The dark side of current analytic methods for Bence Jones Proteinuria.

OBJECTIVE: Bence Jones proteinuria (BJP) refers to monoclonal free immunoglobulin light chains detected in urine, deriving from the clonal expansion of plasma cells in the bone marrow in patients with plasma cell dyscrasias, associated with monoclonal gammopathies of uncertain origin. This review summarizes routinely diagnostic procedures to assess BJP highlighting critical steps of pre-analytical, analytical, and post-analytical phases. QUALITATIVE AND QUANTITATIVE METHODS: The best option for BJP detection is the first morning void urine sample and immunofixation electrophoresis detection technique (IFE) the recommended method, with the employment of specific polyvalent antisera. Other qualitative tests for a quick evaluation of BJP are currently available. Densitometric analysis performed on the 24-hour urine is the recommended method to quantify BJP. To overcome the 24-hour collection, it is possible to use morning urine sample and correlate the assessed value of BJP to creatininuria. In addition to the traditional ones, we here reviewed screening methods currently used to avoid false negatives and reduce the time around test (TAT), together with immunochemical quantification methods for increased sensitivity, after checking BJP by IFE. Mass spectrometry emerges as a new challenge in the determination of BJP. CONCLUSIONS: The employment of different based-assays methods may be useful for diagnostic purposes to improve the accuracy of BJP monitoring in monoclonal gammopathies.

Assessing changes in stethoscope hygiene during COVID-19: a multi-centre cross-sectional study.

BACKGROUND: The COVID-19 (SARS-CoV-2) pandemic has increased infection control vigilance across several modes of patient contact. However, it is unknown whether hygiene pertaining to stethoscopes, which carry the potential for pathogenic contamination, has also shifted accordingly. AIM: To characterize pandemic-related changes in stethoscope hygiene. METHODS: We surveyed healthcare providers at three major medical centres. Questions quantitatively (Likert scale and frequency) assessed stethoscope hygiene beliefs and practices with two components: before and during COVID-19. Participants were grouped based on performance of optimal stethoscope hygiene (after every patient) before and during COVID-19. Groups were compared using χ2 and analysis of variance (ANOVA). FINDINGS: Of the 515 (10%) who completed the survey, 55 were excluded (N = 460). Optimal hygiene increased from 27.4% to 55.0% (P < 0.001). There were significant increases in Likert scores for all questions pertaining to knowledge of stethoscope contamination (P < 0.001). Belief in stethoscope contamination increased (P < 0.001) despite no change in perceived hygiene education. Resident physicians were less likely compared with attending physicians and nurses to have adopted optimal hygiene during COVID-19 (P < 0.001). CONCLUSION: Despite a positive shift in stethoscope hygiene during COVID-19, optimal hygiene was still only performed by around half of providers. Educational interventions, particularly targeting early-career providers, are encouraged.

High progesterone levels on the day of HCG administration do not affect the embryo quality and the reproductive outcomes of frozen embryo transfers.

OBJECTIVES: The aim of this study was to evaluate the impact of pre- mature progesterone rise on the day of human chorionic gonadotropin (hCG) administration on the outcome of in vitro fertilization (IVF) of frozen embryo transfer (FET) cycles using cleavage-stage embryos. METHODS: This was a retrospective, cohort study of 131 ovarian stimulation cycles followed by cleavage-stage frozen embryo transfers. The first group consisted of women undergoing FET due to premature luteinization during controlled ovarian stimulation (n = 56, P ≥1.2 ng/ml). The controls were represented by women undergoing FET not complicated by high progesterone levels at induction (n = 75, P < 1.2 ng/ml). For both groups, the progesterone was measured on the day of hCG administration and the fertilization rate, cleavage rate, implantation rate, clinical pregnancy rate, ongoing pregnancy rate and Top-Quality Embryos (TQE) rates were compared. RESULTS: The increase of progesterone in patients of the Group A had no significant effects on the number of oocytes retrieved or available for the insemination. The fertilization rate, cleavage rate and implantation rates, as well as the clinical pregnancy rate and ongoing pregnancy were very similar in both study groups. The analysis of TQE rates between the two groups indicated a roughly comparable result. CONCLUSIONS: The results of this study showed that progesterone elevation on the day of hCG administration did not affect the outcomes of IVF with frozen embryos at cleavage stage. This study therefore confirms that for patients with high progesterone levels the right way to obtain a healthy pregnancy should be to delay the embryo transfer at a successive FET cycle, not associated with the ovarian stimulation.

[Stress imaging in coronary artery disease: state of the art]. / Stress imaging nella cardiopatia ischemica: stato dell'arte.

To date, several diagnostic tools allow an accurate non-invasive evaluation of coronary artery disease; this is due to the great progress in echocardiographic and nuclear imaging techniques in the last 10 years. The large availability of different stress imaging techniques allows to choose the most appropriate technique for each patient according to the clinical characteristics. This paper presents the state of the art of echocardiographic and nuclear stress imaging for the diagnosis of coronary artery disease and for the prognostic stratification of infarcted patients. Advantages and limits of the different techniques are described rather than putting in competition echo and nuclear cardiology as has often been done in the past. Cardiologists should select among the various techniques on the basis of clinical characteristics of single patients, center's experience and an objective evaluation of economical aspects.

Tibial speed of sound in term and preterm infants.

The tibial speed of sound (SOS) was measured in 91 healthy singleton infants between 31 and 42 weeks of gestation and 12 sick preterm infants. In healthy infants, the tibial SOS was associated with corrected gestational age (r = 0.40, p < 0.001) but not birth weight. The median tibial SOS in 12 sick preterm infants (2,772, range 2,566-2,934 m/s), whose corrected gestational age was between 31 and 42 weeks, was lower (p < 0.001) than that of 69 healthy gestation-matched healthy infants (3,100, range 2,870-3,381 m/s). Tibial SOS measurements may allow radiation-free assessment of metabolic bone disease of prematurity.

Gender differences in the risk of ischemic stroke associated with aortic atheromas.

BACKGROUND AND PURPOSE: Atherosclerotic plaque of the proximal portion of the aorta is associated with an increased risk of ischemic stroke in the elderly. Different cutoffs of plaque thickness have been used in the literature for risk stratification and have been applied to both men and women. However, the assumption that the relationship between plaque thickness and stroke risk is the same in the 2 genders has not been proven. The aim of this study was to evaluate whether the prevalence of different degrees of aortic plaque thickness differed in men and women with ischemic stroke. METHODS: We performed transesophageal echocardiography in 152 patients aged >59 years with acute ischemic stroke (76 men and 76 women) and in 152 control subjects of similar age (70 men and 82 women). Odds ratios (ORs) for ischemic stroke with 95% CIs for different plaque thickness definitions were calculated for the overall group and separately for men and women by logistic regression analysis after adjusting for age, arterial hypertension, and hypercholesterolemia. RESULTS: Aortic plaques >/=4 mm were significantly more frequent in men than in women (31.5% versus 20.3%, respectively; P:=0.025) and were associated with ischemic stroke in both men (adjusted OR 6.0, CI 2.1 to 16.8) and women (adjusted OR 3. 2, CI 1.2 to 8.8). However, plaques 3 to 3.9 mm in thickness had a significant association with stroke in women (adjusted OR 4.8, CI 1. 7 to 15.0) but not in men (adjusted OR 0.8, CI 0.2 to 3.0). Plaques <3 mm were not associated with a significantly increased stroke risk for either sex. CONCLUSIONS: Smaller aortic plaques are significantly associated with ischemic stroke in women but not in men. If the increased prevalence of smaller plaques in women is confirmed to be associated with increased risk for embolic stroke, different cutoff points may have to be adopted in men and women for risk stratification and for decisions regarding medical intervention.

Aortic atheroma morphology and the risk of ischemic stroke in a multiethnic population.

BACKGROUND: Protruding atheromas in the aortic arch are an independent risk factor for ischemic stroke in the elderly. However, the role of atheroma morphologic characteristics (ulceration and mobility) has been less well characterized. Moreover, data have been obtained in predominantly white populations, and little is known about the association between atheromas and stroke in minorities. METHODS AND RESULTS: We performed transesophageal echocardiography in 152 elderly patients with stroke (58 white, 45 black, 49 Hispanic) and in 152 age- and race/ethnicity-matched control patients. Atheromas were classified as small (<4 mm in thickness), large noncomplex (> or =4 mm, no ulceration or mobility), and complex (ulcerated or mobile). Logistic regression analysis was performed to assess the risk of stroke associated with different definitions of atheroma in the overall group and in the race-ethnic strata after adjusting for the presence of other stroke risk factors. Complex atheromas were strongly associated with stroke in the overall group (22.4% in cases, 2.6% in control patients; adjusted odds ratio [OR] 17.1, 95% confidence intervals [CI] 5.1 to 57.3), whereas large noncomplex atheromas conferred a mildly increased stroke risk (22.4% vs 16.5%; adjusted OR 2.4, 95% CI 1.1 to 5.1). Complex atheromas also were strongly associated with stroke in whites (adjusted OR 24. 3, 95% CI 3.9 to 150.6) and Hispanics (adjusted OR 13.9, 95% CI 1.4 to 136). In blacks, complex atheromas were significantly more frequent in cases (15.6% vs 0%; P =.006), but their absence in control patients precluded the calculation of the OR. Complex atheromas were twice as frequent in white patients with stroke (32. 3%) than in black or Hispanic patients (15.6% and 16.3%, respectively; P =.05). CONCLUSIONS: Aortic atheroma complexity rather than size is strongly associated with ischemic stroke in the elderly. Complex atheromas are significantly associated with stroke in all 3 race-ethnic subgroups.

Spontaneous resolution of pulmonary venous thrombosis after lung transplantation.

Thrombus formation at the pulmonary venous anastomotic site after lung transplantation may have catastrophic consequences, including allograft failure and stroke. However, treatment with systemic anticoagulation may facilitate bleeding in the early postoperative period. In the present report, we describe the clinical and transesophageal echocardiographic findings of pulmonary venous thrombosis in two patients in the immediate postoperative period after lung transplantation. Treatment with systemic anticoagulation was not feasible because of extensive postoperative thoracic bleeding in each instance. A conservative approach was taken on the basis of the small size of each thrombus and lack of accelerated flow velocity at the site of the thrombus. Each thrombus resolved spontaneously without clinical sequelae. These two cases suggest that thrombus size and flow velocity at the anastomotic site may be used to guide the clinical management of pulmonary venous thrombosis after lung transplantation.

Transesophageal echocardiography-guided transvenous biopsy of a cardiac sarcoma.

Transvenous endomyocardial biopsy is a well established procedure to diagnose rejection after heart transplantation as well as to assess for other cardiomyopathic processes. However, it is rarely used to obtain samples of unidentified cardiac masses. We report a case of a primary cardiac sarcoma in which the histologic diagnosis was provided by transesophageal echocardiography-guided transvenous biopsy. This procedure is accurate and can avoid the potential risk of a diagnostic thoracotomy.

Improved atrial function in bicaval versus standard orthotopic techniques in cardiac transplantation.

Atrial geometry is preserved in the bicaval technique of cardiac transplantation. Using Doppler echocardiography, we investigated the impact of this technique on preservation of atrial function and found that echocardiographic indexes of atrial function are improved in bicaval cardiac transplants versus the standard orthotopic transplants.

Effects of exposure to high altitude on plasma endothelin-1 levels in normal subjects.

OBJECTIVE: To assess whether the hypoxia associated with exposure to high altitude affects plasma endothelin-1 levels, and whether changes in endothelin-1 are related to those in systemic and pulmonary blood pressure. DESIGN: Eight normal subjects ascended Mount Everest to an altitude of 5050 m within a period of 8 days (study 1) and 10 ascended Mount Rosa in the Italian Alps to an altitude of 4559 m within 2 days (study 2). In study 1 systemic blood pressure, heart rate, haematocrit, haemoglobin oxygen saturation (evaluated by percutaneous oximetry) and venous plasma endothelin-1 were measured several times during the ascent, and twice more during the time spent at high altitude. In study 2 the same parameters as well as systolic pulmonary pressure by echocardiography were evaluated on the second day of resting at 4559 m. In both studies, data obtained during the expeditions were compared with those collected from the same subjects at sea level. RESULTS: In study 1 plasma endothelin-1 increased progressively up to 4240 m (from 1.8 +/- 0.1 pg/ml at sea level to 2.7 +/- 0.2 pg/ml) and decreased slightly thereafter; these increments were directly related to the decrements in percutaneous oxygen saturation, which, at that altitude, fell from 98.6 +/- 0.2% at sea level to 80.8 +/- 0.4%. Blood pressure and haematocrit also rose in response to exposure to high altitude but these changes were not related to changes in endothelin-1. In study 2 the increments in plasma endothelin-1 were similar to those observed in study 1 and the changes again correlated with changes in oxygen saturation as well as with those in systolic pulmonary pressure. On average, systolic pulmonary pressure increased from 19 +/- 1 to 26 +/- 1.9 mmHg, whereas systemic blood pressure and haematocrit were unchanged. CONCLUSION: Exposure to high altitude is associated with consistent increases in plasma endothelin-1. This is probably the result of augmented secretion of the peptide in response to hypoxia and may contribute to the physiological adaptation of the pulmonary circulation to this condition.

Endothelin-releasing stimuli and calcium antagonists in normal and pathological conditions.

BACKGROUND: Endothelin-1 is a potent vasoconstrictive peptide which circulates in blood at very low concentrations. It is mostly released from endothelial cells towards the vascular smooth muscle cells. Therefore studies addressed at increasing endothelin-1 production using physical stimuli may easily fail to cause sizeable modifications in plasma endothelin levels. Upright posture and exposure to cold, the two maneuvers so far most commonly used in humans, often have inconsistent effects on plasma endothelin-1. RECENT FINDINGS: In recent studies we have found that exposure to high altitude (4500-5000 m) caused, in normal subjects, significant increases in endothelin-1 which were correlated with those of mean arterial pressure and of systolic pulmonary pressure. CONCLUSIONS: Hypobaric hypoxia appears to stimulate the secretion of endothelin-1 and this response may contribute to the adaptation by the systemic and pulmonary circulation to the stress of altitude. If this can be confirmed, calcium antagonists, which are known to antagonize endothelin-1 mediated vasoconstriction, may be used to alleviate the pulmonary hypertension that occasionally occurs under these specific circumstances.

Serum pseudouridine in the diagnosis of acute leukaemias and as a novel prognostic indicator in acute lymphoblastic leukaemia.

The serum level of pseudouridine, a modified nucleoside deriving mainly from t-RNA catabolism, was evaluated in 66 acute leukaemia patients at diagnosis to investigate its diagnostic and prognostic value, and its potential as a parameter with which to classify subtypes of the disease. Serum pseudouridine, measured by high performance liquid chromatography, was increased in acute lymphoblastic leukaemia patients (90% according to the pseudouridine index, which is the serum pseudouridine/creatinine ratio), and in acute myeloblastic leukaemia patients (75% according to the pseudouridine index). The increase was higher in the L3 than in the L1 and L2 subtypes. In the acute lymphoblastic leukaemia group there was a highly significant inverse correlation between serum pseudouridine levels and the most common end-point parameters used to assess disease outcome in leukaemia (i.e., complete remission rate, disease-free survival, and overall survival). In addition, 83% of patients with serum pseudouridine values < 5.5 nmol/mL were alive and in complete remission 12 months after the initial diagnosis, while only 11% of patients with serum pseudouridine values > 5.5 nmol/mL were alive and none were disease-free after the same period. This study: 1. demonstrates that the diagnostic sensitivity of the pseudouridine index is high in adult acute lymphoblastic leukaemia and good in acute myeloblastic leukaemia; 2. suggests that the serum pseudouridine assay can contribute to the classification of adult acute lymphoblastic leukaemia; and 3. demonstrates unequivocally that both pseudouridine assay and the pseudouridine index are excellent independent prognostic markers for acute lymphoblastic leukaemia.

UCSD's MedPics: implementation and impact on the curriculum.

MedPics is a computer-based image delivery system with supporting text fields and on-screen graphics to assist in key feature identification. It has been used by the University of California, San Diego as an integral part of the Human Disease course since 1992. Initially created to support pathology and histology, the program has now expanded to include hematology. MedPics has had a positive impact on the second year curriculum for which it was created. Moreover, use of this program has improved student attitudes toward computer-based resources and increased faculty interest in instructional development.

Post-surgical deep vein thrombosis prevention: evaluation of the risk/benefit ratio of fractionated and unfractionated heparin.

An open controlled study was carried out to assess the efficacy and tolerance of a new low molecular weight heparin for the prevention of post-surgical deep vein thrombosis and pulmonary embolism. Forty-five patients undergoing abdominal surgery mainly for neoplasm, gallstones and gastric ulcers were administered 7,500 AXaU of low molecular weight heparin subcutaneously, 2 hours before surgery and once a day for 7 days after. Heparin calcium (15,000 IU subcutaneously per day) was used as a comparison drug in 45 control subjects, matched for age, sex and type of operation. Deep vein thrombosis was identified with clinical parameters, radio-labelled fibrinogen uptake test, echo-doppler and venography; pulmonary embolism with clinical examination, chest X-rays and/or scintigraphy. No episodes of deep vein thrombosis occurred in the low molecular weight heparin-treated patients, whilst there was 1 episode, without pulmonary embolism, in the control group. The consumption of blood and haemoderivatives for transfusions was higher in the heparin calcium group. Only in this group, furthermore, did 5 patients have to suspend antithrombotic treatment due to severe haemorrhages. General tolerance of the two drugs was identical and very good.