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Biomedical subjects

Peter Nightingale

Publications and source records attributed to Peter Nightingale.

17 recordsLinked to original sources

Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation?

The Banff schema incorporates a semiquantitative scoring system for grading of acute cellular rejection (ACR) of the liver allograft. The Banff rejection activity index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation (E); bile duct damage (B); and portal inflammation (P); the scores are combined to an overall score (the RAI). The purpose of this research was to determine the prognostic value of the Banff RAI score in predicting the response to increased immunosuppression and the long-term outcome of the graft. A retrospective study was done of patients undergoing primary liver transplantation between January 2000 and October 2004 with tacrolimus-based immunosuppression; 495 patients were included, 231 had histologically-confirmed ACR, 193 responded to 1 cycle of high-dose steroids. There was no correlation between the total RAI score and response to steroids, resistant rejection, development of chronic rejection, or graft survival. The E score was related to patient survival, a lower score being associated with a worse outcome (P = 0.048). In multivariable analysis, serum bilirubin, serum aspartate aminotransferase, and E score were significant predictors of death (P = 0.012). In univariable analysis, B score and bilirubin were significantly related to "resistant rejection" (P = 0.018 and 0.002, respectively), but only bilirubin was significant in multivariable analysis (logistic regression). In conclusion, although the Banff RAI score is a useful marker of the severity of rejection, neither the total RAI score nor any of the individual components correlated with response to steroids or graft survival.

Adolescent↗

Improved myocardial protection during coronary artery surgery with glucose-insulin-potassium: a randomized controlled trial.

OBJECTIVE: We sought to assess the role of glucose-insulin-potassium in providing myocardial protection in nondiabetic patients undergoing coronary artery surgery with cardiopulmonary bypass. METHODS: A prospective, randomized, double-blind, placebo-controlled trial was conducted at a single-center university hospital performing adult cardiac surgery. Two hundred eighty nondiabetic adult patients undergoing first-time elective or urgent isolated multivessel coronary artery bypass grafting were prospectively randomized to receive glucose-insulin-potassium infusion or placebo (dextrose 5%) before, during, and for 6 hours after surgical intervention. Anesthetic, cardiopulmonary bypass, myocardial protection, and surgical techniques were standardized. The primary end point was postreperfusion cardiac index. Secondary end points were systemic vascular resistance index, the incidence of low cardiac output episodes, inotrope and vasoconstrictor use, and biochemical-electrocardiographic evidence of myocardial injury. The incidence of dysrhythmias and infections requiring treatment was recorded prospectively. RESULTS: The glucose-insulin-potassium group experienced higher cardiac indices (P < .001) throughout infusion and reduced vascular resistance (P < .001). The incidence of low cardiac output episodes was 15.9% (22/138) in the glucose-insulin-potassium group and 27.5% (39/142) in the placebo group (P = .021). Inotropes were required in 18.8% (26/138) of the glucose-insulin-potassium group and 40.8% (58/142) of the placebo group (P < .001). Fewer patients in the glucose-insulin-potassium group (12.3% [16/133]) versus those in the placebo group (23.4% [32/137]) had significant myocardial injury (P = .017). Noncardiac morbidity was not different. CONCLUSION: Glucose-insulin-potassium therapy improves early postoperative cardiovascular performance, reduces inotrope requirement, and might reduce myocardial injury. These potential benefits are not at the expense of increased noncardiac morbidity.

Cardiomyopathies↗

Microalbuminuria in the intensive care unit: Clinical correlates and association with outcomes in 431 patients.

OBJECTIVE: Comparison of urine albumin within 6 hrs of intensive care unit (ICU) admission with demography, clinical classification, outcome, inotrope/vasopressor requirement, clinical assessment of mortality risk, and Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. DESIGN: Urine albumin-creatinine ratio (ACR) was measured on ICU admission (ACR 1) and after 4-6 hrs (ACR 2). SETTING: A 17-bed general ICU in a university teaching hospital. PATIENTS: Unselected medical (206) and surgical (225) patients recruited prospectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Bedside urine ACR was measured by nurses using a Bayer DCA 2000 analyzer and expressed in mg/mmol (reference range <2.3). ACR 1 in medical and surgical patients was 15.5 (12.4-19.5) and 8.2 (5.9-11.1) mg/mmol, respectively (p = .0002), and ACR 2 was 9.0 (5.8-12.5) and 4.6 (3.6-5.3), respectively (p < .0001). For all patients, median (95% confidence interval) ACR fell from 11.2 (8.7-13.2) to 5.4 (4.7-6.8) mg/mmol 4-6 hrs after ICU admission (p < .0001). ACR 1 for nonsurvivors (n = 90) and survivors (n = 341) was 16.1 (11.2-21.3) and 8.8 (6.9-11.9), respectively (p = .0002) and ACR 2, 12.4 (8.2-18.9) and 4.8 (3.9-5.4), respectively (p < .0001). In both medical and surgical patients who died on the ICU, median ACR failed to decrease significantly following admission. ACR1 and ACR 2 were higher in patients who required inotropic or vasopressor support and correlated with duration of therapy. ACR 1 and 2 were inversely correlated with mean Po2/Fio2 ratio 48 hrs after ICU admission and positively correlated with duration of mechanical ventilation and ACR 1 with ICU stay. ACR 2 predicted mortality and ACR 1 inotrope requirement independent of clinical mortality risk assessment and APACHE II and SOFA scores. CONCLUSIONS: Urine albumin changes rapidly within the first 6 hrs following ICU admission and predicts ICU mortality and inotrope requirement as well as or better than APACHE II and SOFA scores. Serial urine albumin measurement may provide a means of monitoring the microvascular effects of systemic inflammation.

APACHE↗

Results of combination treatment with pegylated interferon and ribavirin in cirrhotic patients with hepatitis C infection.

BACKGROUND: The treatment of hepatitis C patients with advanced cirrhotic liver disease remains challenging and data on the outcome of treatment for this patient group is limited. RESULTS: Between September 2000 and August 2004, 61 cirrhotic patients started treatment with pegylated interferon and ribavirin (42 male, age range 29-69 years, 26 Asian). Forty-three (70%) patients were serum hepatitis C virus (HCV) RNA negative at the end of treatment and 24 (39%) achieved a sustained virological response (SVR). SVR was achieved for 35% (6/17) of patients with genotype 1, and for 39% (16/41) with genotype 3. Caucasians with genotype 3 demonstrated a higher cure rate (SVR 10/18 = 56%) than Asians (SVR 6/24 = 25%). Failure to achieve SVR was associated with lower platelet count, neutrophil count and albumin at baseline. Twenty patients suffered clinical or laboratory decompensation, five patients required hospitalization, and two patients died. Patients who experienced hepatic decompensation were older and had baseline characteristics associated with more advanced liver disease. CONCLUSION: The treatment of patients with advanced HCV is challenging, although many treated patients achieve SVR. Significant toxicity is experienced and there is treatment-related mortality. This balance of efficacy and toxicity needs to be considered before commencing treatment.

Adult↗

Nutritional markers in liver allograft recipients.

BACKGROUND: Malnutrition is common in patients with end-stage liver disease considered for transplantation, but it is unclear whether this affects the outcome after transplantation. AIM.: To determine whether the severity of malnutrition in liver transplant candidates affects outcome after transplantation. METHODS: We did a prospective study of 61 patients with chronic liver disease accepted for transplantation. FINDINGS: The Child-Pugh and Model for End-Stage Liver Disease (MELD) score correlated significantly but weakly with the mid-arm circumference (MAC) (rho=-0.34 and -0.31, P=0.015 and 0.025, respectively) but not with hand-grip strength, triceps skin-fold thickness (TSFT), or mid-arm muscle circumference. The Child-Pugh score but not the MELD was significantly associated with intensive therapy unit stay but not eventual outcome; there was a weak but statistically significant correlation between death and MAC (rho=+0.29, P=0.04) and TSFT (rho=+0.25, P=0.02). CONCLUSIONS: These findings suggest that nutritional parameters and markers of disease severity do not correlate well with outcomes after transplantation.

Adult↗

Blood lactate but not serum phosphate levels can predict patient outcome in fulminant hepatic failure.

Early identification of those patients with fulminant hepatic liver failure (FHF) who need a transplant greatly helps in their management. A number of prognostic criteria have recently been proposed, including arterial blood lactate and serum phosphate concentrations. To validate their use, we retrospectively studied 83 consecutive patients with FHF admitted to our intensive treatment unit between August 2000 and March 2003. A total of 48 patients (58%) survived with medical management only (group I) and 35 patients (42%) failed to survive spontaneously (group II). This group included 19 patients (23%) who underwent orthotopic liver transplantation (LT), and 16 patients (19%) who died without undergoing LT (group IIa). A total of 5 patients (6%) who underwent liver transplantation died. Within paracetamol overdose (POD) and non-POD subgroups, phosphate concentrations were not significantly higher in group II patients (P = 0.08 and P = 0.27, respectively), when compared to group I patients. In multivariate analysis, post admission 12-hour lactate level was the only predictor of survival for the POD subgroup, whereas in non-POD patients, 12-hour lactate and admission bilirubin levels were significant in predicting patients' outcome. In conclusion, we found that while serum phosphate concentrations have limited clinical utility as prognostic markers, persistently elevated arterial blood lactate levels despite adequate fluid resuscitation are indicators of a poor prognosis in FHF.

Adult↗

Outcome of mechanically ventilated patients who require a tracheostomy.

OBJECTIVE: To estimate the prevalence of, the risk factors associated with, and the outcome of tracheostomy in a heterogeneous population of mechanically ventilated patients. DESIGN: Prospective, observational cohort study. SETTING: A total of 361 intensive care units from 12 countries. PATIENTS: A cohort of 5,081 patients mechanically ventilated for >12 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 546 patients (10.7%) had a tracheostomy during their stay in the intensive care unit. Tracheostomy was performed at a median time of 12 days (interquartile range, 7-17) from the beginning of mechanical ventilation. Variables associated with the performance of tracheostomy were duration of mechanical ventilation, need for reintubation, and neurologic disease as the primary reason of mechanical ventilation. The intensive care unit stay of patients with or without tracheostomy was a median of 21 days (interquartile range, 12-32) vs. 7 days (interquartile range, 4-12; p < .001), respectively, and the hospital stay was a median 36 days (interquartile range, 23-53) vs. 15 days (interquartile range, 8-26; p < .001), respectively. Adjusting by other variables, tracheostomy was independently related with survival in the intensive care unit (odds ratio, 2.22; 95% confidence interval, 1.72-2.86). Mortality in the hospital was similar in both groups (39% vs. 40%, p = .65). CONCLUSIONS: Tracheostomy is a common surgical procedure in the intensive care unit that is associated with a lower mortality in the unit but with a longer stay and a similar mortality in the hospital than in patients without tracheostomy.

Cohort Studies↗

Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis.

OBJECTIVE: To study the prognostic value of antibodies to cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF), alone and in combination, in patients with very early synovitis. METHODS: A cross-sectional study was performed in patients with established inflammatory and noninflammatory disease to validate the assay in our unit and confirm previously reported sensitivities and specificities of anti-CCP antibodies. Subsequently, patients with synovitis of 3 months' duration were followed for 72 weeks and the ability of anti-CCP antibodies and RF to predict the development of rheumatoid arthritis (RA) and persistent inflammatory arthritis was assessed. RESULTS: One hundred twenty-four patients were assessed in the initial cross-sectional study. Anti-CCP antibodies and RF were detected by ELISA in only 4% of patients with non-RA inflammatory disease and in no patient with noninflammatory disease. Ninety-six patients with very early synovitis were assessed longitudinally. In these patients with early arthritis, the combination of anti-CCP antibodies and RF had a specificity, positive predictive value (PPV), sensitivity, and negative predictive value (NPV) for a diagnosis of RA of 100%, 100%, 58%, and 88%, respectively. The specificity, PPV, sensitivity, and NPV of this antibody combination for the development of persistent disease-fulfilling classification criteria for RA were 97%, 86%, 63%, and 91%, respectively. CONCLUSION: In patients with synovitis of 3 months' duration, a combination of anti-CCP antibodies and RF has a high specificity and PPV for the development of persistent RA. This autoantibody combination can be used to identify patients with disease destined to develop RA who may be appropriate for very early intervention.

Adult↗

Low density lipoprotein apolipoprotein B metabolism in treatment-naive HIV patients and patients on antiretroviral therapy.

BACKGROUND: Dyslipidaemia and lipodystrophy have been described in treated HIV patients and in a small percentage of untreated HIV patients. Lipodystrophy in these patients has been shown to be associated with a lower expression of low density lipoprotein (LDL) receptors. METHODS: We have investigated the effect of antiretroviral treatment with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) on body fat distribution and LDL apolipoprotein B (apoB) kinetics in 12 HIV-negative controls and 52 HIV-infected patients, including antiretroviral treatment-naive (TN) patients (n=13) and patients taking two nucleoside analogues plus either a PI (n=15) or an NNRTI (n=24). RESULTS: LDL cholesterol was not different between groups. Compared with the controls, LDL apoB absolute synthetic rate (ASR) and fractional catabolic rate (FCR) were lower and residence time (RT) was higher in the PI and NNRTI groups (P<0.05). In the TN patients, LDL ASR was lower (P<0.05) and there was a trend for a lower FCR and higher RT compared with the controls (P=0.07). LDL apoB pool size was greater in the PI group compared with the controls (P<0.05). In the PI group, patients on ritonavir (RTV)-containing regimens had a lower LDL apoB ASR (P=0.009) and a trend to a lower LDL apoB FCR and increased RT compared with non-RTV-containing PI regimens (P=0.05). There was a positive correlation between LDL apoB FCR and limb fat/lean body mass (P=0.004) in all subjects. CONCLUSIONS: Decreased LDL FCR, despite unchanged LDL cholesterol, was demonstrated in both treated and untreated HIV patients. It was more marked with RTV-containing regimens and was associated with reduced limb fat. The increased LDL RT may lead to an increased risk of atherogenesis thus contributing to the risk for cardiovascular disease in these patients.

Adult↗

Antiretroviral treatment reduces very-low-density lipoprotein and intermediate-density lipoprotein apolipoprotein B fractional catabolic rate in human immunodeficiency virus-infected patients with mild dyslipidemia.

The relationship between antiretroviral treatment of HIV infection, body fat distribution, insulin resistance, and very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) apolipoprotein-B (apoB) kinetics was investigated in 55 HIV-infected patients taking two nucleoside analogs plus either a protease inhibitor (n = 15) or a nonnucleoside reverse transcriptase inhibitor (n = 25), 15 antiretroviral therapy-naive patients, and 12 HIV-negative controls. Compared with the controls, high-density lipoprotein cholesterol was reduced in all groups (P < 0.01). Plasma triglyceride was increased in patients taking protease inhibitors (P < 0.05). VLDL and IDL apoB fractional catabolic rate (FCR) was lower in all treatment groups (P < 0.05) compared with controls. Trunk fat, VLDL apoB absolute secretion rate, and insulin resistance were not different between groups. Peripheral fat was lower in the treated patients (P < 0.05) and correlated with duration of therapy (r = -0.55; P < 0.001). There was a positive correlation between peripheral fat and VLDL apoB FCR (P = 0.002) and IDL apoB FCR (P = 0.002) and a negative correlation with VLDL apoB pool size, VLDL cholesterol, and triglyceride (P < 0.03; P < 0.01; P < 0.002). These results suggest that mild dyslipidemia resulting from antiretroviral therapy is caused by a decrease in VLDL and IDL apoB FCR, which is associated with a loss of peripheral fat.

Adult↗

Outcome of older patients receiving mechanical ventilation.

OBJECTIVE: To determine the threshold of age that best discriminates the survival of mechanically ventilated patients and to estimate the outcome of mechanically ventilated older patients. DESIGN: International prospective cohort study. SETTING: Three hundred sixty-one intensive care units from 20 countries. PATIENTS AND PARTICIPANTS. Five thousand one hundred eighty-three patients mechanically ventilated for more than 12 h. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Recursive partitioning and logistic regression were used and an outcome model was derived and validated using independent subgroups of the cohort. Two age thresholds (43 and 70 years) were found, by partitioning recursive analysis, to be associated with outcome. This study focuses on the analysis of patients older than 43 years of age, divided in two subgroups: between 43 and 70 years (middle age group) and older than 70 years (elderly group). Survival in hospital was 45% (95% C.I.: 43-48) for the elderly group and 55% (53-57) for the middle age group ( p<0.001). Advanced age was not associated with prolongation of mechanical ventilation, weaning or length of stay in the ICU and in hospital ( p>0.05). Variables associated with mortality in the elderly were: acute renal failure, shock, Simplified Acute Physiology Score II and a ratio of PaO(2) to FIO(2) more than 150. CONCLUSIONS: Older mechanically ventilated patients (age >70 years) had a lower ICU and hospital survival, but the duration of mechanical ventilation, ICU and hospital stay were similar to younger patients. Factors associated with the highest risk of mortality in patients older than 70 were the development of complications during the course of mechanical ventilation, such as acute renal failure and shock.

Acute Kidney Injury↗

Immunosuppression affects the rate of recurrent primary biliary cirrhosis after liver transplantation.

Identifying the risk factors associated with recurrence of primary biliary cirrhosis after liver transplantation may affect immunosuppression and increase understanding of the pathogenesis. Four hundred eighty-five patients with PBC were followed for a median of 79 months after transplantation; histological evidence of recurrence was found in 23%. On multivariate analysis, the only risk factor identified with recurrence was the type of calcineurin inhibitor used. The odds ratio for recurrence on tacrolimus was 2.73 (95% confidence interval: 1.84-4.10) compared with cyclosporine. For those receiving cyclosporine, the median time to recurrence was 123 months and for those on tacrolimus 62 months (P <.001). Reasons for this difference between the 2 calcineurin inhibitors are not clear.

Adult↗

Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) may have an increased risk of developing colorectal cancer (CRC) after liver transplantation (LT). We evaluated our patients with PSC after LT to identify risk factors for CRC and its impact on survival. PATIENTS AND METHODS: A total of 152 patients (108 men, 100 with IBD) with PSC who underwent 173 LTs between 1986 and May 2000 were analyzed in three groups: (1) PSC without IBD (n=52); (2) PSC with colectomy (pre-LT and at LT) (n=17, colectomy pre-LT in 13 and simultaneous colectomy at LT in four); and (3) PSC with IBD and an intact colon (n=83). The following factors were studied: age, gender, liver, and renal biochemistry, international normalized ratio, Child-Pugh stage, operative time, blood use, hospital stay, immunosuppression, risk of CRC, retransplantation rate, and mortality. RESULTS: The incidence of CRC after LT was 5.3% (8/152) compared with 0.6% (7/1,184) in non-PSC cases (P<0.001). All CRCs in the PSC group were in patients with IBD and an intact colon. The cumulative risk of developing CRC in the 83 patients with an intact colon and IBD was 14% and 17% after 5 and 10 years, respectively (PSC non-IBD group 0% risk after 10 years, P<0.06). The multivariate analysis showed three significant variables related to the risk of developing CRC: colonic dysplasia after LT (P<0.0003), duration of colitis more than 10 years (P<0.002), and pancolitis (P<0.004). The cause of death in patients with CRC was cancer related in 75% of cases with a reduced 5-year survival of 55% versus 75% without CRC (not significant). CONCLUSION: Patients with PSC undergoing LT with a long history of ulcerative colitis and pancolitis have an increased risk of developing CRC with reduced survival. We advocate long-term aggressive colonic surveillance and colectomy in selected high-risk patients with longstanding severe colitis.

Adolescent↗

Carriage of methicillin-resistant Staphylococcus aureus is associated with an increased risk of infection after liver transplantation.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of sepsis in patients with cirrhosis and after liver transplantation. The association between nasal carriage of MRSA and sepsis in these patients is unclear. The goal of this study was to investigate the relationship between MRSA carriage before liver transplantation and subsequent sepsis after transplantation. This was a retrospective study of 374 consecutive adults who underwent orthotopic liver transplantation between 1998 and 2001 and for whom full data were available. Of these, 157 had been screened for MRSA as part of a study assessing the prevalence of MRSA infection. All MRSA carriers were treated with nasal mupirocin and chlorhexidine baths. The records of MRSA carriers and noncarriers were analyzed for Child and Model for End-Stage Liver Disease (MELD) score, posttransplantation MRSA, and other infections and mortality. Of the 157 patients who had an MRSA screen, 35 patients were MRSA nasal carriers. These carriers had significantly greater MELD score (mean, 16.2 compared with 13.1; P =.02) and Child scores (mean, 10 versus 9; P =.001) than noncarriers. The incidence of posttransplantation MRSA infection was significantly higher in MRSA carriers (31% versus 9%; P =.002). The incidence of other posttransplantation infection was not significantly different in the two groups. There was no significant difference in survival between the two groups (1-year patient survival, 74% and 82%, respectively). Patients carrying MRSA are predisposed to an increased risk of sepsis after liver transplantation with a trend to increased mortality. Screening for MRSA should be considered in high-risk patients being assessed for liver transplantation.

Adolescent↗

Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study.

CONTEXT: The outcome of patients receiving mechanical ventilation for particular indications has been studied, but the outcome in a large number of unselected, heterogeneous patients has not been reported. OBJECTIVE: To determine the survival of patients receiving mechanical ventilation and the relative importance of factors influencing survival. DESIGN, SETTING, AND SUBJECTS: Prospective cohort of consecutive adult patients admitted to 361 intensive care units who received mechanical ventilation for more than 12 hours between March 1, 1998, and March 31, 1998. Data were collected on each patient at initiation of mechanical ventilation and daily throughout the course of mechanical ventilation for up to 28 days. MAIN OUTCOME MEASURE: All-cause mortality during intensive care unit stay. RESULTS: Of the 15 757 patients admitted, a total of 5183 (33%) received mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean (SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall mortality rate in the intensive care unit was 30.7% (1590 patients) for the entire population, 52% (120) in patients who received ventilation because of acute respiratory distress syndrome, and 22% (115) in patients who received ventilation for an exacerbation of chronic obstructive pulmonary disease. Survival of unselected patients receiving mechanical ventilation for more than 12 hours was 69%. The main conditions independently associated with increased mortality were (1) factors present at the start of mechanical ventilation (odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR, 3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway pressure >35 cm H(2)O), and (3) developments occurring over the course of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO(2) to fraction of inspired oxygen <100). CONCLUSION: Survival among mechanically ventilated patients depends not only on the factors present at the start of mechanical ventilation, but also on the development of complications and patient management in the intensive care unit.

Adult↗