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.

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.

Chest pain with angiographically insignificant coronary arterial obstruction. Clinical presentation and long-term follow-up.

Among 3,242 coronary angiograms performed from November 1972 through October 1975 at the Massachusetts General Hospital, 175 patients had normal coronary arteries or luminal narrowings of less than 30 per cent. All patients were studied for chest pain, and none had experienced prior myocardial infarction. Subsequent information was available in 159 patients over a mean follow-up period of 42.7 months. There were no deaths, and only one myocardial infarction occurred during this period. However, among the patients followed, continued chest pain with episodes occurring at least once monthly was present in 54 per cent. In addition, 17 per cent of all patients required subsequent hospitalization and 44 per cent continued to receive antianginal medication. Nearly half of the group (46 per cent) suffered some limitation of activity, and 22 per cent stated that they had either changed jobs or stopped work because of chest pain. Continuing chest pain was significantly more common in women and in patients who had experienced chest pain for more than one year before angiography. However, typicality of chest pain for angina or the occurrence of electrocardiographic changes of ischemia prior to angiography did not predict continued chest pain during the follow-up period. Thus, although mortality and morbidity are low in this group of patients, the syndrome of chest pain with angiographically insignificant coronary artery obstruction has an important impact on the lives of a majority of those affected.

Controlled trial of oral acyclovir in the therapy of recurrent herpes simplex genitalis. A preliminary report.

A randomized, placebo-controlled, double-blind study was performed to evaluate the efficacy and toxicity of orally administered acyclovir in the treatment of patients with recurrent herpes simplex genitalis (HSG). A total of 107 patients from centers in Burlington, Vermont, and San Diego, California, were entered into the study within 48 hours of the onset of lesions. Patients who received acyclovir shed virus for 1.8 +/- 0.6 days (mean +/- SEM) compared with 2.8 +/- 1.2 days for those who received placebo. The duration of shedding from genital lesions of patients in the acyclovir-treated group was significantly less than from lesions of patients who received placebo (p = 0.016 by a logrank test). An analysis of the toxicity of the drug was performed in 52 of the study participants. Acyclovir was well-tolerated and no alterations were observed in measurements of bone marrow, liver, or kidney function. Orally administered acyclovir is a promising antiviral compound for the treatment of recurrent HSG.

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.

Oral anticoagulant therapy control: evidence that INR expression improves the inter-laboratory comparability of results--the Bologna oral anticoagulant control exercise.

The aims of the present study were: 1) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) "on field" validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposed to percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral anticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements, thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.

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.

An unusual case of congenital double coronary arteriovenous fistula.

A double coronary arteriovenous fistula (CAVF) was observed in a ten-year-old girl. A large, tortuous, and elongated right coronary artery, communicating with the right ventricle, was detected by two-dimensional echocardiography and confirmed at angiography. To our knowledge, no echocardiographic recognition of the origin and termination of a CAVF has been reported previously. Moreover, another fistula, connecting the left anterior descending coronary artery with the main pulmonary artery was also detected by selective left coronary arteriography. The anatomy of double CAVF was confirmed on surgery. A right CAVF draining into the right ventricle and a left CAVF draining into the main pulmonary artery seemed to be a very unusual combination.

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.

Clinical significance of serum pancreatic enzymes in the quiescent phase of chronic pancreatitis.

The most commonly used serum enzymes in pancreatic diseases are total amylase, pancreatic isoamylase, lipase and trypsin. To determine which of these enzymes is the most useful in the diagnosis of clinically quiescent chronic pancreatitis and which enzyme best reflects exocrine functional reserve, we studied 22 healthy control subjects, 44 patients with gastrointestinal, liver and biliary tract diseases, and 25 patients with chronic pancreatitis. On the basis of duodenal intubation, the latter were divided into two subgroups: one group of 13 patients with slight to moderate secretion deficiency and another of 12 patients with severe exocrine insufficiency. Of the enzymes studied, lipase, trypsin and pancreatic isoamylase are equally suitable for the evaluation of function in severe chronic pancreatitis, but not for the early diagnosis of the disease. Results for total amylase are not reliable so that its use in the study of chronic pancreatitis is not advisable.

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.

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.

Echocardiographic assessment of the inferior vena cava wall motion for studies of right heart dynamics and function.

Using subcostal echocardiography, 97 patients with diseases involving the right side of the heart and 15 normal subjects were examined in order to study the inferior vena cava (IVC) wall motion. All cases had a diagnostic cardiac catheterization and routine echocardiogram. The jugular pulse (JP) was recorded in 35 random cases contemporary to the IVC and tricuspid valve (TV) tracings. The aim of the study was to evaluate the variations of the IVC diameters in different cardiopathies and in relation to the right atrial mean pressure and the time-relationship of the IVC wall motion related to the cardiac rhythm and cycle, respiratory events, and JP and TV waves. The a, b, v, and y waves were identified on the IVC tracings and related to the respective waves of the JP and the points of closure and opening of the TV. The IVC a and v waves were coincident with the TV closure and opening, and therefore, considered as moments of maximal presystolic and systolic filling of the IVC. The JP a wave inscribed before, whereas the v wave did so after the same IVC waves, respectively. The IVC a wave was due to the atrial contraction and influenced by the cardiac rhythm. The emptying index (EI) was calculated from the diameters in a and b as a - b/a X %, whereas the collapsability index (CI) was calculated from the expiratory and inspiratory diameters as Ex - In/Ex X %, obtaining a good correlation with the right atrial mean pressure. Finally, the percentage systolic pulsation (SP) was calculated from the diameters in b and v as b - v/b X %. The indices of function of the IVC have been very useful in the evaluation of patients with raised heart pressure, tricuspid regurgitation, and pericardial effusion. From the present investigation it results that the IVC wall motion, more so than the JP waves, is an expression of right atrial and ventricular events, and that the above indices are an expression of the atrial and ventricular function in relation to the hemodynamic situation.

The use of receiver operating characteristic (ROC) curves analysis in the evaluation of the diagnostic efficiency of serum pseudouridine as a tumor marker.

The biochemical parameters used in this study were: (1) serum pseudouridine, expressed as nmols/mL; (2) pseudouridine index, expressed as mol to mol ratio of serum pseudouridine versus serum creatinine concentration. The receiver operating characteristic (ROC) analysis has been used to exemplify the selection of discriminant values or "cut-off points" to maximize the diagnostic utility of a biochemical tumor marker, serum pseudouridine. This marker has been used in a variety of group population samples, i.e., normal subjects, subjects affected by several nonneoplastic diseases, subjects with neoplastic disorders in less advanced or more advanced stages, and finally in a sample population of patients affected by lymphomas and leukemias of different types. An analysis of the relative ROC curves allowed the selection of cut-off values that maximize the diagnostic efficiency or, alternatively, the diagnostic sensitivity or the diagnostic specificity for pseudouridine parameters, and has allowed the comparison of the two tests to answer the same clinical question.

[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.

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.