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Background: We sought to investigate the mutual interplay between bone, glucose and lipid metabolism in a wide cohort of community-based subjects., Methods: We studied 1240 blood donors (F/M ratio 1/3.2, mean age 41.9 ± 11.7 SD). Serum ionized (Ca ++ ), magnesium (Mg ++ ), 25-hydroxy-vitamin D [25(OH)D], PTH-1-84, 1,25-dihydroxyvitamin D [1,25(OH) 2 D], total cholesterol (C), HDL-C, triglycerides and glucose were measured and LDL-C levels were calculated in all subjects., Results: 25(OH)D negatively correlated with BMI (R = -0.11), PTH (R = -0.16) ( p < 0.0001), total C (R = -0.06, p < 0.05) and triglycerides (R = -0.13, p < 0.0001) and positively with 1,25(OH) 2 D (R = 0.12) and creatinine (R = 0.17) ( p < 0.0001). Serum PTH positively correlated with total C (R = 0.08, p < 0.01), LDL-C (R = 0.1, p < 0.001), triglycerides (R = 0.09, p < 0.01) and glucose (R = 0.15, p < 0.0001) and negatively with HDL-C (R = -0.09, p < 0.01). The odds of showing abnormal serum triglycerides and HDL-C increased as 25(OH)D decreased ( p < 0.0001 and p < 0.03) and PTH increased ( p < 0.03 and p = 0.05), while the odds of showing abnormal LDL-C levels increased in association with elevated PTH ( p < 0.01)., Conclusion: Vitamin D, PTH, glucose and lipid metabolism are mutually influenced. Hypovitaminosis D predisposes toward worsening lipid profiles through the actions of PTH, while serum PTH levels per se associate with higher glucose and LDL-C levels.

Night shift work has been associated with cardiovascular and metabolic disease, endocrine and immunological disorders. Published studies have reported that a reduced total sleep time with sleep-wake cycle alterations were associated with a reduced rate of humoral response following vaccination. Our study aimed to evaluate the association between night shift work and serological status for HBV among workers employed in a university hospital in Rome. We evaluated medical records of 986 HCWs working at Tor Vergata Policlinic of Rome. We screened all study subjects for anti-HBs IgG, anti-HBc IgG and HBsAg. Serological protection for HBV was evaluated in relation to sex, age group, job task, risk setting and night shift work status. Protective titer was found in 856 (86.8%) study participants and the mean titer was significantly high in females, in subjects aged less than 40 years, in night shift workers and in high-risk setting workers. After adjustment for study covariates, night shift work was no longer associated with an HBV-protective titer. This finding suggests that a vaccination strategy for dampening HBV transmission should be carefully addressed in health care workers (HCWs) doing night shift.

Background: The aim of this study was to evaluate the efficacy and feasibility of a peri-operative bloodless medicine and surgery (BMS) protocol in reducing severe post-operative anaemia (haemoglobin [Hb] <7 g/dL) in Jehovah's Witnesses undergoing cytoreductive surgery for advanced epithelial ovarian cancer., Materials and Methods: This was a single-institution retrospective study enrolling Jehovah's Witnesses who underwent elective bloodless surgery for advanced epithelial ovarian cancer between October 2017 and April 2020. All patients followed a standardised bloodless medicine and surgery protocol based on ferric carboxymaltose and erythropoietin if indicated., Results: Twenty-five patients with a mean age of 61.7 years (range, 35-80) were enrolled. Pre-operatively, ten patients (40%) were mildly anaemic (mean Hb of 10.2 g/dL [range, 9.2-11.4]) and received ferric carboxymaltose. Only four (16%) patients had severe anaemia after surgery (mean Hb of 6.1 g/dL [range, 4.1-6.9]) and received ferric carboxymaltose and erythropoietin. Compared to patients with a post-operative Hb ≥7 g/dL, those with Hb <7 g/dL had higher mean body mass index (25.8±1.8 vs 30.7±1.8 kg/m 2 ; p<0.001), mean baseline CA125 (236.1±184.5 vs 783.7±273.5 IU/mL; p<0.001), median surgical complexity score (2 vs 10; p<0.001), and rate of post-operative complications (14.3 vs 100%; p<0.001). Moreover, these patients had a longer mean operating time (3.4±0.6 vs 5.5±0.4 h; p<0.001), duration of stay in hospital (5.5±0.7 vs 24.0±9.8 days; p<0.001), and time to adjuvant chemotherapy (27.2±2.6 vs 65.3±13.4 days; p<0.001)., Discussion: The use of a multidisciplinary bloodless medicine and surgery protocol is safe and effective in reducing the rate of severe post-operative anaemia and improving surgical and oncological outcomes of Jehovah's Witnesses with advanced epithelial ovarian cancer. Further large-scale, prospective studies are required to confirm these data.

Background and Aims: It is known that the highest COVID-19 mortality rates are among patients who develop severe COVID-19 pneumonia. However, despite the high sensitivity of chest CT scans for diagnosing COVID-19 in a screening population, the appearance of a chest CT is thought to have low diagnostic specificity. The aim of this retrospective case-control study is based on evaluation of clinical and radiological characteristics in patients with COVID-19 (n = 41) and no-COVID-19 interstitial pneumonia (n = 48) with mild-to-moderate symptoms., Methods and Results: To this purpose we compared radiological, clinical, biochemical, inflammatory, and metabolic characteristics, as well as clinical outcomes, between the two groups. Notably, we found similar radiological severity of pneumonia, which we quantified using a disease score based on a high-resolution computed tomography scan (COVID-19 = 18.6 ± 14.5 vs n-COVID-19 = 23.2 ± 15.2, p = 0.289), and comparable biochemical and inflammatory characteristics. However, among patients without diabetes, we observed that COVID-19 patients had significantly higher levels of HbA1c than n-COVID-19 patients (COVID-19 = 41.5 ± 2.6 vs n-COVID-19 = 38.4 ± 5.1, p = 0.012). After adjusting for age, sex, and BMI, we found that HbA1c levels were significantly associated with the risk of COVID-19 pneumonia (odds ratio = 1.234 [95%CI = 1.051-1.449], p = 0.010)., Conclusions: In this retrospective case-control study, we found similar radiological and clinical characteristics in patients with COVID-19 and n-COVID-19 pneumonia with mild-to-moderate symptoms. However, among patients without diabetes HbA1c levels were higher in COVID-19 patients than in no-COVID-19 individuals. Future studies should assess whether reducing transient hyperglycemia in individuals without overt diabetes may lower the risk of SARS-CoV-2 infection., Competing Interests: Declaration of competing interest All authors declare that they have no personal or financial conflicts of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Context: Type 2 diabetes (T2D) shows a high mortality rate, partly mediated by atherosclerotic plaque instability. Discovering novel biomarkers may help identify high-risk patients who would benefit from more aggressive and specific managements. We recently described a serum resistin and multicytokine inflammatory pathway (REMAP), including resistin, interleukin (IL)-1β, IL-6, IL-8, and TNF-α, that is associated with cardiovascular disease., Objective: We investigated whether REMAP is associated with and improves the prediction of mortality in T2D., Methods: A REMAP score was investigated in 3 cohorts comprising 1528 patients with T2D (409 incident deaths) and in 59 patients who underwent carotid endarterectomy (CEA; 24 deaths). Plaques were classified as unstable/stable according to the modified American Heart Association atherosclerosis classification., Results: REMAP was associated with all-cause mortality in each cohort and in all 1528 individuals (fully adjusted hazard ratio [HR] for 1 SD increase = 1.34, P < .001). In CEA patients, REMAP was associated with mortality (HR = 1.64, P = .04) and a modest change was observed when plaque stability was taken into account (HR = 1.58; P = .07). REMAP improved discrimination and reclassification measures of both Estimation of Mortality Risk in Type 2 Diabetic Patients and Risk Equations for Complications of Type 2 Diabetes, well-established prediction models of mortality in T2D (P < .05-< .001)., Conclusion: REMAP is independently associated with and improves predict all-cause mortality in T2D; it can therefore be used to identify high-risk individuals to be targeted with more aggressive management. Whether REMAP can also identify patients who are more responsive to IL-6 and IL-1β monoclonal antibodies that reduce cardiovascular burden and total mortality is an intriguing possibility to be tested., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess the magnitude of COVID-19 spread and the associated risk factors among health care workers (HCWs), we conducted an in-hospital survey in a central Italian COVID Hospital., Methods: Participants underwent nasopharyngeal swab and/or serum collection for SARS-CoV-2 IgG examination. We divided participants according to working status, into rotating-night shift workers (r-NSW) and day-workers., Results: We found 30 cases of COVID-19 infection in a total of 1180 HCWs (2.5%). Most COVID-19-positive hospital employees were r-NSWs with significantly higher BMI than that of individuals who tested negative. After adjustment for covariates, night work and BMI > 30 were associated with a markedly greater risk of COVID-19 diagnosis (OR 3.049 [95%CI 1.260-7.380] and OR 7.15 [95%CI 2.91-17.51], respectively)., Conclusions: Our results describe a low prevalence of COVID-19 infection among HCWs at a central Italian COVID Hospital. COVID-19 infection risk appears to be associated with obesity and night shift work, thus supporting the need for careful health surveillance among frontline HCWs exposed to COVID-19.

Background: The aim of this study was to evaluate the efficacy and feasibility of a peri-operative bloodless medicine and surgery (BMS) protocol in reducing severe post-operative anaemia (haemoglobin [Hb] <7 g/dL) in Jehovah's Witnesses undergoing cytoreductive surgery for advanced epithelial ovarian cancer., Materials and Methods: This was a single-institution retrospective study enrolling Jehovah's Witnesses who underwent elective bloodless surgery for advanced epithelial ovarian cancer between October 2017 and April 2020. All patients followed a standardised bloodless medicine and surgery protocol based on ferric carboxymaltose and erythropoietin if indicated., Results: Twenty-five patients with a mean age of 61.7 years (range, 35-80) were enrolled. Pre-operatively, ten patients (40%) were mildly anaemic (mean Hb of 10.2 g/dL [range, 9.2-11.4]) and received ferric carboxymaltose. Only four (16%) patients had severe anaemia after surgery (mean Hb of 6.1 g/dL [range, 4.1-6.9]) and received ferric carboxymaltose and erythropoietin. Compared to patients with a post-operative Hb ≥7 g/dL, those with Hb <7 g/dL had higher mean body mass index (25.8±1.8 vs 30.7±1.8 kg/m 2 ; p<0.001), mean baseline CA125 (236.1±184.5 vs 783.7±273.5 IU/mL; p<0.001), median surgical complexity score (2 vs 10; p<0.001), and rate of post-operative complications (14.3 vs 100%; p<0.001). Moreover, these patients had a longer mean operating time (3.4±0.6 vs 5.5±0.4 h; p<0.001), duration of stay in hospital (5.5±0.7 vs 24.0±9.8 days; p<0.001), and time to adjuvant chemotherapy (27.2±2.6 vs 65.3±13.4 days; p<0.001)., Discussion: The use of a multidisciplinary bloodless medicine and surgery protocol is safe and effective in reducing the rate of severe post-operative anaemia and improving surgical and oncological outcomes of Jehovah's Witnesses with advanced epithelial ovarian cancer. Further large-scale, prospective studies are required to confirm these data.

Background: While the inverse relationship between serum ionized calcium (Ca 2+ ) and PTH is well-established, the relationship between 25(OH)D and PTH showed conflicting results. The study aimed to evaluate the relative contributions of age, sex, serum Ca 2+ , ionized magnesium (Mg 2+ ), 25(OH)D and 1,25(OH) 2 D in regulating PTH secretion in healthy subjects., Methods: This is a secondary analysis of an observational study performed from March 2014 to July 2015 carried out in 2259 blood donors (1652 men and 607 women, age range 18-68 years). Subjects with parathyroid disorders and taking drugs that affect mineral metabolism were excluded., Results: Significant correlations [between Ca 2+ and PTH (r = -0.223, p < 0.001), 25(OH)D and PTH (r = -0.178, p < 0.001) and between PTH and age (r = 0.322, p < 0.001)] were found. As a preliminary step to multivariate analysis, a regression tree analysis was performed using PTH as response variable and age, Ca 2+ , Mg 2+ , 25(OH)D, 1,25(OH) 2 D and sex as explanatory variables to determine the effect of each covariate on the response variable. For subjects <38 years, 25(OH)D was the most important parameter in regulating PTH. For subjects ≥38 both 25(OH)D and Ca 2+ levels regulated PTH secretion. Subjects with 25(OH)D < 13 ng/mL had average higher PTH; in this group only, subjects with Ca 2+  ≥ 1.30 mmol/L had average lower PTH compared to subjects with Ca 2+  < 1.30. The multivariate analysis showed that all variables had a significant effect (p < 0.001) on PTH. Anova Type III errors c indicated that 25(OH)D accounted for 32.1% of the total variance in PTH, Ca 2+ accounted for 18% of the total variance, BMI for 14.3%, and 1,25(OH) 2 D for 11.1%. The remaining percentage was attributable to age and sex. This was confirmed by the regression tree approach, where 25(OH)D and Ca 2+ accounted for the largest variation in the average levels of PTH., Discussion: Under stable conditions 25(OH)D plays a significant role in regulating PTH secretion. Under conditions of relative vitamin D sufficiency, Ca 2+ also plays an important role., (Copyright © 2019. Published by Elsevier Inc.)

Aims: Reinforcement of the staple line is one of the most debated technical aspects concerning laparoscopic sleeve gastrectomy (LSG). Different buttressing methods have been proposed and demonstrated to be effective in reducing the incidence of staple line bleeding, although data concerning their effort on staple line leakage are not consistent. The aim of this study was to ascertain the technical feasibility and to report the preliminary outcomes of laparoscopic use of platelet-rich plasma (PRP) to reinforce the staple line during sleeve gastrectomy., Patients and Methods: From March 2012 to May 2012, 20 patients were prospectively enrolled (10 females; mean age, 44.6 ± 11 years; mean body mass index, 42.3 ± 5.45 kg/m(2)). Type 2 diabetes mellitus was present in 4 patients, obstructive sleep apnea syndrome in 3, and hypertension in 6. LSG was performed using a 48-French bougie and gold cartridges; reinforcement of the staple lines with buttressed materials or oversewing the suture was performed excluding the last cranial cartridge. PRP was prepared by separating the platelets from autologous blood withdrawn on the same day of surgery, in order to obtain a membrane with cylindrical shape (2×5 cm) formed by fibrin and active platelets. The membrane is introduced through the 10-mm trocar and placed at the upper portion of the staple line. The overall cost for the preparation of PRP is about €15., Results: No intraoperative complications and conversions have been recorded during the surgical procedures. No deaths occurred. The mean operative time was 85 ± 31 minutes, which was not significantly increased compared with the operative time of the surgeon's overall personal series (750 cases). At 12 months of follow-up the abdominal ultrasound was negative for collections, and upper contrast showed no images indicating gastric leaks. In no case did PRP induce symptoms of rejection, infection, or adverse events., Conclusions: The use of PRP during LSG is feasible, does not increase significantly the operative time, does not require any special devices, and is cost effective. A larger cohort of patients is needed to ascertain the potential effectiveness of PRP in the prevention of postoperative staple line complications.

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by a wide range of clinical manifestations. Chronic leg ulcers are a disabling complication with repercussions on the quality of life. We report the case of a 14-year-old girl with a diagnosis of SCD who developed a chronic leg ulcer that was successfully treated with a multi-disciplinary approach, including local and systemic therapies. The role of different treatments, in particular low molecular weight heparin, in the refractory chronic leg ulcer healing process will be discussed.

Study Design Prospective cohort study. Objectives To analyze the effectiveness and practicality of using cancellous bone substitute with platelet-rich plasma (PRP) in posterolateral arthrodesis. Methods Twenty consecutive patients underwent posterolateral arthrodesis with implantation of cancellous bone substitute soaked with PRP obtained directly in the operating theater on the right hemifield and cancellous bone substitute soaked with saline solution on the right. Results Computed tomography scans at 6 and 12 months after surgery were performed in all patients. Bone density was investigated by comparative analysis of region of interest. The data were analyzed with repeated-measures variance analyses with value of density after 6 months and value of density after 12 months, using age, levels of arthrodesis, and platelet count as covariates. The data demonstrated increased bone density using PRP and heterologous cancellous block resulting in an enhanced fusion rate during the first 6 months after surgery. Conclusions PRP used with cancellous bone substitute increases the rate of fusion and bone density joining osteoinductive and osteoconductive effect.

Bronchiolar-pleural fistulas are a frequent complication of thoracic surgery. Current treatment strategies and their invasiveness are quiet different, but often surgeons decide for a new surgical intervention and definitive closure of the breach. We report the case of a bronchiolar-pleural fistula in a 75 years old man with important co-morbidities that we treated with instillation of platelet-leukocyte rich gel (PLR-G). We discuss actual indications for PLR-G as well as its possible role in thoracic surgery.

Background: Arthroscopic rotator cuff repair generally provides satisfactory results including decreased shoulder pain and improved shoulder motion. Unfortunately, imaging studies demonstrate that the retear rate associated with the available arthroscopic techniques may be high. The purpose of this study was to evaluate the clinical and magnetic resonance imaging (MRI) results of arthroscopic rotator cuff repair with and without the use of platelet-leukocyte membrane in patients with a large posterosuperior rotator cuff tear., Methods: Eighty consecutive patients with a large full-thickness posterosuperior rotator cuff tear were enrolled. All tears were repaired using an arthroscopic single-row technique. Patients were randomized to treatment either with or without a platelet-leukocyte membrane inserted between the rotator cuff tendon and its footprint. In patients treated with this membrane, one membrane was utilized for each suture anchor. The primary outcomes were the difference between the preoperative and postoperative Constant scores and the repair integrity assessed by MRI according to the Sugaya classification. The secondary outcome was the difference between the preoperative and postoperative Simple Shoulder Test (SST) scores., Results: The only significant differences between the two groups involved the patient age and the preoperative and postoperative Constant scores; the differences in the Constant score were due to differences in the shoulder pain subscore. At a mean of thirteen months of follow-up, rotator cuff retears were observed only in the group of patients in whom the membrane had not been used, and a thin but intact tendon was observed more frequently in this group as well. The use of the membrane was associated with significantly better repair integrity (p = 0.04)., Conclusions: The use of the platelet-leukocyte membrane in the treatment of rotator cuff tears improved repair integrity compared with repair without membrane. However, the improvement in repair integrity was not associated with greater improvement in the functional outcome. In fact, the Constant scores of the two groups would have been similar if the shoulder pain component (which had differed preoperatively) had been excluded.

Over the last few years, some hemocomponents have been used advantageously in clinical neurosurgical practice, not systemically via transfusion but topically as a sealant (fibrin glue). This has diverted the attention of many authors to the role of platelets in the healing process. The combination of hyper-concentrated platelets and fibrin glue (fibrinogen, XIII factor, fibronectin) with activated thrombin produces a platelet gel that can be easily applied to "difficult" wounds. This topical use of hemocomponents has gained an important role in regenerative medicine. The authors have considered the possibility of using a preparation with a high autologous platelet concentration applied in addition to autologous bone during vertebral postero-lateral fusion. The aim of the procedure is to induce a higher rate of vertebral fusion. Between November 2007 and November 2008, 14 patients (9 men and 5 women, mean age 58.9) underwent laminectomy, vertebral stabilization and postero-lateral fusion. The number of vertebral levels involved in stabilization was: 1 in 2 patients, 2 in 5 patients, 3 in 5 patients, 4 in 1 patient and 5 in 1 patient. Platelet gel was obtained by taking 16 ml of peripheral venous blood from the patient. For this procedure two patented test tubes were used for each patient, with a capacity of 8 m each. These make up the REGEN-THT(®) (Thrombocyte Harvesting Tube) system that makes it possible to obtain 8 ml of autologous platelet gel in 40-45 min. The addition of Ca gluconate and ethanol at 95% makes it possible to obtain a preparation of plasma rich in platelets and activated thrombin with a platelet concentration five times superior to the haematic one. The platelet gel is combined with fragments of autologous bone and synthetic bone during surgical operation. To allow a comparative assessment of the degree of fusion achieved with and without application of the platelet preparation in each patient, it was arbitrarily decided to use it in only one half of the operative field. All patients underwent serial CT scans 3 and 6 months after surgery as well as plain X-rays to evaluate bone fusion. The reconstructed CT images, especially in sagittal and axial planes, permitted an evaluation of the degree of vertebral fusion and "bone growth". The fusion rate was calculated measuring the increment of bone density on CT images, by means of an evaluation of the ROI (HU) in the newly formed bone, and comparing bone density within the bone callus formed by autologous and synthetic bone alone in the one to which the platelet preparation had been added. A good rate of fusion was observed in all patients. Furthermore, a comparative analysis of ROI at 3 and 6 months after surgery demonstrated a high increase in the fusion rate during the first 3 months after surgery. After 6 months the differences in ROI between the two sides had balanced out. However, at 6-month follow-up examination, bone density in the half of the surgical field in which platelet gel had been added to autologous-heterologous bone was higher in comparison to the contralateral one. Bony neoformation after posterior-lateral arthrodesis is well-evident 3 months after surgery and usually continues gradually for the following 18-24 months. The autologous platelet preparation used seems to accelerate bony deposition and to promote tissue healing, increasing bone density at the level of posterior-lateral arthrodesis. Moreover, this preparation has low production costs and is easy to apply.

Complications of the residual pleural space after pulmonary resection have been reported to be between 5% and 40% depending on the type of resection, and they increase morbidity, mortality, hospital stays, and costs. The therapeutic use of autologous prepared platelet leukocyte-enriched gel is a relatively new technology for the stimulation and acceleration of soft tissue and bone healing. This gel can be applied to a diversity of tissue. We describe the case of a successful application through a chest tube of platelet leukocyte gel to treat an infected residual pleural space that developed after pulmonary lobectomy for lung cancer.

Background and Objective: One of the chief causes of death in patients with beta-thalassemia major (TM) remains heart failure due to iron overload. We investigated possible differences in myocardial function between a population of young asymptomatic patients with TM and healthy controls all of whom underwent an echocardiographic study, including tissue Doppler (TDI) and strain imaging (SI) analysis and cardiac magnetic resonance imaging (MRI)., Methods: 30 young asymptomatic patients with TM (16 taking deferoxamine and 14 taking deferiprone) and 30 healthy subjects underwent a cardiac MRI with T2* technique and an echocardiographic evaluation including systolic myocardial velocities (Sm), early (Em) and late (Am) diastolic velocities and systolic strain (S) at the level of basal segments of the lateral left ventricle (LV), interventricular septum (Septal) and lateral right ventricle (RV) wall. The differences in T2* values and echocardiographic parameters were also compared in patients with TM subgrouped according to iron chelation therapy., Results: The following TDI and SI measures were lower in patients than in controls: LV-Sm (P < 0.05), S-LV (P < 0.001), Septal-Sm (P < 0.05), Septal-Em (P < 0.001), S-Septal (P < 0.001), RV-Sm (P < 0.001), RV-Em (P < 0.001), RV-Em/Am (P < 0.05) and S-RV (P < 0.05). Myocardial function was better in the patients receiving deferiprone than those receiving deferoxamine. T2* values were higher in controls than in patients with TM and in those treated with deferiprone than those treated with deferoxamine. MRI data well correlated with SI parameters., Conclusions: Study underlines that, even in a population of young, asymptomatic and well-chelated patients with TM, there is an impairment of myocardial function and that this condition could be easily detected by more advanced ultrasound techniques such as TDI and SI. The better indices of myocardial function in patients treated with deferiprone clearly needs confirmation from larger prospective studies.

Background: Despite recent progress in iron chelation therapy, sudden cardiac death due to malignant ventricular arrhythmias remains a vexing, clinical problem in patients with beta-thalassemia major (TM). In this study we assessed whether the major indices of QT variability, emerging tools for risk stratification of sudden cardiac death, differ in young asymptomatic patients with TM and healthy persons., Methods: Thirty patients with TM and 30 healthy control subjects underwent a 5-min electrocardiography recording to calculate the following variables: QT variance (QT(v)), QT(v) normalized for mean QT (QTVN) and QT variability index (QTVI). All subjects also underwent a two-dimensional and Doppler echocardiography study and magnetic resonance imaging (MRI) to determine cardiac and hepatic T2* values., Results: No differences were observed in clinical and conventional echo-Doppler findings in healthy control subjects and patients with TM whereas QT(v), QTVN and QTVI values were significantly higher in patients than those in controls (QT(v), P < 0.001; QTVN, P < 0.05 and QTVI, P < 0.001) and cardiac T2* and hepatic MRI T2* values were significantly lower in patients with TM (P < 0.001). The indices of temporal QT variability correlated significantly with MRI data., Conclusions: Young asymptomatic patients with TM have increased cardiac repolarization variability as assessed by QT variability indices, probably due to cardiac iron deposition. These easily assessed, non-invasive markers could be used to identify increased myocardial repolarization lability early in asymptomatic patients with TM.

Myocardial ischemia/reperfusion induces ventricular tachycardia (VT), ventricular fibrillation (VF) and a high degree of lethality. Since ACTH-(1-24) (adrenocorticotropin) protects against such injuries in rats, we investigated which melanocortin MC receptor is involved. Ischemia was produced in anesthetized rats by ligature of the left anterior descending coronary artery (5 min), and reperfusion-induced VT, VF, lethality and time-course of arterial blood pressure within the 5 min following reperfusion were evaluated. I.v. administration of the selective MC(3) receptor agonist gamma(1)-melanocyte-stimulating hormone (gamma(1)-MSH), as well as of an equimolar dose (162 nmol/kg) of both the non-selective agonist ACTH-(1-24) and alpha-MSH, significantly prevented VT and VF, and increased survival. Coronary reperfusion was followed by an abrupt and massive fall in mean arterial pressure and pulse pressure, in saline-treated rats. Treatment either with ACTH-(1-24) or gamma(1)-MSH completely prevented such fall. The protective effect of ACTH-(1-24) against the occurrence of VT, VF and lethality was neither affected by adrenalectomy, nor by i.v. pretreatment with the selective MC(4) receptor antagonist HS014 and the MC(4)-MC(5) antagonist HS059. On the other hand, the MC(3)-MC(4) receptor antagonist SHU 9119 prevented such protective effect. Moreover, the selective MC(1) receptor agonist MS05 (162 nmol/kg i.v.) failed to reduce the incidence of arrhythmias and lethality. These data demonstrate that MC(3) receptors mediate the protective effect of melanocortins in myocardial ischemia/reperfusion-induced arrhythmias, in rats.

Activation of peripheral cannabinoid CB(1) receptors contributes to hemorrhagic hypotension, and endocannabinoids produced by macrophages and platelets may be mediators of this effect. A number of studies have provided evidence that functional links exist in the mechanisms of action of cannabinoids and opioid peptides; and opioids too play an important role in the pathophysiology of hemorrhagic hypotension and shock. On the other hand, melanocortin peptides, which are the main endogenous functional antagonists of opioid peptides, have an antishock effect in animals and humans. Thus, we investigated whether an interaction exists between endocannabinoids and the endogenous opioid/antiopioid system also in a condition of hemorrhagic shock and, particularly, whether the blockade of cannabinoid CB(1) receptors potentiates the antishock effect of melanocortins. Urethane-anesthetized rats were stepwise bled until mean arterial pressure decreased to, and stabilized at, 21-23 mm Hg. In this model of hemorrhagic shock, which caused the death of all control rats within 30 min after vehicle (tween 80, 5% in saline) injection, the intravenous (i.v.) bolus injection of the cannabinoid CB(1) receptor antagonist N-piperidino-5-[4-chlorophenyl]-1-[2,4 dichlorophenyl]-4-methyl-3-pyrazolecarboxamide (SR141716A) increased mean arterial pressure, pulse pressure, respiratory rate and survival rate in a dose-related manner (0.1-3 mg/kg), an almost complete recovery of mean arterial pressure, pulse pressure and respiratory rate, and 100% survival at the end of the observation period (2 h), occurring with the dose of 3 mg/kg. The melanocortin ACTH-(1-24) (adrenocorticotropin) also produced in a dose-related manner (0.02-0.16 mg/kg i.v.) a restoration of cardiovascular and respiratory functions, and increased survival rate, an almost complete recovery and 100% survival at the end of the observation period (2 h) occurring with the dose of 0.16 mg/kg. When a subactive dose of SR141716A (0.2 mg/kg; 30% survival) was associated with a subactive dose of ACTH-(1-24) (0.02 mg/kg; 12% survival), a complete reversal of the shock condition was obtained with 100% survival at the end of the 2-h observation period. The present results show that the concurrent inhibition of both endogenous opioid and cannabinoid systems produces a reversal of hemorrhagic shock more effective than that produced by the inhibition of either of them. These data suggest that functional interactions between endocannabinoids and opioid/antiopioid are at work also in the pathophysiology of hemorrhagic shock.

Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organ systems. Plasma therapy has significantly reduced the mortality rate. Infections, pregnancy, cancers, drugs, and surgery were frequently associated with the initial episodes and relapses. Women who are either pregnant or in the postpartum period make up 10-25% of TTP patients, suggesting the interrelationship between TTP and pregnancy. The introduction of aggressive treatment with plasma transfusion or plasmapheresis improved maternal and fetal survival rates. We describe a case of a first successful pregnancy concomitant to a late relapse of TTP, in which the identification of important risk factors for both TTP and pregnancy allowed us easier hematological and obstetrical management. Proposed guidelines for pregnancy-related TTP management and a brief review of current treatment options for this rare condition are also included.

Melanocortin peptides exert, in rats, a protective effect in myocardial ischaemia followed by reperfusion, or permanent occlusion of a coronary artery. Moreover, melanocortins have an anti-shock effect. Since the mechanism of the life-saving effect of these peptides in haemorrhagic shock includes an essential brain loop, we aimed to determine whether the central nervous system (CNS) is also involved in the protective effect against the outcome of short-term myocardial ischaemia followed by reperfusion. Ischaemia was produced in anaesthetized rats by ligature of the left anterior descending coronary artery for 5 min. Reperfusion-induced ventricular tachycardia (VT), ventricular fibrillation (VF) and lethality, and the time-course of arterial blood pressure over 5 min following reperfusion were evaluated. Groups of 8-14 rats were used. Intravenous (i.v.) injection of ACTH-(1-24) (0.16-0.48 mg/kg) during the ischaemic period dose dependently reduced the incidence of VT, VF and of lethality. In saline-treated rats, coronary reperfusion caused VT in 100% animals, VF in 86%, and death in 86%. The highest dose of ACTH-(1-24) (0.48 mg/kg) completely prevented the occurrence of VT, VF and death in all rats (P<0.005). Moreover, the melanocortin peptide prevented the fall in mean arterial pressure (MAP) occurring during reperfusion. Treatment with ACTH-(1-24) by the intracerebroventricular (i.c.v.) route also reduced the incidence of VT, VF and lethality, and prevented the fall in MAP in a dose dependent manner. Complete (100%) protection occurred with an i.c.v. dose (0.048 mg/kg) 10 times less than that needed by the i.v. route. The present data show that in the protective effect of melanocortin peptides against the injury after myocardial ischaemia/reperfusion, the i.c.v. route of administration is more effective than the i.v. route. They suggest that a CNS mechanism, not yet identified, may be involved.

Background and Objectives: Neurologic symptoms are present in 60% of patients with thrombotic thrombocytopenic purpura (TTP) on initial examination and ultimately develop in about 90% of cases during the course of the disease. Despite central nervous system involvement being frequent, abnormalities in the brain of patients with TTP are infrequent on neuroimaging (CT/MRI) and neurophysiologic (EEG) evaluation, often reversible and mainly limited to symptomatic stages of the disease. The aim of our study was to establish the value of a complete neurologic screening as part of the work up of TTP., Design and Methods: We prospectively evaluated 16 TTP patients, performing serial neurologic, neuroimaging and EEG examinations, independently of the presence of an objective central nervous system involvement., Results: Our study shows that a complete neurologic evaluation is of modest help in improving the diagnosis of TTP, but may be useful for the neurologic management., Interpretation and Conclusions: Accurate neuroimaging and, especially, EEG evaluation and monitoring allowed us to identify patients who could benefit from anticonvulsive therapy, avoiding the unnecessary administration of the latter. The prognostic utility of complete neurologic screening in TTP remains to be conclusively demonstrated in larger prospective neurologic studies.

The influence of the melanocortin peptide ACTH-(1-24) (adrenocorticotropin) on the consequences of short-term coronary ischemia (5 min) followed by reperfusion, and the effect of the long-acting melanocortin [Nle(4),D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-MSH) on the damage induced by a permanent coronary occlusion, were investigated in anesthetized rats. Ischemia was produced by ligature of the left anterior descending coronary artery. Reperfusion-induced arrhythmias [ventricular tachycardia (VT), ventricular fibrillation (VF)] and survival rate within the 5 min following reperfusion, blood levels of free radicals detected 2 min after reperfusion by electron spin resonance spectrometry, and amount of healthy myocardial tissue, measured 72 h after permanent coronary occlusion on immunohistologically stained serial sections, were evaluated. Postischemic reperfusion induced VT in all saline-treated rats, and VF and death in a high percentage of animals (87%). In rats treated i.v. (2.5 min after coronary occlusion) with ACTH-(1-24) (0.16-0.48 mg/kg) there was a significantly dose-dependent reduction in the incidence of arrhythmias and lethality. Ischemia/reperfusion caused a large increase in free radical blood levels; treatment with ACTH-(1-24) (0.48 mg/kg i.v.) almost completely prevented this increase. In rats subjected to permanent coronary occlusion, the amount of healthy myocardial tissue was much reduced in saline-treated rats, while in rats treated s.c. with NDP-MSH (0.27 mg/kg every 12 h) it was significantly higher. The present data demonstrate, for the first time, an unforeseen property of melanocortin peptides, i.e., their ability to significantly reduce both heart ischemia/reperfusion injury and size of the ischemic area induced by permanent coronary occlusion.

Background: G-CSF-mobilized PBPCs are considered the richest source of HPCs for both autologous and allogeneic transplantation, but, despite their wide use, the best dose and schedule for G-CSF administration have not been definitively established., Study Design and Methods: With a target of collecting from the peripheral blood > or = 4 x 10(6) CD34+ cells per kg of body weight of the recipient, the short-course administration of glycosylated G-CSF (gly-G-CSF) in 30 healthy donors for an allogeneic transplantation was investigated. Gly-G-CSF was given subcutaneously at a dose of 10 microg per kg per day in two divided doses over 3 days and was followed by a leukapheresis (on the 4th day) 12 hours after the last dose., Results: A median of 53.5 circulating CD34+ cells per microL (range, 19-190) was found in the 30 donors on the day of first leukapheresis, which allowed a median CD34+ cell collection of 6.0 x 10(6) per kg of body weight of the donor and 6.5 x 10(6) per kg of body weight of the recipient. In 25 (83%) of 30 donors, a single procedure was sufficient to collect the target CD34+ cells, while in the other 5, two leukapheresis procedures were required. Hematologic reconstitution was observed in all patients at a median of 14 days (range, 10-23) for neutrophils and 14.5 days (range, 11-46) for platelets. With a median infusion of 3.9 x 10(8) CD3+ T-lymphocytes per kg of body weight of the recipient (range, 1.3-7.8), acute and chronic GVHD occurred in 13 (43%) of 30 and 15 (60%) of 25 evaluable patients, respectively. After a median follow-up of 337 days from transplant, 22 (73%) of 30 patients are alive in complete remission., Conclusion: A schedule consisting of 3-day administration of gly-G-CSF followed by a single leukapheresis can be proposed and widely accepted by healthy donors, as 84 percent of them reach the target in the estimated time with a reduced drug exposure. The cost of the procedure is reduced, in terms of both the growth factor administration and the number of leukapheresis procedures. The search for the optimum methods of donor management may improve the acceptability of this procedure and increase the number of allogeneic transplantations from PBPCs.

Extensive studies have tested the clinical impact of double and triple sequential transplants as front-line therapy in MM, following the suggestion that dose escalation can overcome the marked drug resistance characteristic of this disease, but the superiority of such approaches vs one single transplant has still to be demonstrated. The aim of our study was to evaluate the feasibility and efficacy of high-dose idarubicine intensification of a standard busulphan-melphalan conditioning regimen in MM. Twenty-eight patients (median age 55 years) with sensitive disease received PBSCT after high-dose idarubicine combined with busulphan and melphalan and followed by s.c. rhG-CSF until PMN recovery. The most severe toxicity was represented by oral mucositis which resolved with hemopoietic reconstitution. Overall response and CR rate were 52% and 40%, respectively. Currently, 36 patients are alive and 19 are progression-free a median of 20 months (12-36) from transplant. The 3-year projected probability of progression-free survival for patients transplanted after first-line treatment is 60%. The combination of Ida/Bu/Melph appears a promising alternative regimen for PBSCT in myeloma, with low transplant-related toxicity and fast hematological recovery. Long-term follow-up and a prospective randomized study, now ongoing, will probably clarify whether an idarubicine-intensified regimen will result in superior outcomes to conventional conditioning and even be comparable to a double consecutive transplant program.

Authors expose their experience with autotransfusion, made during several years in a general surgery university department. Discussion is made about ethic and economical aspect of the philosophy guiding the most general concept of blood sparing, and different methods of autotransfusion; attention is then focused on practical experience made during two years (1995-1997) when the program worked well. On the whole, in 94 patients, 172 blood units were collected plus 10 plasma units obtained by aferesis. No method-related complications are have been observed. Elements who corresponded to difficulties or obstacles to the fully application of the method have been critically analyzed. Authors propose finally guide-lines which want to be valid proposal to increase method use while respecting at the best ethics, economics, efficacy and efficiency that must guide our work.

Background/aims: Autologous blood predonation is still not as widespread as it should be in general surgery practice, even if the method is well-known and has benefits established in international literature. Authors describe the impact of an autotransfusion program, in a general surgery university department, focusing on management and cost problems., Methodology: A description of the efficacy of the program during a yearlong activity period is presented. An analysis has been made about the quantity of predonated blood/plasma units, the quantity actually transfused and use of homologous blood. The problems which occurred and the cost are discussed., Results: The most used autotransfusion method was preoperative predeposit of autologous blood. The analysis of results focused on some organizational problems that need to be avoided in order to show the methods maximum benefits. In a large number of cases (some 50%) predeposit was not made because of several managing/technical problems. In another large number of cases (38%) the quantity of units predonated did not fully supply the needs and several patients received homologous products. In another number of cases predonated blood units were not used at all (61/34%)., Conclusions: Predeposit, preoperative hemodilution and intraoperative recovery, are methods that should all be available in a general surgery department to manage in the best way the single patients blood/plasma needs, reducing post-transfusion complication. To optimize the program and minimize waste some guidelines must be established, with the aim of a rational and correct use of the procedure. Despite the value of the method, and the favor encountered by the patients, we must not forget that the use of autologous blood is not costless.

Melanocortin peptides are known to be extremely potent in causing the sustained reversal of different shock conditions, both in experimental animals and humans; the mechanism of action includes an essential brain loop. Three melanocortin receptor subtypes are expressed in brain tissue: MC(3), MC(4,) and MC(5) receptors. In a volume-controlled model of hemorrhagic shock in anesthetized rats, invariably causing the death of control animals within 30 min after saline injection, the i.v. bolus administration of the adrenocorticotropin fragment 1-24 (agonist at MC(4) and MC(5) receptors) at a dose of 160 microg/kg i.v. (54 nmol/kg) produced an almost complete and sustained restoration of cardiovascular and respiratory functions. An equimolar dose of gamma(1)-melanocyte stimulating hormone (selective agonist at MC(3) receptors) was completely ineffective. The selective antagonist at MC(4) receptors, HS014, although having no influence on cardiovascular and respiratory functions per se, dose-dependently prevented the antishock activity of adrenocorticotropin fragment 1-24, with the effect being complete either at the i.v. dose of 200 microg/kg or at the i.c.v. dose of 5 microg/rat (17-20 microg/kg). We concluded that the effect of melanocortin peptides in hemorrhagic shock is mediated by the MC(4) receptors in the brain.

We report a study concerning 100 patients affected by essential thrombocythemia: 90 adult (age greater than 20 years) and 10 pediatric subjects. The diagnosis was made by chance (78%), because of hemorrhages (10%), thrombosis (9%), vasomotor symptoms (29%). In the adult group, single-agent chemotherapy was performed with good remission using pipobroman or interferon. Antiaggregant agents were used in all patients at diagnosis. During the clinical course only a few complications occurred.

This retrospective study, including 118 patients with acute lymphoblastic leukemia (ALL) aged greater than 15 years, with a minimum follow-up of 6 years, was aimed at defining potentially "cured" adults with ALL. At present, 21 out of 92 patients who achieved complete remission (CR) are long survivors: 16 in first CR, off-therapy; 4 in 2nd CR (3 off-therapy); 1 in 3rd CR, on treatment. On the basis of available data, we tried to identify factors at diagnosis which might predict long-term survival: white blood cell (WBC) count on admission was the only significant prognostic factor for overall survival (p = 0.0002) and first CR duration (p = 0.0005). The survival hazard rate (risk of death from acute leukemia per day) reaches 0 between 8 and 9 years from diagnosis. From our data we can identify two groups of ALL long-term survivors: the first includes 16 patients in 1st continuous CR (CCR), 12 of whom in CCR for over 8 years may be considered "cured"; the second group comprises 5 patients, relapsing once or twice, alive in 2nd or 3rd CR.