Objective: Increasing evidence links TGF-beta 1 to progression of renal fibrosis including its association with diabetic nephropathy (DN). Current ELISA assays are not sensitive enough to measure TGF-beta 1 in the urine of many clinically healthy individuals, even those with established renal disease. The objective of this study was to validate a sensitive urinary assay for TGF-beta 1 and compare levels between healthy controls and patients with established DN.Design and methods: An ELISA method (R&D Systems) was utilized together with an amplification step to assay TGF-beta 1 in urine samples from 190 patients with DN and 80 healthy controls.Results: Using an ELAST (Perkin Elmer, Inc) amplification step, the ELISA for urinary TGF-beta 1 had a limit of quantification of 15.6 pg/mL and limit of detection of 7 pg/mL. Preliminary studies demonstrated that TGF-beta 1 was stable if urine was frozen promptly at -70 degrees C without preservatives. Using this assay, 22/80 controls (27%) had detectable levels of urinary TGF-beta 1 (range <7 to 40.9 pg/mL; mean +/- SD 6.4 +/- 11.1 pg/mL). This was significantly lower (p < 0.0001) than in the DN group in whom 114/190 (60%) had detectable levels of urinary TGF-beta 1 (range <7 to 526.4 pg/mL; mean +/- SD 20.4 +/- 45.8 pg/mL). Urinary protein and TGF-beta 1 concentrations demonstrated modest correlation in patients with DN (r = 0.47, P < 0.001). TGF-beta 1 measurement in patients with DN did not demonstrate significant association with progression of proteinuria or increase in serum creatinine during the next 12 months of follow-up.Conclusion: We have validated a sensitive ELISA assay for urinary TGF-beta 1, and demonstrated correlations with the degree of proteinuria and higher levels in patients with DN compared to controls. Additional study will be necessary in order to determine if serial testing can predict renal prognosis independent of known prognostic factors for patients with DN. (c) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Objective: To review treatment and outcomes of septic shock in patients with pulmonary hypertension (PH) managed at a tertiary care institution.Design, setting and patients: We identified consecutive patients with non-cardiac PH (non-Group 2 in the World Health Organization classification) who were treated for septic shock in four intensive care units at a tertiary care institution between July 2004 and July 2007. Patients with a left ventricular ejection fraction <50%, diastolic dysfunction, pericardial effusion or significant valve disease were excluded. Descriptive statistics were used to analyse the data.Main outcome measures: Hospital mortality, duration of vasopressor and ventilatory support, length of hospital and ICU stay.Results: The final group for analysis comprised 82 patients; The major causes of PH were chronic obstructive pulmonary disease, interstitial lung disease and portopulmonary hypertension. PH was mild in 46 patients (56%), moderate in 21(26%) and severe in 15 (18%). Vasopressor treatment was initiated in 69 patients (84%) within the first 48 hours: noradrenaline was most commonly used (53 patients, 65%), and 51 patients (62%) were treated with more than one agent. Sixty-seven patients (82%) were mechanically ventilated, and 33 (40%) required renal replacement therapy. Forty-three patients (52%) survived to hospital discharge; 23 (28%) remained alive at 1 year. Hospital mortality increased with severity of PH: 28% in mild, 67% in moderate and 80% in severe PH. Non-survivors were more likely to have plateau pressures beyond 30 cm H2O while mechanically ventilated within the first 48 hours in the ICU (56% v 29%, P=0.03), to develop atrial fibrillation (AF) (46% v 12%, P < 0.001), and to require longer vasopressor support (mean, 5.3 v 2.6 days, P=0.003). In a multivariate logistic regression analysis, severity of PH (odds ratio [OR], 1.55; 95% CI, 1.04-2.46; P=0.04), new-onset AF (OR, 6.51; 95% CI, 2.24-22.07; P < 0.001) and longer duration of vasopressor support (OR, 1.15; 95% CI, 1.03-1.34; P=0.04) were associated with increased hospital mortality.Conclusions: The severity of PH, new-onset AF, and longer vasopressor support were associated with poor outcomes in patients with PH who developed severe sepsis and septic shock.

An 82 year-old male patient with past medical history of coronary artery disease, hypertension, COPD, diabetes mellitus (Type 2), chronic kidney disease, Alzheimer’s disease and recently treated diarrhea was brought to the emergency department (ED) from home after he vomited, aspirated and developed severe respiratory distress. He was emergently intubated on arrival to ED. Shortly after intubation, he became hypotensive, bradycardic and went into cardiac arrest. During ACLS, the patient required a total of 17 minutes of CPR and 2 shocks. He received 2 liters of normal saline solution intravenously and multiple doses of epinephrine, sodium bicarbonate and calcium gluconate. He was also started on amiodarone and epinephrine infusions. Blood tests were obtained before the cardiac arrest, with a limited panel collected immediately after the patient regained circulation. These values are shown in Table 1.

BACKGROUND:Chronic kidney disease in liver transplant (OLT) recipients is often attributed to calcineurin inhibitors (CNI) toxicity, but little is known about the spectrum of their renal histological lesions.METHODS:Between 1988 and 2008, 1698 OLTs were performed in our center. We retrospectively analyzed clinical and histological data on 23 recipients (1.4%) referred for kidney biopsy (KB).RESULTS:Median age at OLT was 50.2 yr, 65.2% were men, 30.4% had hepatitis C, and 95.7% were given CNI. KB was performed 6.9 yr (median) post-OLT. Median creatinine was 1 mg/dL pre-OLT and 2.2 mg/dL at KB. Main pathological diagnoses were focal segmental and global glomerulosclerosis (n = 8, 34.8%), glomerular diseases (7, 30.4%), CNI toxicity (2, 8.7%), and diabetic nephropathy (2, 8.7%). Moderate/severe interstitial fibrosis, tubular atrophy, arteriosclerosis, and hyalinosis were present in 47.8%, 43.5%, 60.9%, and 56.5%, respectively. Twelve patients (52.5%) reached end-stage renal disease (ESRD) and 17 (73.9%) died. Death was more common among those reaching ESRD, but the difference was not significant (83.3% vs. 63.6%, p = 0.37).CONCLUSION:Renal histology is variable and not limited to CNI toxicity in OLT recipients referred for KB. Whether management based on KB findings can directly improve outcomes remains unclear.

Vascular access dysfunction causes morbidity in hemodialysis patients. This study examined the generation and pathobiological significance of superoxide anion in a rat femoral arteriovenous fistula (AVF). One week after AVF creation, there was increased production of superoxide anion accompanied by decreased total superoxide dismutase (SOD) and Cu/Zn SOD activities and induction of the redox-sensitive gene heme oxygenase-1. Immunohistochemical studies of nitrotyrosine formation demonstrated that peroxynitrite, a product of superoxide anion and nitric oxide, was present in increased amounts in endothelial and smooth muscle cells in the AVF. Because uncoupled NOS isoforms generate superoxide anion, and NOS coupling requires tetrahydrobiopterin (BH 4 ) as a cofactor, we assessed NOS uncoupling by determining the ratio of BH 4 to dihydrobiopterin (BH 2 ); the BH 4 -to-BH 2 ratio was markedly attenuated in the AVF. Because Src is a vasculopathic signaling species upstream and downstream of superoxide anion, such expression was evaluated; expression of Src and phosphorylated Src was both markedly increased in the AVF. Expression of NADPH oxidase (NOX) 1, NOX2, NOX4, cyclooxygenase (COX) 1, COX2, p47 phox , and p67 phox was all unchanged, as assessed by Western analyses, thereby suggesting that these proteins may not be involved in increased production of superoxide anion. Finally, administration of tempol, a superoxide anion scavenger, decreased neointima formation in the juxta-anastomotic venous segment and improved AVF blood flow. We conclude that the AVF exhibits increased superoxide anion generation that may reflect the combined effects of decreased scavenging by SOD and increased generation by uncoupled NOS, and that enhanced superoxide anion production promotes juxta-anastomotic stenosis and impairs AVF function.

Background: To improve the safety of ventilator care and decrease the risk of ventilator-induced lung injury, we designed and tested an electronic algorithm that incorporates patient characteristics and ventilator settings, allowing near-real-time notification of bedside providers about potentially injurious ventilator settings. Methods: Electronic medical records of consecutive patients who received invasive ventilation were screened in three Mayo Clinic Rochester intensive care units. The computer system alerted bedside providers via the text paging notification about potentially injurious ventilator settings. Alert criteria included a Pao2/Fio2 ratio of <300 mm Hg, free text search for the words "edema" or "bilateral + infiltrates" on the chest radiograph report, a tidal volume of >8 mL/kg predicted body weight (based on patient gender and height), a plateau pressure of >30 cm H2O, and a peak airway pressure of >35 cm H2O. Respiratory therapists answered a brief online satisfaction survey. Ventilator-induced lung injury risk was compared before and after the introduction of ventilator-induced lung injury alert. Findings: The prevalence of acute lung injury was 42% (n = 490) among 1,159 patients receiving >24 hrs of invasive ventilation. The system sent 111 alerts for 80 patients, with a positive predictive value of 59%. The exposure to potentially injurious ventilation decreased after the intervention from 40.6 ± 74.6 hrs to 26.9 ± 77.3 hrs (p = .004). Interpretations: Electronic medical record surveillance of mechanically ventilated patients accurately detects potentially injurious ventilator settings and is able to influence bedside practice at moderate costs. Its implementation is associated with decreased patient exposure to potentially injurious mechanical ventilation settings.

Objective Acute Physiology and Chronic Health Evaluation (APACHE) is most widely used as a mortality prediction score in US intensive care units (ICUs), but its calculation is onerous. The authors aimed to develop and validate automatic mapping of physicians' admission diagnoses to structured concepts for automated APACHE IV calculation. Methods This retrospective study was conducted in medical ICUs of a tertiary healthcare and academic centre. Boolean-logic text searches were used to map admission diagnoses, and these were compared with conventional APACHE database entry by bedside nurses and a gold-standard physician chart review. The primary outcome was APACHE IV predicted hospital mortality. The tool was developed in a larger cohort of ICU patients. Results In a derivation cohort of 192 consecutive critically ill patients, the diagnosis coefficient coded by three different methods had a positive correlation, highest between manual and gold standard (r(2)=0.95; mean square error (MSE)=0.040) and least between manual and automatic tool (r(2)=0.88; MSE=0.066). The automatic tool had an area under the curve (95% CI) value of 0.82 (0.74 to 0.90) which was similar to the physician gold standard, 0.83 (0.75 to 0.91) and standard manual entry, 0.81 (0.73 to 0.89). The Hosmer-Lemeshow goodness-of-fit test demonstrated good calibration of automatically calculated APACHE IV score (χ(2)=6.46; p=0.6). The automatic tool demonstrated excellent discrimination with an area under the curve value of 0.87 (95% CI 0.83 to 0.92) and good calibration (p=0.58) in the validation cohort of 593 patients. Conclusion A Boolean-logic text search is an efficient alternative to manual database entry for mapping of ICU admission diagnosis to structured APACHE IV concepts.

We report a case of relapsing mesangial and endocapillary proliferative glomerulonephritis (GN) associated with a periodic fever syndrome. The patient presented 11 times in >4 years with acute febrile episode followed in 1-3 days by hematuria, thrombocytopenia and other symptoms of acute GN with variable severity of acute kidney injury. In three episodes, the patient required renal replacement therapy for 7, 10 and 2 treatments, respectively. Shortly after the acute symptoms of the febrile episode had resolved each time, the kidney function would recover and the serum creatinine would return to baseline. Two kidney biopsies obtained during separate episodes showed acute tubular injury along with morphological changes resembling post-infectious GN but with no clinical evidence to support an infectious etiology. Multiple treatment regimens were unable to control the disease. Symptoms were alleviated by rituximab but did not completely remit. Stable remission of the periodic fever and GN was finally achieved after anakinra therapy was initiated 18 months ago. Since then, the patient had several episodes of documented infection without high fever and nephritic kidney manifestations. His kidney function remained stable with normal serum creatinine.

PURPOSE: Most of clinical research studies require data collection from medical records. Manual extraction of the data can produce errors, is time consuming, expensive and require some level of expertise from data collectors. Development and implementation of Electronic Medical Records (EMR) has opened new opportunities for automatic data extraction. In order to validate accuracy of the automatic data extraction we compared it to the same data obtained by manual chart review.

Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classifi cation of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response.

Coronary artery disease is the most common cause of morbidity and mortality in industrialized countries. In recent decades, the number of coronary artery bypass graft surgery procedures has slowly declined owing to continued conversion to minimally invasive percutaneous transluminal coronary angioplasty (PTCA) and stent therapy (1). However, negative vessel remodeling, vessel elastic recoil, and neointima proliferation as a result of a healing response to vessel injury leads to narrowing of the vessel lumen, thus leading to a high incidence (30–80%) of restenosis (2). Introduction of the stent showed a significant decrease in vessel remodeling and elastic recoil at the site of intervention and clearly demonstrated the superiority of stent implantation to PTCA alone with respect to restenosis in de novo coronary lesions (3,4). However, it was also evident that neointimal proliferation is not affected by stenting technique (5).