CD3+ graft cell count influence on chronic GVHD in haploidentical allogeneic transplantation using post-transplant cyclophosphamide.

The effects of graft or donor characteristics in haploidentical hematopoietic cell transplantation (HCT) using post-transplant cyclophosphamide (PT-Cy) are largely unknown. In this multicenter retrospective study we analyzed the correlations between graft cell composition (CD34+, CD3+) and donor features on transplant outcomes in 234 patients who underwent HCT between 2010 and 2016. On multivariate analysis, the use of peripheral blood stem cells (PBSC) was associated with an increased incidence of grade 2-4 acute GVHD [HR 1.94, 95% confidence Interval (CI) = 1.01-3.98, p = 0.05]. An elevated CD3+ graft content was associated with an increased incidence of all-grade chronic GVHD [HR 1.36 (95% CI = 1.06-1.74), p = 0.01]. This effect was confirmed only for the PBSC graft group. A higher CD34+ graft content had a protective role on non-relapse mortality [HR 0.78 (95% CI = 0.62-0.96), p = 0.02] but this was confirmed only for the bone marrow (BM)-derived graft cohort. Donor characteristics did not influence any outcomes. GVHD prophylaxis should be modulated accordingly to CD3+ graft content, especially when a PBSC graft is used. These results need further validation in prospective trials.

Allogeneic stem cell transplantation and subsequent treatments as a comprehensive strategy for long-term survival of multiple myeloma patients.

We evaluated 71 patients treated with allogeneic hematopoietic cell transplantation (allo-HCT) for multiple myeloma (MM). Forty-three patients (61%) received allo-HCT after the first line of therapy. Fifty-eight patients (82%) had chemosensitive disease at the time of allo-HCT. A HLA-matched related or unrelated donor was available for 68 patients (96%). Non-myeloablative or reduced-intensity conditioning regimen and peripheral blood hematopoietic cells as a graft source were used in most patients. The cumulative incidence of grade II-IV acute GVHD at day +100 and chronic GVHD at 5 years was 13% (95% CI 7-23%) and 35% (95% CI 24-46), respectively. Non-relapse mortality and relapse/progression incidence at 5 years were 12% (95% CI 5-23) and 65% (95% CI 49-76), respectively. With a median follow-up in survivors of 100 months (range 16-186), the 5-year PFS and OS were 39% (95% CI 27-52) and 60% (95% CI 55-77), respectively. On multivariate analysis: age >55 years was associated with both a reduced PFS (RR 2.11, 95% CI 1.15-3.87) and OS (RR 5.53, 95% CI 2.22-13.76); chemorefractory disease at allo-HCT was associated with both reduced PFS (RR 3.09, 95% CI 1.37-7.00) and OS (RR 3.19, 95% CI 1.23-8.22). At relapse, 24 patients (56%) received bortezomib, 28 (65%) lenalidomide, 11 (26%) pomalidomide, 16 (37%) donor lymphocytes infusion as part of salvage therapy after allo-HCT relapse. Median PFS from time of salvage treatment was 7 months (range 0-113 months) for bortezomib-based therapy, 14 months (range 0-79 months) for lenalidomide and 10 months (range 1-28) for pomalidomide. Allo-HCT is a feasible and effective strategy in selected patients with MM and could be an effective platform for subsequent therapies.

Erectile dysfunction in 1050 men following extended (18 cores) vs saturation (28 cores) vs saturation plus MRI-targeted prostate biopsy (32 cores).

Erectile dysfunction (ED) following transperineal prostate biopsy (TPB) was prospectively evaluated. From January 2011 to January 2014, 1050 patients were submitted to TPB: 18 core (extended TPB) in 610 cases, 28 core (saturation TPB) in 360 cases and 32 core (saturation plus magnetic resonance imaging (MRI) targeted TPB) in 210 cases. The indications for biopsy were increasing prostate-specific antigen (PSA) or PSA>10 ng ml(-1). All patients were prospectively evaluated with the 5-item version of the International Index of Erectile Function (IIEF-5) at time zero and at 1, 3 and 6 months from TPB. Prostate cancer was diagnosed in 385/1050 (36.6%) patients; 560 men (350 vs 110 vs 100) having benign histology and normal sexual activity also completed the study. Overall, IEEF-5 score at time zero and at 1, 3 and 6 months did not significantly worsen (P>0.05); in detail, at 1 month from biopsy 15 extended TPB (4.2%) vs 7 saturation TPB (6.4%) vs 7 saturation plus MRI targeted TPB (7%) men referred mild ED that disappeared after 3 months. Irrespective of method (18 vs 28 vs 32 core) TPB did not significantly worsen erectile function at 3-6 months from the procedure.

Carcinosarcoma of the Female Urethra.

Carcinosarcoma is a rare malignant tumor with a biphasic morphology characterized by the presence of a malignant epithelial and mesenchymal component. It has been reported in many organs, including the genitourinary tract. We describe a case of a 47-year-old woman admitted to our hospital for history of recurrent urinary tract infection, dysuria and discharge of bloody fluid from the urethra at the end of urination. A tender palpable mass under the anterior vaginal wall was found and pathological examination showed a urethral carcinosarcoma. The histopathogenetic hypothesis and clinical management were considered in this report.

Analytical approaches to the diagnosis and treatment of aging and aging-related disease: redox status and proteomics.

Basal levels of oxidants are indispensible for redox signaling to produce adaptive cellular responses such as vitagenes linked to cell survival; however, at higher levels, they are detrimental to cells, contributing to aging and to the pathogenesis of numerous age-related diseases. Aging is a complex systemic process and the major gap in aging research reminds the insufficient knowledge about pathways shifting from normal "healthy" aging to disease-associated pathological aging. The major complication of normal "healthy" aging is in fact the increasing risk of age-related diseases such as cardiovascular diseases, diabetes mellitus, and neurodegenerative pathologies that can adversely affect the quality of life in general, with enhanced incidences of comorbidities and mortality. In this context, global "omics" approaches may help to dissect and fully study the cellular and molecular mechanisms of aging and age-associated processes. The proteome, being more close to the phenotype than the transcriptome and more stable than the metabolome, represents the most promising "omics" field in aging research. In the present study, we exploit recent advances in the redox biology of aging and discuss the potential of proteomics approaches as innovative tools for monitoring at the proteome level the extent of protein oxidative insult and related modifications with the identification of targeted proteins.

Osteoblastoma of cervical spine causing an unusual neck pain.

Osteoblastoma is a rare benign tumor of bone that accounts for approximately 1% of primary skeletal neoplasms, with around 90% of cases diagnosed in the second and third decades of life. Cervical spine is an usual localization of osteoblastoma. The main clinical manifestation in case of cervical spine location is a progressive and resistant pain, possibly accompanied by stiffness, scoliosis or other ailments, including severe neurological deficits. Owing to a non-specific clinical presentation of osteoblastoma, the delay in diagnosis is common. Osteoblastomas may have an aggressive behavior, tend to enlarge and damage the bone and adjacent structures. The treatment of choice is, therefore, a wide and complete surgical excision of the lesion in order to achieve full recovery and prevent recurrence or, in some cases, malignant transformation. In the case of persistent neck pain, not readily relieved by aspirin and possibly accompanied by stiffness, scoliosis or neurological deficits, especially in young subjects, osteoblastoma of cervical spine may be one of the diagnostic options to be considered, in order to avoid delay in diagnosis. We report the case of a 41-year-old male affected by cervical spine osteoblastoma causing a lasting neck pain.

Chest pain caused by tracheostomy tube malposition: the importance of choosing the right tube.

We describe a case of chest pain caused by tracheostomy tube malposition in a 65-year old woman with chronic respiratory failure due to chronic obstructive pulmonary disease. This report highlights the importance of the correct choice of tracheostomy tube devices for mechanically ventilated and/or spontaneously breathing patients.

Power Doppler ultrasonography with time-signal intensity curves in monitoring hepatocellular carcinoma and liver metastases after intralesional therapy.

PURPOSE: Analysis of time-intensity curves allows evaluation of the patterns of lesion enhancement before and after treatment. The aim of this study was to evaluate the diagnostic accuracy of time-intensity curves in monitoring intralesional therapy of focal hepatic lesions. MATERIALS AND METHODS: Twenty patients underwent intralesional therapy with either radiofrequency thermal ablation or percutaneous ethanol injection. Contrast-enhanced power Doppler ultrasound with analysis of time-intensity curves was performed one day before and one day after treatment. Targeted biopsy was then obtained to confirm the imaging findings. RESULTS: Before treatment, all lesions showed time-intensity curves characterised by high peaks of signal intensity and plateaus. Complete tumour necrosis, confirmed by targeted biopsy, was observed in patients showing no intralesional flow signals and time-intensity curves with low peak of signal intensity and absence of plateau after treatment. Biopsy confirmed the presence of residual neoplastic tissue in one patient exhibiting perilesional vascularity, absence of intralesional flow signals, and a time-intensity curve with high peak of signal intensity and plateau. CONCLUSIONS: According to our findings, time-intensity curves characterised by high peak of signal intensity and plateau might reflect the presence of perilesional or intralesional neoplastic tissue and provide important information on the effectiveness of the treatment.

Efficacy of the treatment of dogs with leishmaniosis with a combination of metronidazole and spiramycin.

Twenty-seven dogs infected naturally with Leishmania infantum were used in a randomised controlled trial to compare the clinical and parasitological efficacy of an oral treatment with a combination of metronidazole and spiramycin (13 dogs) with the efficacy of conventional treatment with meglumine antimonate and allopurinol (14 dogs) as controls. In the test group one dog had to be withdrawn from the treatment because it developed pemphigus foliaceus; 10 of the dogs were clinically responsive but none was cured parasitologically. In the control group four dogs were withdrawn from the treatment because of side effects; eight of the dogs were clinically responsive but none was cured parasitologically. The control group showed signs of improvement after an average of 30 days, whereas the test group did not show signs of improvement until after an average of 45 days.

Isolated local recurrence of renal neoplasm with caval involvement 16 years after radical nephrectomy.

OBJECTIVE: To report a case of local recurrence 16 years after radical nephrectomy; to analyse literature data concerning, treatment and prognosis. METHODS/RESULTS: We report a case of local recurence associated with caval trombosis who was underwent an en-bloc resection of vena cava along with pericaval lesion and caval replacement with PTFE prosthesis. The Authors reviewed and analysed literature data. CONCLUSIONS: Local recurrence after radical nephrectomy is rare as it is reported only in 2-4% of patients. This condition is even rarer beyond 10 years especially if associated with caval trombosis. A case of isolated local recurrence of renal cell carcinoma with caval involvement 16 years after radical nephrectomy is described herein. To the best of our knowledge, this is the first case reported in literature. This case highlights the opportunity of a periodic checkup of patients submitted to radical nephrectomy, even many years after surgery.

[Male cervico-urethral obstruction of organic cause: transrectal prostatic ultrasonography versus permicturition and urethral ultrasonography]. / Ostruzione cervico-uretrale maschile da causa organica: ecografia prostatica transrettale versus eco perminzionale ed uretrale.

AIM: This paper reports personal experience relating to the use of "static" and "permicturition" prostatic transrectal ultrasonography and urethral ultrasonography in the imaging diagnosis of obstructed patients. METHODS: Between January 1996 and January 1998 we selected 96 consecutive patients aged between 25 and 73 years old (mean 54 years) with symptoms of obstructive dysuria with pathological uroflowmetry and pressure/flow rates (Qmax ranging between 5-12 ml/sec and URA between 34-81). Eighteen of the patients selected had previously undergone prostate surgery for benign pathologies. All patients underwent a standard and permicturition transrectal ultrasonography and urethral ultrasonography using a retrograde approach. The results were compared with those obtained by retrograde urethrocystography and urethrocystoscopy, regarded as the "gold standard" for the diagnosis of urethral obstruction. RESULTS: Sixty-three (65.5%) patients were able to execute the permicturition phase, but only 54 (56.2%) reported that the test was indicative of "real urination", whereas retrograde urethral ultrasonography was well tolerated in all cases and easy to accomplish. In 19 (20%) patients (6 of whom had undergone prostate surgery and 13 were suffering from urethral stenosis), "major" organic alterations responsible for urethral obstruction were observed with the combined use of these ultrasonographic methods. These were not evident using static transrectal ultrasonography and increased the diagnostic sensitivity from 80 to 98%. CONCLUSIONS: We feel that an increasingly complete ultrasonographic study of the lower urinary tract is necessary, above all in obstructed patients. This can be achieved using permicturition and urethral transrectal ultrasonography, ensuring an accurate diagnosis and optimising health expenditure.

Protein degradation and apoptotic death in lymphocytes during Fiv infection: activation of the ubiquitin-proteasome proteolytic system.

The movement of a cell through the sequential phases of apoptosis is accompanied by a progressive decrease in cell size with loss in protein mass. In lymphocytes from Hiv-infected persons, protein loss during apoptosis is due to increased protein degradation rather than decreased synthesis. To identify and characterize the proteolytic enzymes or enzyme systems involved in this process, we studied several features of protein turnover in lymphocytes from peripheral blood and lymph nodes during the natural and experimental infection by feline immunodeficiency virus (Fiv). This animal model allowed us to integrate in vivo results with in vitro observations of protein damage. Here we report that protein breakdown in apoptotic cells is concomitant with the activation of the ATP and ubiquitin-dependent multicatalytic system (proteasome). We suggest that proteasome activation is part of the proteolytic cascade in the execution phases of apoptosis in AIDS.

[Target controlled infusion (TCI): applications of the "TCI visual" program in anesthesia and sedation with propofol]. / Target controlled infusion (TCI): applicazione del programma "visual TCI" all'anestesia ed alla sedazione col propofol.

BACKGROUND: Systems for Target Controlled Infusion accepting not only patient' data, like Diprifusor, but also a pharmacokinetic model have not been available in Italy in the last years. Therefore a program which controls a Pilot Anesthesia Vial pump and accepts any pharmacokinetic model was developed and applied to propofol infusion for anaesthesia and sedation. METHODS: Two versions of the Visual TCI program have been developed. The first, at intervals, supplies the anaesthetist with the values for the pump; the second directly interacts with the pump. The program also supplies the anaesthetist with the current amount of drug in each compartment and with the estimated awakening time. DESIGN: preliminary prospective study. SETTING: operatory theatre and Intensive Care Unit in a University Hospital. PATIENTS: 6 patients undergoing total intravenous anaesthesia with propofol and fentanyl for abdominal surgery; 6 patients undergoing sedation with propofol in an Intensive Care Unit (the first 4-hour period was taken into account). INTERVENTIONS: propofol infusion was regulated by the Visual TCI program. The first version was employed in three patients of each group and the second one in the others. Hypo- and hypertensive episodes (systolic pressure less than 80 mmHg or higher than basal value plus 25%) were recorded during anaesthesia and sedation. Propofol concentration was measured in plasma three times at defined intervals and per cent differences between measured and computer-calculated values (Predictive error, PE) were calculated. RESULTS: No hypo- or hypertensive episodes were recorded. PE was 27.4 +/- 17.9%. CONCLUSIONS: The program was easily employed, caused no inconvenience, and its use was associated with a remarkable cardiovascular stability. PE distribution was acceptable on the ground of the criteria reported in the literature. The program can be applied to drugs other than propofol, with both two and three compartment pharmacokinetic models and the anaesthetist can choose the most suitable model for the patient.