Impact of pH on Urine Chemistry Assayed on Roche Analyzers.

BACKGROUND: The pH may impact the concentration of certain urinary parameters, making urine pre-treatment questionable. METHODS: 1) Determining the impact of pH in vitro on the urinary concentration of chemistry parameters assayed on Roche Modular analyzers. 2) Evaluating whether concentrations depended on pH in non-pretreated urines from patients. RESULTS: 1) The optimal urinary pH values for each measurement were: 6.3 ± 0.8 (amylase), < 5.5 (calcium and magnesium), < 6.5 (phosphorus), > 6.5 (uric acid). Urinary creatinine, sodium and urea concentrations were not pH-dependent. 2) In urines from patients, the pH was negatively associated with the concentration of some urinary parameters. However, concentrations of all the parameters were strongly and positively correlated with urinary creatinine, and relationships with pH were no longer evidenced after creatinine-normalization. CONCLUSIONS: The need for urine pH adjustment does not seem necessary when considering renal function. However, from an analytical and accreditation standpoint, the relationship between urine pH and several parameters justifies its measurement.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.

Pulmonary Embolism Rule-out Criteria vs D-dimer testing in low-risk patients for pulmonary embolism: a retrospective study.

STUDY OBJECTIVES: The Pulmonary Embolism Rule-out Criteria (PERC) score has shown excellent negative predictive value; however, its use in the European population with high prevalence of PE is controversial. In Europe, PERC is not part of routine practice. For low-risk patients, guidelines recommend D-dimer testing, followed if positive by imaging study. We aimed to study the rate of diagnosis of PE after D-dimer testing in PERC-negative patients that could have been discharged if PERC was applied. METHOD: This was a multicenter retrospective study in Paris, France. We included all patients with a suspicion of PE who had D-dimer testing in the emergency department, low pre-test probability, and a negative PERC score (that was retrospectively calculated). Patients with insufficient record to calculate PERC score were excluded. The primary end point was the rate of PE diagnosis before discharge in this population. Secondary end points included rate of invasive imaging studies and subsequent adverse events. RESULTS: We screened 4301 patients who had D-dimer testing, 1070 of whom were PERC negative and could be analyzed. The mean age was 35 years and 46% were men. D-dimer was positive (>500 ng/L) in 167 (16%) of them; CTPA or V/Q scan was performed in 153 (14%) cases. PE was confirmed in 5 cases (total rate 0.5%, 95% confidence interval 0.1%-1.1%). Fifteen patients (1%) experienced non-severe adverse events. CONCLUSION: D-dimer testing in PERC-negative patients led to a diagnosis of PE in 0.5% of them, with 15% of patients undergoing unnecessary irradiative imaging studies.

Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial.

BACKGROUND: Decrease of circulating tumor cells (CTC) during treatment is an independent prognostic factor in metastatic breast cancer (MBC). We specifically evaluated the impact of CTC on brain metastasis outcome. METHODS: HER2-positive MBC with brain metastasis not previously treated with whole-brain radiotherapy received first-line combination of lapatinib and capecitabine in a phase II study. CTC were detected at baseline and day 21 (CellSearch). RESULTS: Median follow-up of the 44 analyzed patients was 21.2 months. The central nervous system objective response (CNS-OR) rate was 66%. At baseline, 20 of 41 assessable patients for CTC (49%) had ≥1 CTC (range 1-301, median 3) and 9 (22%) had ≥5 CTC. At day 21, 7 of 38 patients (18%) had ≥1 CTC (P = 0.006, versus baseline), and CTC had disappeared in 11 patients. CNS-OR rate was significantly higher in patients with no CTC at day 21 [25 of 31 (80%) versus 2 of 7 (29%), P = 0.01]. The 1-year overall survival rate was 83.9% in patients with no CTC at day 21 versus 42.9% in patients with ≥1 CTC (P = 0.02). CONCLUSIONS: This is the first report showing a correlation between CNS metastasis response, outcome and early CTC clearance under targeted treatment of HER2+ MBC. CLINICAL TRIALS NUMBER: NCT00967031.

[Alteration of general state in a woman with polyethylene breast implants since 1967. About an exceptional clinical case]. / Altération de l'état général chez une patiente porteuse d'implants mammaires en polyéthylène depuis 1967. À propos d'un cas clinique exceptionnel.

We report the case of a patient with mammary implants for 42 years. She presented for three years a change of the general state with clinicobiological demonstrations of indefinite origin, and a progressive bilateral increase of her mammary volume until it became exceptional. The surgery of explantation allowed the retreat of two masses of almost 6kg. The analysis did not put in evidence any malignant process but confirmed that it was about prostheses in polyethylene. In one year of recession, a considerable improvement of her general state was observed.

[Paget's disease of the nipple and differential diagnosis]. / Maladie de Paget du mamelon et principaux diagnostics différentiels.

Clinical evaluation of the nipple-areolar complex is a routine component of the breast screening examination. All persistent unilateral nipple lesion should be viewed with suspicion and Paget's disease of the nipple should be considered. The diagnosis is established by nipple scrape cytology. It is a rare variant of ductal carcinoma in situ. The breast imaging work-up should include a search for an underlying malignancy, present in over 80% of cases, not infrequently multifocal. Preoperative MRI is useful if breast conservative surgery is contemplated because of the high rate of occult malignancy on mammograms and ultrasound. Erosive adenomatosis of the nipple is a benign process that may simulate Paget's disease isolated to the nipple. Less frequently, pagetoid basal cell carcinoma, Bowen's disease and melanoma may be more difficult to differentiate clinically and share the unilateral and chronic features of Paget's disease. Biopsy is needed for diagnosis. Cutaneous extension of a breast cancer is rare but should be suspected in patients with retraction and/or fixed nipple. Eczema is characterized by the bilateral nature of the process, the absence of nipple deformity, the presence of flare-ups and the favorable response to local steroid therapy.

[Diagnosis of flat epithelial atypia (FEA) after stereotactic vacuum-assisted biopsy (VAB) of the breast: What is the best management: systematic surgery for all or follow-up?]. / Lésions de métaplasie cylindriques atypiques (MCA) diagnostiquées par macrobiopsies assistées par aspiration: opportunité d'une exérèse chirurgicale?

OBJECTIVE: FEA lesions group two histological types: columnar cell hyperplasia with atypia (CCHA) and columnar cell change with atypia (CCA). The increasing use of VAB has resulted in increased detection of isolated FEA lesions. The aim of this study was to define the best management possible for these patients: which cases may not need excision? MATERIAL AND METHODS: From our database of 780 VABs carried out from 2000 to 2004, 59 patients with FEA were diagnosed. Cases in which no surgery was performed or all features were not available were excluded, thus excluding 19 cases. Forty patients with FEA were included. We reviewed clinical and mammographic characteristics, histological biopsy, and the corresponding surgically excised tissue features. RESULTS: VAB yielded 25 cases of CCHA and 15 cases of CCA. Surgery revealed seven ductal carcinoma cases (four invasive, three in situ); nine benign lesions, and 24 with atypia (19 FEA and six atypical ductal hyperplasia). We found two features related to the risk of cancer: the presence and the size of hyperplasia. All carcinomas were found within the CCHA lesions. No cancer was yielded when size was less than 10 mm within CCA lesions and lesions that were totally removed. CONCLUSION: We recommend surgical excision when CCHA greater than 10 mm is found on the VAB or it is incompletely removed. CCA lesions or CCHA less than 10 mm or totally removed may obviate systematic surgery.

[Architectural distortion and diagnostic difficulties]. / Distorsions architecturales et difficultés diagnostiques.

Identification of architectural distortion requires a good practice of mammography. Prevalence is estimated at 6% of detected abnormalities in screening programs. Under this denomination are gathered focal architectural distortion with predictive positive value (PPV) of 10% and stellate images without central densification, which are more suspicious (PPV 50%). In order to establish a diagnosis, false images must be eliminated by other views. Minimal architectural distortion have to be investigated by other techniques (sonography, MRI percutaneous biopsy) in order to define the best strategy for further management. Stellate images suggestive of radial scars must be surgically removed. The relationships between radial scars and tubular carcinoma are discussed. A particular attention is required for post traumatic or post surgical scars if it exist a high risk of local recurrence or controlateral carcinoma specially after conservative or oncoplastic surgery.

Plasma ionized calcium in brain-dead patients.

BACKGROUND: The mechanism of brain death-induced myocardial dysfunction remains debatable. Hypocalcemia is known to induce reversible myocardial dysfunction. However, the incidence of hypocalcemia and its effect on myocardial function during brain death is unknown. METHODS: In 54 consecutive brain-dead patients, we measured plasma total and ionized calcium concentrations, QT and corrected QT intervals, and left ventricular ejection fraction area (LVEFa), using transesophageal echocardiography. RESULTS: 49 (91%) of brain-dead patients had a decrease in total plasma total calcium concentration but only 19 (35%) had a decrease in plasma ionized calcium. Corrected total plasma calcium failed to predict ionized calcium concentration and QT intervals were not significantly different in normo and hypocalcemic patients. The LVEFa was not significantly different between normo and hypocalcemic patients (53 +/- 13 versus 50 +/- 20%), and no correlation was found between LVEFa and ionized calcium (R = 0.02, NS). Hypocalcemic patients required greater doses of dopamine (8.2 +/- 5.2 versus 5.0 +/- 3.4 micrograms.kg-.min-1, p < 0.02) to maintain arterial pressure. Hypocalcemia was associated with a higher volume loading and a lower plasma protide concentration which reflected hemodilution. CONCLUSION: A decrease in plasma ionized calcium is not frequent, rarely severe, and probably not the main mechanism of myocardial dysfunction in brain-dead patients. Hypocalcemic patients required higher doses of dopamine, suggesting a decrease in systemic resistance. Only direct measurement of ionized calcium can assess plasma calcium ion status in brain-dead patients.

Factors influencing cardiopulmonary effects of inhaled nitric oxide in acute respiratory failure.

The aim of this prospective study was to determine factors influencing effects of inhaled nitric oxide (NO) on the pulmonary circulation and on gas exchange in critically ill patients with acute lung injury. Twenty-one hypoxemic patients with acute respiratory failure (PaO2 = 127 +/- 69 mm Hg during intermittent positive pressure ventilation, FiO2 = 1), were mechanically ventilated with 2 ppm NO and pure oxygen. The effect of positive end-expiratory pressure (PEEP) on alveolar recruitment was assessed on an anatomic basis using a high-resolution and spiral thoracic computed tomographic (CT) scan. Four conditions were studied in random order: zero end-expiratory pressure (ZEEP), ZEEP + 2 ppm NO, 10 cm H2O PEEP, 10 cm H2O PEEP + 2 ppm NO. During ZEEP and PEEP, NO significantly decreased pulmonary vascular resistance index (PVRI), mean pulmonary arterial pressure (MPAP), true pulmonary shunt (Qs/QT), and alveolar dead space (VDA/VT) and significantly increased PaO2 (p < 0.01). During ZEEP, NO-induced decreases in PVRI (delta PVRI) and MPAP (delta MPAP) were significantly correlated to baseline PVRI and MPAP (delta PVRI = -0.5 PVRI + 125, r = 0.97, p < 0.01 and delta MPAP = -0.28 MPAP + 4.8, r = 0.69, p < 0.05). These changes were not potentiated by PEEP-induced alveolar recruitment. The NO-induced increase in PaO2 (delta PaO2) was not significantly correlated with baseline PaO2 but was correlated with baseline PVRI (delta PaO2 = 0.11 PVRI + 30, r = 0.67, p < 0.05). In patients in whom PEEP was associated with alveolar recruitment, NO increased PaO2 by 66 +/- 24 mm Hg during ZEEP and by 104 +/- 26 mm Hg during PEEP (p < 0.01). In patients in whom PEEP did not induce alveolar recruitment, the NO-induced increase in PaO2 was similar during ZEEP and PEEP conditions (+70 +/- 15 mm Hg versus +76 +/- 12 mm Hg, NS). In patients with adult respiratory distress syndrome, factors determining NO-induced improvement in arterial oxygenation and pulmonary vascular effects are PEEP-induced alveolar recruitment and the baseline level of pulmonary vascular resistance.

Increased signals seen in globus pallidus in T1-weighted magnetic resonance imaging in cirrhotics are not suggestive of chronic hepatic encephalopathy.

Increased, symmetrical signals of varying intensity in the globus pallidi on T1-weighted (T1W) images, without corresponding signals on T2-weighted (T2W) images, have been reported previously in chronic hepatic failure. It has been suggested that these signals are characteristic of chronic hepatic encephalopathy. To test this hypothesis, we evaluated the relationship of magnetic resonance imaging (MRI) abnormalities with ammonia, albumin, bilirubin, prothrombin time, ascites, clinical encephalopathy, and neuropsychological tests in 46 patients (16 with alcohol-induced cirrhosis and 30 with non-alcohol-induced cirrhosis). T1W signal and cortical atrophy were graded by a neuroradiologist in a blinded fashion. Eleven patients had no T1W signal, 18 had minimal T1W signal, and 17 had high T1W signal. Twenty-five patients had no cortical atrophy, 14 had mild atrophy, and 7 had moderate atrophy. Cortical atrophy was noted more commonly in patients with alcohol-induced liver disease. The neuropsychological tests correlated significantly with albumin, prothrombin time, Child-Pugh's score, clinical encephalopathy, and ammonia. T1W signal and cortical atrophy did not correlate with the neuropsychological tests, clinical encephalopathy, ascites, albumin, prothrombin time, ammonia, or Child-Pugh's score. Patients with high T1W signal showed significant correlation with bilirubin (P < .005). This study suggests that globus pallidus signal in T1W images observed in liver disease are not indicators of chronic hepatic encephalopathy as previously assumed.

[The pitfalls of the clearance concept in hemodialysis]. / Les pièges du concept de clairance en hémodialyse.

The "clearance concept" is rigorously defined by the physicists and bioengineers. However its extension in clinical routine of dialysis therapy is not easy, but essential also to understand the rationale on which is based the currently widely used Kt/V index. The purpose of this paper is to describe the difficulties and pitfalls encountered in measuring the clearance of a substance either provided by a dialyzer or observed in a dialyzed patient. Ambiguities in the definition of clearance may account for sometimes moot estimations of the Kt/V index.

Variation in arterial to end-tidal CO2 tension differences during anesthesia in the "kidney rest" lateral decubitus position.

The course of arterial to end-tidal carbon dioxide tension difference [P(a-ET)CO2] was evaluated during general anesthesia in 25 patients scheduled for renal surgery performed in the "kidney position." The difference between arterial PCO2 (PaCO2) corrected to body temperature, and end-tidal PCO2 (PETCO2) measured by mass spectrometry was assessed after induction of anesthesia, after placement in the lateral decubitus position with back arched over a kidney bridge ("kidney position"), and every 20 min until the patients were replaced in the supine position at the end of the surgical procedure. Heart rate, arterial blood pressure, and esophageal temperature were simultaneously recorded. After induction of anesthesia, when the patients were lying supine (T1), P(a-ET)CO2 was 4.8 +/- 3.9 mm Hg (mean +/- SD). Placing the patients in the kidney position (T2) induced a significant increase in P(a-ET)CO2 (to 7.9 +/- 3.5 mm Hg; P less than 0.01). These alterations occurred without any significant change in mean arterial blood pressure or heart rate. A progressive increase in mean P(a-ET)CO2 occurred with maintenance of anesthesia; P(a-ET)CO2 reached 8.8 +/- 4.1 mm Hg (P less than 0.05 vs T2) and 8.9 +/- 4.4 mm Hg (P less than 0.05 vs T2) at 65 and 85 min, respectively, after lateral decubitus positioning. Large variations between and within patients were observed. Although stable mean arterial pressure was maintained, these changes were associated with a significant decrease in body temperature. These results demonstrate that P(a-ET)CO2 increases when patients are placed in the kidney position and may vary with the prolongation of anesthesia in this situation.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in ventilation, oxygen uptake, and carbon dioxide output during recovery from isoflurane anesthesia.

Recovery from inhalation anesthesia is often marked by the occurrence of postoperative tremor that resembles shivering, which is known to be associated with an increase in oxygen uptake (VO2), CO2 output (VCO2), and minute ventilation (VE). This study determined the time course of the ventilatory changes observed during the first hour of recovery from isoflurane anesthesia. Ten patients (ASA PS 1) scheduled for minor orthopedic surgery (knee arthroscopy) were included in this study. Anesthesia was induced with thiopental (5 mg/kg) and maintained with 70% N2O and isoflurane (1-2%) in oxygen, allowing spontaneous ventilation. In the recovery room, after N2O had been discontinued, patients were connected to a Beckman Metabolic measurement cart, which allowed a continuous monitoring of VE, VO2, VCO2, and PETCO2. Postoperative tremor was observed in all patients within 7.1 +/- 1.2 min (mean +/- SEM) after isoflurane discontinuation and was associated with a marked increase in the following: VO2, from 173 +/- 26 ml/min at the end of anesthesia to 457 +/- 88 ml/min; VCO2, from 149 +/- 18 ml/min at the end of anesthesia to 573 +/- 98 ml/min; and VE, from 6.8 +/- 0.7 l/min at the end of anesthesia to 16.6 +/- 2.8 l/min (values obtained 20 min after isoflurane discontinuation). In three patients during intense shivering, VO2, VCO2, and VE reached peak values higher than 800 ml/min, 1,300 ml/min and 30 l/min, respectively. This study shows that postoperative tremor following isoflurane anesthesia may be associated with prolonged and large increases in oxygen uptake, CO2 output, and minute ventilation.

Respiratory effects of the Jarvik-7 artificial heart.

In five anesthetized patients with a Jarvik-7 artificial heart, pulmonary volume displacements generated by cardiogenic oscillations were measured using an indirect spirometric method. Consequences on gas exchange were also evaluated during a 15-min period of apnea by use of a tracheal insufflation of pure O2 at a constant flow rate of 20 l/min. The Jarvik-7 artificial heart generated a mean pulmonary volume displacement of 105 +/- 29 (SD) ml/heart beat. After 15 min of apnea, arterial PCO2 (PaCO2) significantly increased from 29 +/- 5 to 47 +/- 6 (SD) Torr. PaCO2 increased by 0.8 Torr/min from the 5th to the 15th min of apnea. Mean arterial PO2, mean pulmonary shunt, mean O2 consumption, and mean metabolic production of CO2 did not change significantly during the apnea period. Because cardiac output was kept constant during the study, O2 transport was adequately maintained throughout the apnea period. In patient 1, where the period of apnea was continued for 60 min, PaCO2 progressively increased until the 45th min and then remained stable at 61 Torr during the last 15 min of apnea. This "plateau" corresponded to an alveolar ventilation of 3,907 ml/min, representing 69% of the alveolar ventilation calculated during conventional mechanical ventilation. In conclusion, the Jarvik-7 artificial heart provides a potent respiratory support through the cardiogenic oscillations it generates.

[Factors influencing mixed venous oxygen saturation in intensive care]. / Facteurs influençant la SvO2 en réanimation.

Changes in mixed venous blood oxygen saturation (SvO2) were studied in 2 groups of patients. Group I patients (n = 10) were all hypoxaemic, suffering from acute respiratory failure, requiring that FIO2 be maintained at 1 throughout the study; respiratory and haemodynamic conditions were improved using PEEP and cardiovascular support. On the other hand, Group II patients (n = 13) were non-hypoxaemic patients with circulatory shock in whom FIO2 was gradually increased, and the haemodynamic status was improved using positive inotropic drugs (dopamine, dobutamine, adrenaline, amrinone). All 23 patients had a Swan-Ganz catheter set up for monitoring; all the usual haemodynamic and respiratory parameters were measured. Haematocrit values were kept at the same level throughout the study. Haemodynamic parameters were measured each time a new therapeutic procedure was carried out. No close relationship between SvO2 changes and changes in cardiac index or O2 consumption were found. However, a close relationship existed between changes in SvO2 and changes in O2 extraction (EAO2): SvO2 = -EAO2 + 102 (Group I; r = 0.90, n = 54); SvO2 = -1.2 EAO2 + 103 (Group II; r = 0.93, n = 66). A strong relationship was also found between changes in SvO2 and in FIO2 in each patient of Group II. In the complicated physiological set-up of an intensive care patient, SvO2 reflects oxygen extraction. A fall in SvO2 is related to an altered oxygen demand: oxygen supply ratio. In the most seriously ill patients, there is no relationship between changes in SvO2 and cardiac index.