcomes of patients receiving a medical emergency team (MET) review for the MET syndromes of respiratory distress or hypotension and to assess the effect of delayed MET activation on their outcomes. Materials and Methods We retrospectively analyzed the medical records of 2 cohorts of 100 patients for each of the MET syndromes of respiratory distress and hypotension. We collected information on patient demographics, comorbidities, presence of sepsis, and patient outcome. We documented the presence and duration of delayed MET activation. Results Patients with respiratory distress were more likely to be postoperative (40% vs 28%, P = .07), but less likely to have a history of congestive cardiac failure (12% vs 22%, P = .06). Sepsis was present in 58% of cases. The hospital mortality for MET calls due to respiratory distress and hypotension was 38% and 35%, respectively ( P = .77). Delayed MET calls occurred in 50% of patients with the MET syndrome of respiratory distress and in 39% of those with hypotension ( P = .11). The median duration of delay was 12 hours in patients with respiratory distress compared to 5 hours for patients with hypotension ( P = .016). A delay in making a MET call was associated with an increase in mortality (odds ratio, 2.10; 95% confidence interval, 1.01-4.34; P = .045). Conclusions Patients receiving MET calls for respiratory distress or hypotension were elderly and had a mortality greater than 35%. In many cases, MET activation was delayed. This delay was associated with increased mortality.

Protein C Concentrations Correlate With Organ Dysfunction and Predict Outcome Independent of the Presence of Sepsis

Protein C Concentrations Correlate With Organ Dysfunction and Predict Outcome Independent of the Presence of Sepsis

Characteristics and outcomes of patients receiving a medical emergency team review for acute change in conscious state or arrhythmias*

To describe the characteristics and outcomes of patients receiving a medical emergency team (MET) review for the MET syndromes of acute change in conscious state or arrhythmia and to assess the effect of delayed MET activation on their outcomes. Retrospective analysis of medical records. University teaching hospital. Two cohorts of 100 patients for each of the MET syndromes of acute change in conscious state or arrhythmia. None. We collected information on patient demographics, comorbidities, and presence of sepsis, hypovolemia, cardiogenic shock, and patient outcome. We also documented the presence and duration of delayed MET activation. The median age for both syndromes was >70 yrs, and major comorbidities were present in >10% of patients. A history of ischemic heart disease (p < .001) and congestive cardiac failure (p = .007) was more common in patients with arrhythmias. Cardiogenic shock and sepsis were common underlying causes of the MET calls for the two groups. However, cardiogenic shock was more common in patients with arrhythmias (p < .001). Hospital mortality was 35% for patients with an acute change in conscious state, compared with 18% for patients with arrhythmias (p = .01). Delayed MET activation occurred in 35% of acute change in conscious state patients and in 24% of arrhythmia patients (p = .09) with a median duration of delay of 16 and 13 hrs, respectively. Delayed MET activation was associated with increased mortality (odds ratio 3.1, 95% confidence interval 1.4-6.6, p = .005). An acute change in conscious state leading to a MET call carried a greater risk of death than activation due to arrhythmias. Delayed activation was common for both syndromes and was independently associated with an increased risk of death.

Autopsy cases of fulminant‐type bacterial infection with necrotizing fasciitis: Group A (beta) hemolytic Streptococcus pyogenes versus Vibrio vulnificus infection

Two autopsy cases of fulminant-type infection associated with necrotizing fasciitis were analyzed clinicopathologically. Both cases involved 57-year-old alcohol abusers. The former was a woman with group A (beta) hemolytic Streptococcus pyogenes infection, and the latter was a man with Vibrio vulnificus infection. The sudden onset of shock with high fever resulted in sepsis, decreased clotting, and hepatorenal symptoms, followed by death within a few days. Post-mortem examination showed widespread congestion and bleeding, and alcoholic liver cirrhosis was observed. Necrotizing fasciitis was identified in both cases. Bacteria from the pharynx or intestinal tract invaded the blood, and marked bacterial proliferation produced sepsis, resulting in necrotizing fasciitis. Despite the presence of sepsis, bilateral pulmonary congestion and bleeding were observed without pneumonia. Due to the rapid progression of sepsis, there was no time for granulocyte migration from the bone marrow. It seems that almost all mature granulocytes which had already existed in the bone marrow accumulated at the focus of necrotizing fasciitis because the bone marrow had few mature granulocytes and lacked hypercellularity. The cause of death in each case was circulatory collapse due to septic shock. It was difficult to distinguish the type of infection on histopathology. Cultures were necessary to determine the bacterial agents involved.

Sustained low-efficiency daily dialysis with hemofiltration for acute kidney injury in the presence of sepsis

Acute kidney injury (AKI) commonly occurs in critically ill patients with sepsis and is associated with poor outcomes. Unfortunately, the ideal mode of renal replacement therapy remains unknown. Because both higher doses of dialysis and hemofiltration have been associated with improved survival, we postulated that adding hemofiltration to the diffusive clearance achieved by sustained low-efficiency daily dialysis (SLEDD-f) would provide a survival advantage over SLEDD. From December 2003 to October 2005, we retrospectively analyzed all patients with multisystem organ failure, vasopressor-dependent hypotension and oliguric acute kidney failure secondary to nonoperative sepsis who were treated with renal replacement therapy (RRT). After exclusionary criteria were applied, 8 patients received SLEDD-f and 13 patients received SLEDD. All treatments were for 8 - 16 h/day. SLEDD-f was continued until vasopressors were reduced to a minimal dose. Outcomes were mortality and recovery of renal function at 30 days after initiation of RRT. APACHE- II scores were calculated at the time of dialysis initiation to predict mortality. Despite higher APACHE II scores, 30-day survival was 100% in the SLEDD-f group and 38% in the SLEDD group. Furthermore, most of the SLEDD-f patients were able to have vasopressors weaned quickly and all patients in the SLEDD-f group recovered significant renal function to allow discontinuation of RRT. While the optimal treatment remains unknown, this small study raises the possibility that SLEDD-f offers a survival advantage and increases the chance of renal recovery while decreasing the need for vasopressors. A large randomized trial comparing SLEDD-f with other forms of renal replacement therapy is needed.

Plasma bilirubin correlations in non-obstructive cholestasis after partial hepatectomy

The aim of this study was to provide an improved outline of the patterns and correlates of changes in plasma bilirubin after partial hepatectomy. A large series of blood measurements and complementary variables were prospectively collected from 85 patients undergoing liver resection, and bilirubin correlations were assessed by regression analysis. Early postoperatively, the best simultaneous correlates of increasing bilirubin were the preoperative value, the duration of surgery, and the number of blood transfusions (r2 = 0.74, p < 0.001). Subsequently, increasing bilirubin became related to the number of resected liver segments, the duration of intraoperative liver ischemia, the use of continuous vs. intermittent ischemia, and the presence of sepsis (r2 = 0.82, p < 0.001); these were also the best simultaneous correlates of peak bilirubin. This pattern was characterized by prominently conjugated hyperbilirubinemia, hypocholesterolemia, and moderately increased alkaline phosphatase, and occurred in the absence of obstructive cholestasis. Major hepatectomy, parenchymal ischemia, and sepsis have similar and synergistic impacts as determinants of prominently conjugated hyperbilirubinemia after liver resection. This is likely related to impaired hepatocellular bilirubin transport and occurs in the absence of obstructive components.

Outcome of totally implantable venous access device-related bacteraemia without device removal

The optimal management of bacteraemia related to the presence of totally implantable venous access devices (TIVADs) remains controversial, particularly in terms of whether to remove the infected catheter. The objective of this study was to determine the factors associated with success or failure of treatment of TIVAD-related bacteraemia in patients from whom the infected device was not removed. The outcome of 92 episodes of TIVAD-related bacteraemia and the factors predictive of an unfavourable outcome were evaluated retrospectively. In 32 (35%) episodes, the devices were removed immediately. In 60 episodes, patients were treated with antibiotics infused through the device; treatment was successful in 56% of these cases (66% for infections caused by coagulase-negative staphylococci). Only the presence of sepsis (OR 9.42, 95% CI 1.29-68.92, p 0.0271) and of local signs of infection (OR 9.61, 95% CI 1.98-46.49, p 0.0049) independently predicted the failure of catheter-retaining treatment. Finally, only one-third of the devices were retained. In conclusion, the large number of TIVADs that are removed because of infection justifies reconsidering the criteria for device removal. During catheter-retaining treatment, the presence of local signs of infection or reported sepsis were independent factors for reduced probability of retaining the device.

Scottish Foot Ulcer Risk Score Predicts Foot Ulcer Healing in a Regional Specialist Foot Clinic

To determine whether patients developing ulcers had previously been identified as being at high risk of ulceration using the Scottish Care Information-Diabetes Collaboration (SCI-DC) ulcer risk score and whether the risk score predicts ulcer healing. All patients attending the diabetes foot clinic with an ulcer had been assessed for foot ulcer risk using the SCI-DC risk calculator, which categorizes patients into low, moderate, or high risk of ulceration. Information on foot pulses, neuropathy, foot deformity, previous ulcer, ulcer site, depth, and presence of sepsis was recorded and related to ulcer outcome. Patients were followed up until outcome was achieved (median 3 months [range 1-33]). Of patients attending the clinic with a foot ulcer (mean [+/-SD] age 67.3 +/- 12.7 years, 68% male), 68% were previously recognized to be at high risk of foot ulceration, and 98% were high or moderate risk. Of 221 ulcers, the healing rate was 75% overall but was lower for high-risk patients compared with other patients (68 vs. 93%; P < 0.0001). Of the remainder, 3% became chronic ulcers, 12% required minor or major amputation, and 10% died with their ulcer. In multivariate analysis, absent pulses, neuropathy, increased age, and deep ulcers were associated with poor healing. The combination of neuropathy and ischemia was particularly associated with poor outcome of an ulcer (61% healing). The Scottish foot ulcer risk score predicts both ulcer development and ulcer healing. The risk score can be a useful initial guide to determine the likelihood of poor healing. The individual criteria contributing to this overall risk are similar to other studies.

Cytokine Profiles of Peripheral Blood Mononuclear Cells Isolated from Septic and Healthy Neonatal Foals

Background:Septicemia initiates the production of pro‐inflammatory (interleukin [IL] 1‐beta [IL‐β], interferon‐gamma [IFN‐γ], IL‐6), and anti‐inflammatory (IL‐4) cytokines. The transcription of some of these proteins (IL‐8, IL‐6) is linked to endotoxin‐induced activation of the toll‐like receptor 4 (TLR4) on peripheral blood mononuclear cells (PBMC).Hypotheses: Septic foals fail to increase gene expression of IFN‐γ. Nonsurviving septic foals exhibit distinctive cytokine profiles.Animals:Twenty‐one septic and 20 healthy neonatal foals.Methods:Using real‐time polymerase chain reaction, gene expression of IFN‐γ, IL‐1β, IL‐6, IL‐4, IL‐8, TLR4, and β‐actin in PBMC were measured in samples obtained from septic foals at 0, 24, and 72 hours (T = 0, 24, and 72 hours) after admission to the Cornell University Hospital for Animals. Control foals were sampled at comparable times.Results:At T = 0 hours, septic foals exhibited a 6‐fold decrease in gene expression of IL‐4 and a 5‐fold increase in gene expression of TLR4. Gene expression of IFN‐γ, IL‐6, IL‐8, or of IL‐1β did not differ between the 2 groups of foals at T = 0 hours. In septic foals that died (n = 3), there was a 15‐fold increase in IL‐6 at T = 0 hours compared to survivors.Conclusions and Clinical Importance: Septic foals, unlike septic human infants, up‐regulate TLR4 gene expression, which may enhance pro‐inflammatory cytokine production. Despite the presence of sepsis, IFN‐γ was not up‐regulated. Additional studies are needed to verify that increased IL‐6 expression is associated with a poor prognosis in septic foals.

Effects of hydroxyethyl starch administration on renal function in critically ill patients

The influence of hydroxyethyl starch (HES) solutions on renal function is controversial. We investigated the effect of HES administration on renal function in critically ill patients enrolled in a large multicentre observational European study. All adult patients admitted to the 198 participating intensive care units (ICUs) during a 15-day period were enrolled. Prospectively collected data included daily fluid administration, urine output, sequential organ failure assessment (SOFA) score, serum creatinine levels, and the need for renal replacement therapy (RRT) during the ICU stay. Of 3147 patients, 1075 (34%) received HES. Patients who received HES were older [mean (SD): 62 (SD 17) vs 60 (18) years, P = 0.022], more likely to be surgical admissions, had a higher incidence of haematological malignancy and heart failure, higher SAPS II [40.0 (17.0) vs 34.7 (16.9), P < 0.001] and SOFA [6.2 (3.7) vs 5.0 (3.9), P < 0.001] scores, and less likely to be receiving RRT (2 vs 4%, P < 0.001) than those who did not receive HES. The renal SOFA score increased significantly over the ICU stay independent of the type of fluid administered. Although more patients who received HES needed RRT than non-HES patients (11 vs 9%, P = 0.006), HES administration was not associated with an increased risk for subsequent RRT in a multivariable analysis [odds ratio (OR): 0.417, 95% confidence interval (CI): 0.05-3.27, P = 0.406]. Sepsis (OR: 2.03, 95% CI: 1.37-3.02, P < 0.001), cardiovascular failure (OR: 6.88, 95% CI: 4.49-10.56, P < 0.001), haematological cancer (OR: 2.83, 95% CI: 1.28-6.25, P = 0.01), and baseline renal SOFA scores > 1 (P < 0.01 for renal SOFA 2, 3, and 4 with renal SOFA = 0 as a reference) were all associated with a higher need for RRT. In this observational study, haematological cancer, the presence of sepsis, cardiovascular failure, and baseline renal function as assessed by the SOFA score were independent risk factors for the subsequent need for RRT in the ICU. The administration of HES had no influence on renal function or the need for RRT in the ICU.

Cytokine Profiles of Peripheral Blood Mononuclear Cells Isolated from Septic and Healthy Neonatal Foals

Septicemia initiates the production of pro-inflammatory (interleukin [IL] 1-beta [IL-1beta], interferon-gamma [IFN-gamma], IL-6), and anti-inflammatory (IL-4) cytokines. The transcription of some of these proteins (IL-8, IL-6) is linked to endotoxin-induced activation of the toll-like receptor 4 (TLR4) on peripheral blood mononuclear cells (PBMC). Septic foals fail to increase gene expression of IFN-gamma. Nonsurviving septic foals exhibit distinctive cytokine profiles. Twenty-one septic and 20 healthy neonatal foals. Using real-time polymerase chain reaction, gene expression of IFN-gamma, IL-1beta, IL-6, IL-4, IL-8, TLR4, and beta-actin in PBMC were measured in samples obtained from septic foals at 0, 24, and 72 hours (T = 0, 24, and 72 hours) after admission to the Cornell University Hospital for Animals. Control foals were sampled at comparable times. At T=0 hours, septic foals exhibited a 6-fold decrease in gene expression of IL-4 and a 5-fold increase in gene expression of TLR4. Gene expression of IFN-gamma, IL-6, IL-8, or of IL-1beta did not differ between the 2 groups of foals at T = 0 hours. In septic foals that died (n = 3), there was a 15-fold increase in IL-6 at T = 0 hours compared to survivors. Septic foals, unlike septic human infants, up-regulate TLR4 gene expression, which may enhance pro-inflammatory cytokine production. Despite the presence of sepsis, IFN-gamma was not up-regulated. Additional studies are needed to verify that increased IL-6 expression is associated with a poor prognosis in septic foals.

NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure

Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro- and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position +242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position -262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity. Genomic DNA was extracted from peripheral blood leukocytes and analyzed with a restriction fragment length polymorphism PCR method. Genotype-phenotype associations were characterized by measuring circulating nitrotyrosine and catalase activity. Observed and expected genotype frequencies were not significantly different, and overall baseline characteristics were not significantly different according to the various genotype groups. A genotype-phenotype association was demonstrable between the NADPH oxidase p22phox genotypes and plasma nitrotyrosine level (P = 0.06), as well as between the catalase genotypes and whole-blood catalase activity (P < 0.001). Compared with the NADPH oxidase p22phox CC genotype group, the T-allele group had a higher cumulative probability of remaining hospitalized (P = 0.03). Compared with the NADPH oxidase p22phox CC genotype, the T-allele carrier state was associated with 2.1-fold higher odds for dialysis requirement or hospital death (P = 0.01). This association persisted with 2.0- to 2.2-fold higher odds for this composite outcome after adjustment for race; gender; age; and the Acute Physiology and Chronic Health Evaluation II score (P = 0.03), the Multiple Organ Failure score (P = 0.01), or presence of sepsis (P = 0.02). The polymorphism in the gene that encodes the NADPH oxidase p22phox subunit at position +242 is associated with dialysis requirement or hospital death among patients with ARF. Larger studies are needed to confirm these relationships.

The effects of saline or albumin resuscitation on acid-base status and serum electrolytes*

To test whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in acid-base status and serum electrolytes. Nested cohort study. Three general intensive care units. Six hundred and ninety-one critically ill patients. Randomization of patients to receive blinded solutions of either 4% human albumin or normal saline for fluid resuscitation. Albumin was given to 339 patients and saline to 352. At baseline, both groups had a similar serum bicarbonate, albumin, and base excess levels. After randomization, bicarbonate and base excess increased significantly and similarly over time (p < .0001). On multivariate analysis, fluid resuscitation with albumin predicted a smaller increase in pH (p = .0051), bicarbonate (p = .034), and base excess (p = .015). The amount of fluid was an independent predictor of pH (p < .0001), serum chloride (p < .0001), calcium (p = .0001), bicarbonate (p = .0002), and base excess (p < .0001) on the first day of treatment. In patients who received >3 L of fluids in the first 24 hrs, albumin administration was associated with a significantly greater increase in serum chloride (p = .0026). Acute Physiology and Chronic Health Evaluation II score and the presence of sepsis also independently predicted changes in several electrolytes and acid-base variables. When comparing albumin and saline, the choice and amount of resuscitation fluid are independent predictors of acid-base status and serum electrolytes. When large volumes are given, albumin administration leads to a higher chloride concentration. However, overall differences between the types of fluid are minor, whereas the volume of fluid administered is a much stronger predictor of such changes, which are also influenced by illness severity and the passage of time.

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study

BackgroundA low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood.MethodsWe examined the relation between CSF WBC, bacteraemia and sepsis in a prospective cohort study that included 352 episodes of pneumococcal meningitis, confirmed by CSF culture, occurring in patients aged >16 years.ResultsCSF WBC was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm3 (interquartile range 531–6983 per mm3) and 104 patients (33%) had a CSF WBC <1000/mm3. Patients with a CSF WBC <1000/mm3 were more likely to have an unfavourable outcome (defined as a Glasgow Outcome Scale score of 1–4) than those with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was significantly associated with blood WBC (Spearman's test 0.29), CSF protein level (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C-reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm3 more often had a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more often developed systemic complications (cardiorespiratory failure, sepsis) than those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22, 95%CI 1.02–1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17–5.14), and a low thrombocyte count on admission (Odds ratio per 100,000/mm3 increments 0.67, 95% CI 0.47–0.97) were associated with a CSF WBC <1000/mm3.ConclusionA low CSF WBC in adults with pneumococcal meningitis is related to the presence of signs of sepsis and systemic complications. Invasive pneumococcal infections should possibly be regarded as a continuum from meningitis to sepsis.

Some aspects of long-term results of treatment of acute hematogenous osteomyelitis

The aim of the study was to evaluate the treatment results of acute hematogenous osteomyelitis over 10 years and to determine the relationship between them and clinical course of the disease. The patients with acute hematogenous osteomyelitis diagnosed 10 years ago (1995-1996) were enrolled in the study. The post mail or phone contacts with them or their parents were obtained, the questions were submitted, and the patients were invited for medical examination. The current complaints and limitations in physical activity were assessed. The amplitude of joint movements, tenderness during palpation, and deformations were evaluated during physical examination. Patients were divided into two groups: with and without complaints. The duration and severity of the disease, age, gender, presence of sepsis, arthritis, and subperiosteal abscess, the type of bone affected and bone lesion on x-ray, duration of fever, and maximal erythrocyte sedimentation rate during the acute period were compared between groups. We made 50 phone calls and sent seven letters to the patients with acute hematogenous osteomyelitis who were treated in our department. In 14 (28%) cases, phone contact was obtained, and 7 of them were examined. Five answers (71%) to the letters were received. The overall response rate was 33%. Thirteen (68%) former patients had no any complaints; six (32%) had minor complaints, which were probably linked to acute hematogenous osteomyelitis. Fifteen (79%) former patients had no limitations in any physical activities, and four (21%) of them limit their physical activities. Seven patients were examined, but neither visible deformities and tenderness nor limitations in movement amplitude were found. Comparing the groups with complaints and without complaints by age, gender, presence of sepsis and arthritis, duration of the disease, and the presence of periosteal abscess, no statistically significant difference in any of variables was found. According to our data, 37% of the patients have complaints 10 years after acute hematogenous osteomyelitis, and these complaints are not associated with the clinical course of the disease.

Fournier’s Gangrene: Risk Factors and Strategies for Management

The prognosis of Fournier's gangrene (FG) depends on early diagnosis and management. In this study, our objective was to identify the distinct features of FG that may influence the clinical outcome. A retrospective chart review was performed in patients with a diagnosis of FG between January 1999 and December 2003. Etiological and predisposing factors, causative microbiological organisms, and clinical outcome were investigated. Twenty-five men (71%) and 10 women (29%) were included in the study. Mean age was 59.7 +/- 10.7 (range: 43-88) years. As a predisposing factor, diabetes mellitus (DM) was found to be in 46% of patients. All patients were treated by immediate debridement and wide-spectrum antibiotics. More than one bacterium was found in 75% of the patients' tissue cultures, and most frequently E. coli (43%) was identified. Although there were no etiological factors in 25 patients (71%), various etiological factors were found in 10 patients (29%). Multiple debridements were performed in the majority of the cases. The overall mortality rate was 40%. The mortality rates were found to be relatively higher in patients with diabetes mellitus (DM; 50%), with delayed admission to the hospital (45%), and in patients presenting with sepsis at the first admission to the hospital (78%) compared with others. In the logistic regression model, the presence of sepsis was as the only significant independent risk factor for mortality in FG. Despite the use of contemporary effective antibiotic treatment, aggressive debridements, and state-of-the-art intensive care conditions, FG still has high mortality and morbidity rates. In our series mortality rates were found to be higher in patients with delayed admission to the hospital, those with DM, and those who initially presented with sepsis.

Death Certificates Are Not Reliable: Revivification of the Autopsy

Medicine assumes that vital statistics are accurate, but they are only as good as the death certificates. To evaluate the accuracy of death certificates in reporting vital statistics with an emphasis on cardiac deaths. A population-based retrospective study within one community hospital. During the study period, 1,619 patients expired during hospitalization, of which 223 underwent autopsy. Clinical diagnoses were determined from the death certificate and autopsy results from the final pathology reports. Concordance of myocardial infarction as the underlying cause of death between the death certificate and the autopsy was measured. New diagnoses uncovered by the autopsy were tabulated. The death certificate missed acute myocardial infarction in 25 of 52 autopsy-proven cases (48% errors of omission). Conversely, it erroneously asserted the presence of an acute myocardial infarction in 9/36 cases (25% errors of commission). Autopsy showed these nine cases actually were pneumonia (5), sepsis with ARDS (2), cerebral hemorrhage (1), and cardiac tamponade (1). Autopsy proved 52 myocardial infarctions causing death, while death certificates accurately reported only 27. Myocardial infarction was more likely to be unsuspected in extreme ages, in women, when found in right ventricle or posterior wall, and in the presence of sepsis or ARDS. Death certificates were frequently inaccurate and in 21.5% of cases were of no value because of an inadequate diagnosis, ie, cardiopulmonary arrest, arrhythmia or respiratory failure. Major discrepancies of commission and omission occur frequently between the death certificate and autopsy. 1) Death certificates are often wrong. 2) The time-honored autopsy is more valuable than ever. 3) Physicians need to write better death certificates and correct them. 4) Death certificate-based vital statistics should be corrected with autopsy results. 5) Vital statistics should note deaths confirmed by autopsy. 6) More autopsies would improve vital statistics and the practice of medicine.

Molecular Pathology: Future Issues

The field of molecular pathology is expanding in complexity. To achieve competency, vigilance is required. To review the advances in clinically useful molecular biologic techniques and to identify their applications in clinical practice, as presented at the 13th Annual William Beaumont Hospital DNA Symposium. The 4 manuscripts submitted were reviewed and their major findings were compared with the literature on the same or related topics. Manuscripts address the use of molecular or immunophenotyping by flow cytometry to evaluate the origin or presence of sepsis, respectively; the use of imatinib mesylate to treat chronic myeloid leukemia and the nature of resistance to imatinib; and the use of 9 and 10 fluorochromes during clinical flow cytometric studies. The epidemiologic evaluation of a septic outbreak may be monitored using molecular techniques that track the relatedness of isolates. A potential biomarker for the presence of early sepsis is CD64. Intracellular signal transduction pathways are altered in malignancy. Imatinib mesylate inhibits the BCR-ABL kinase created by translocation of the long arms of chromosomes 9 and 22 in chronic myeloid leukemia. Resistance to imatinib may be secondary to mutation in the BCR-ABL kinase domain or residual leukemic stem cells that imatinib does not kill. The use of 9 or 10 fluorochromes simultaneously during flow cytometry has many clinical advantages; however, software for data analysis is needed. The current postgenomic era will continue to emphasize the use of microarrays and database software for genomic, transcriptomic, proteomic, nutrigenomic, and pharmacogenomics screening to search for a useful clinical assay. The number of molecular pathologic techniques will expand as additional disease-associated mutations are defined.