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Paolo Grossi

Publications and source records attributed to Paolo Grossi.

At least 19 recordsLinked to original sources

Kidney transplantation from anti-HBc+ donors: results from a retrospective Italian study.

BACKGROUND: The risk of transmitting a hepatitis B virus (HBV) infection from donor kidneys with a past HBV serological profile may be negligible. Data on HBV transmission to kidney transplant recipients from donor organs that were anti-HBc/HBsAg in Italy has not been previously reported. Anti-HBc testing in cadaver organ donors has been mandatory in Italy since 2002, when anti-HBc determinations were included in the National Guidelines for donor evaluation. Therefore, prior to that date kidney recipients from anti-HBc/HBsAg donors can be identified retrospectively where stored serum is available for testing. METHODS: The prevalence of anti-HBc Italian organ donors, the incidence of HBV transmission according to the recipients' HBV status (vaccinated, recovered, or naive), and the clinical impact (5-year graft and patient survival rates) in the North Italy Transplant program was evaluated by retrospectively screening for anti-HBc antibodies in the sera of cadaver kidney donors used in transplants from 1997 to 1999. RESULTS: Two hundred and ten donors were found to have been anti-HBc. At the time of the study, no active infection was observed in any of the 344 HBsAg recipients, but 4/140 (2.86%) of the vaccinated recipients were found to have been anti-HBc/HBsAg. None of these patients, however, had any biochemical or clinical history of HBV infection. Patient and graft survival rates of anti-HBc or anti-HBc kidney recipients did not differ statistically. CONCLUSION: Kidney grafts from anti-HBc donors should be considered in all recipients because the benefit obtained from the transplantation out weighs the negligible risk of HBV transmission.

Adolescent↗

Antifungal prophylaxis in liver transplant patients: a systematic review and meta-analysis.

We performed a meta-analysis to determine whether antifungal prophylaxis decreases infectious morbidity and mortality in liver transplant patients. We searched for randomized trials dealing with prophylaxis with systemic antifungal agents. We used a fixed effect model, with risk ratio (RR) and 95% confidence interval (CI); we assessed study quality for heterogeneity and publication bias. Six studies (5 double-blind), for a total of 698 patients, compared fluconazole, itraconazole, or liposomal amphotericin to placebo (5 studies) or oral nystatin. Prophylaxis reduced colonization (RR, 0.45; CI, 0.37-0.55), total proven fungal infections (RR, 0.31; CI, 0.21-0.46), which included both superficial (RR, 0.27; CI, 0.16-0.45) and invasive (RR, 0.33; CI, 0.18-0.59) infections, and mortality attributable to fungal infection (RR, 0.30; CI, 0.12-0.75). Prophylaxis did not affect overall mortality (RR, 1.06; CI, 0.69-1.64) or empiric treatment for suspected fungal infection (RR, 0.80; CI, 0.39-1.67). The beneficial effect of antifungal prophylaxis was predominantly associated with the reduction of Candida albicans infection and mortality attributable to C. albicans. Compared to controls, however, patients receiving prophylaxis experienced a higher proportion of episodes of non-albicans Candida, and in particular of C. glabrata. No beneficial effect on invasive Aspergillus infection was observed. In conclusion, our analysis shows a clear, though limited, beneficial effect of antifungal prophylaxis in liver transplant patients. Concerns about the selection of triazole-resistant Candida strains, however, are realistic, and the potential disadvantages of prophylaxis should be weighed against the established benefits.

Antifungal Agents↗

Infections after living-donor liver transplantation.

BACKGROUND: Despite greater awareness of organ donation among the general public, the supply of cadaveric organs has fallen short of identified needs. Living-donor liver transplantation (LDLT) is an effective means of overcoming the shortage of adult organs, as outcomes are now comparable to those of cadaveric donor liver transplantation. METHODS: From January, 2002 through January, 2006, 40 LDLTs were performed at our center. With two exceptions, the donor was a first-degree relative of the recipient; all donors were in excellent health with good hepatic function and morphology. All but two donors contributed the right lobe. Infections in the donors and recipients were analyzed. RESULTS: Clinically relevant infections occurred in three donors. In the recipients, the infections did not differ significantly from those experienced by recipients of cadaveric organs in terms of risk factors (e.g., poor graft function, re-transplantation, surgical complications such as bile duct stenosis, or vascular anastomotic stenosis) or type of infection. Cholangitis was the most frequent infection, leading to septic shock in five of the 14 patients with infections; intra-abdominal infections related to surgical complications led to septic shock in three additional patients. The other most commonly observed infections were urinary tract infections (n=10) and pneumonia (n=3). CONCLUSIONS: Living-donor liver transplantation offers hope to patients with end-stage liver disease in geographic areas where the waiting time mortality is high and available organs from deceased donors fall short of the population's need.

Abdominal Abscess↗

Antimicrobial treatment of sepsis.

BACKGROUND: Sepsis is a major cause of morbidity and death in hospitalized patients worldwide and one of the largest current challenges in critical care. METHOD: Review of the pertinent English-language literature. RESULTS: Treatment goals conventionally have included maintenance of systemic perfusion and eradication of sources of infection. Initial empiric antimicrobial regimen should be broad enough to cover all likely pathogens, as there is little margin for error in critically ill patients. CONCLUSION: A multidisciplinary team, including the critical care physician, the microbiologist, the infectious disease specialist, the surgeon, and the clinical pharmacologist, is necessary for optimal patient outcome.

Adult↗

Treatment of Pseudomonas aeruginosa infection in critically ill patients.

Critically ill patients are on the increase in the present clinical setting. Aging of our population and increasingly aggressive medical and therapeutic interventions, including implanted foreign bodies, organ transplantation and advances in the chemotherapy of malignant diseases, have created a cohort of particularly vulnerable patients. Pseudomonas aeruginosa is one of the leading gram-negative organisms associated with nosocomial infections. This organism is frequently feared because it causes severe hospital-acquired infections, especially in immunocompromised hosts, and is often antibiotic resistant, complicating the choice of therapy. The epidemiology, microbiology, mechanisms of resistance and currently available and future treatment options for the most relevant infections caused by P. aeruginosa are reviewed.

Anti-Bacterial Agents↗

Failure of levofloxacin treatment in community-acquired pneumococcal pneumonia.

BACKGROUND: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP). High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins). Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy. CASE PRESENTATION: A 72-year-old patient with long history of chronic obstructive pulmonary disease and multiple fluoroquinolone treatments for recurrent lower respiratory tract infections developed fever, increased sputum production, and dyspnea. He was treated with oral levofloxacin (500 mg bid). Three days later, because of acute respiratory insufficiency, the patient was hospitalized. Levofloxacin treatment was supplemented with piperacillin/tazobactam. Microbiological tests detected a S. pneumoniae strain intermediate to penicillin (MIC, 1 mg/L) and resistant to macrolides (MIC >256 mg/L) and fluoroquinolones (MIC >32 mg/L). Point mutations were detected in gyrA (Ser81-Phe), parE (Ile460-Val), and parC gene (Ser79-Phe; Lys137-Asn). Complete clinical response followed treatment with piperacillin/tazobactam. CONCLUSION: This is the first Italian case of community-acquired pneumonia due to a fluoroquinolone-resistant S. pneumoniae isolate where treatment failure of levofloxacin was documented. Molecular analysis showed a group of mutations that have not yet been reported from Italy and has been detected only twice in Europe. Treatment with piperacillin/tazobactam appears an effective means to inhibit fluoroquinolone-resistant strains of S. pneumoniae causing community-acquired pneumonia in seriously ill patients.

Aged↗

Successful medical treatment of multiple brain abscesses due to Nocardia farcinica in a paediatric renal transplant recipient.

Brain abscesses caused by Nocardia are rare, but it is very important to detect and treat them early because the associated mortality is 3 times higher than that associated with other bacterial brain abscesses. This infection is prevalent among adults on long-term immunosuppressive therapy; we report the case of a male kidney transplant recipient aged 12.7 years who developed early multiple Nocardia-induced brain abscesses that were successfully treated with linezolid, a novel antibiotic therapy.

Acetamides↗

Interruption of highly active antiretroviral therapy in HIV clinical practice: results from the Italian Cohort of Antiretroviral-Naive Patients.

OBJECTIVES: To investigate the frequency of a first therapy interruption (TI) > or = 12 weeks, to identify the factors associated with TI and with therapy resumption, and to compare the risk of developing clinical events during TI and during continuous therapy. METHODS: Observational study of 3142 patients who started a first highly active antiretroviral therapy (HAART) regimen. End points were time to (1) first TI of > or = 12 weeks, (2) subsequent therapy resumption, and (3) development of new AIDS-related events or death. RESULTS: Over a median follow-up period of 41 months (interquartile range: 18-60 months), 721 patients (22.9%) interrupted HAART for > or = 12 weeks, with a probability of 28.6% (95% confidence interval [CI]: 26.7-30.6) by 4 years from the date of therapy initiation. Patient decision (47.4%) and toxicity (24.0%) were the main reasons for TI. Women, injection drug users, and patients with a higher current CD4 cell count were more likely to interrupt. The median time to therapy resumption was 12 months (95% CI: 11-14). The higher the current CD4 count, the slower was the rate of resuming therapy; conversely, patients who stopped because of failure and those with a pre-HAART viral load >100,000 copies/mL resumed therapy sooner. Two hundred eighty-one patients experienced clinical progression at a rate of 2.6 per 100 person-years (pys) (95% CI: 2.3-3.0) while patients were on therapy and 3.5 per 100 pys (95% CI: 2.4-4.8) during TI. The adjusted relative hazard of clinical progression associated with TI was 2.75 (95% CI: 1.14-6.65; P = 0.03). CONCLUSIONS: TI occurring in clinical practice is associated with an increased risk of clinical progression; hence, it should be discouraged outside strictly experimental settings.

Adult↗

Continuous peripheral nerve blocks: state of the art.

PURPOSE OF REVIEW: This review was performed through a Medline research to evaluate articles published between January 2004 and April 2005. Technical procedures, indications, drugs, infusion regimens, and complications of continuous peripheral nerve blocks were considered. RECENT FINDINGS: A total of 27 articles were reviewed. With respect to technical procedures, the authors focused on advantages of stimulating catheters or ultrasound guidance. With the help of these techniques, a correct catheter placement as close to the targeted nerve as possible was obtained. The total amount of local anesthetic administered was thereby reduced. Using ultrasound needle guidance, the spread of local anesthetic around the nerve could be visualized. Articles dealing with the choice of local anesthetic showed equianalgesia and equipotency of continuous perineural infusion of levobupivacaine 0.125% and ropivacaine 0.2%. The best infusion regimen for postoperative analgesia appears to be a combination of a preset basal rate administered together with small bolus doses in almost all continuous peripheral nerve blocks. Overall, complications such as infections, local anesthetic toxic plasma levels, hematoma formation, or nerve injury seem to be rare in continuous peripheral nerve blockade. SUMMARY: Continuous peripheral nerve blockade is an effective and safe technique for postoperative analgesia, even when administered at home. To optimize this technique, further studies are needed to help minimize the risk of side effects, improve techniques to locate the targeted nerve (stimulating catheters or ultrasound imaging) and choose less toxic drugs (levobupivacaine and ropivacaine) with more effective infusion regimens.

Journal Article↗

Strategies for evaluation of suitable donors: Italian experience.

Italy was lacking standardised procedures for donor safety evaluation. We developed practice guidelines, while a panel of experts coordinated by the National Transplant Centre, is available 24 hours a day to support decisions in difficult cases. The guidelines identify five levels of risk and give recommendations for the utilization of donors with HBV and HCV infections as well as for malignancies with negligible or very low risk of transmission. In conclusion we aim to standardize the process of donor evaluation across Italy, to increase the pool of utilised donors and to reduce the risk of communicable disease transmission.

Humans↗

Aspergillus left ventricular assist device endocarditis.

Left ventricular assist device (LVAD) support is an established therapy for patients with end-stage heart failure as a bridge to transplant; its usage as an alternative for those patients not eligible for transplant is not an established therapy yet. A 68-year-old male had a Thoratec-Heartmate LVAD implanted as destination therapy. After an uneventful (apart from early fever) recovery in the intensive care unit, the patient developed an intractable high temperature, and generalized sepsis and died 21 days following implant. The white cell blood count never exceeded the guard limits, and the patient succumbed with severe LVAD valve malfunction. At post-mortem examination friable material consisting of fungal hyphae was found on the inflow and outflow valves. According to published clinical trials, infection accounts for more than 40% of mortality in LVAD supported patients. Fungal LVAD endocarditis is a particularly deadly disease. Successful management requires a high level of suspicion and timely institution of antifungal therapy to control the infection. This has led some authors to recommend empiric antifungal therapy in LVAD recipients with culture-negative sepsis unresponsive to broad-spectrum antibiotics.

Aged↗

Human cytomegalovirus pp67 mRNAemia versus pp65 antigenemia for guiding preemptive therapy in heart and lung transplant recipients: a prospective, randomized, controlled, open-label trial.

BACKGROUND: Preemptive therapy of human cytomegalovirus (HCMV) infections has gained popularity in transplantation centers. However, standardized protocols are not available. In particular, whether a qualitative molecular assay for detection of a late (pp67) HCMV mRNA represents a valuable alternative to quantitative antigenemia remains to be defined. METHODS: Overall, 82 heart (HTR) and lung (LTR) transplant recipients were randomized into two arms, where therapy was guided by qualitative pp67 mRNA NASBA (40 patients) or quantitative antigenemia (42 patients). In the NASBA arm, both primary and recurrent infections were treated upon first confirmed positive NASBA result. In the antigenemia arm, primary infections were treated upon first confirmed positive result, while recurrent infections were treated upon cutoff of 100 pp65-positive leukocytes. In both arms, therapy was stopped upon virus disappearance. Primary endpoint was duration of therapy. RESULTS: The number of treated/infected patients was significantly higher in the NASBA arm (25/30 vs. 15/39; P=0.015), as was the number of treated/relapsing patients (5/8 vs. 1/11; P=0.040), whereas the number of HCMV-infected/total number of patients was significantly higher in the antigenemia arm (39/42 vs. 30/40; P=0.026). Thus, in the NASBA arm, although the median duration of therapy was shorter compared to antigenemia (17 vs. 21 days, P>0.05), the overall number of days of therapy was significantly higher. No patient developed HCMV disease. CONCLUSION: pp67 mRNA NASBA can safely replace antigenemia, with some apparent advantages (semiautomation and objectivity of test results) and disadvantages (overtreatment of patients and greater duration of overall treatment).

Adult↗

Peripheral nerve blocks for anaesthesia and postoperative analgesia.

PURPOSE OF REVIEW: Perioperative analgesia is a major concern for the patient and for the anesthesiologist, whose task is to avoid pain and all related complications on immediate outcome and healing. Regional anesthesia, alone or combined with general anesthesia, is becoming a preferred technique in a variety of surgical procedures. There is increasing interest in peripheral nerve blocks, single or continuous, mainly for perioperative treatment of unilateral surgery. Specificity of analgesic area combined with decreased complications, including spinal or epidural hematoma, urinary retention, or hemodynamic alterations, are advantages of the peripheral nerve block over more central neural blocks. RECENT FINDINGS: Insertion of catheters near neural plexuses or in the vicinity of single nerves are being continuously developed and improved. The appearance of new techniques and devices is increasing. Percutaneous electrode guidance, ultrasonographic localization of neural structures, and the use of stimulating catheters represent the newest advances in this area. Use of enantiomeric local anesthetic drugs permits a safer and wider range of postoperative treatment, which includes continuous analgesia administered in the patient's home. Use of patient-controlled analgesia, through electronic or elastomeric pumps, is recommended for postoperative pain control. Peripheral nerve block is the standard for anesthesia or analgesia in ambulatory surgery. Complications of the technique have been examined in large clinical studies which have recently been published. Results of such studies highlight the effectiveness and safety of peripheral blocks. These results have given new strength to arguments for regional anesthesia and analgesia and led to the increase in popularity of regional techniques. The articles considered below have, in summary, the main purpose of enhancing safety, as well as dissemination and education regarding regional anesthetic techniques. SUMMARY: Possibilities afforded by the use of peripheral nerve blocks mainly consist of prolonged analgesia, selective area of action, and fewer collateral effects when compared with general anesthesia or more central neural blockade. Introduction of new devices and new techniques are increasing, as evidenced by the large number of studies which have appeared in the literature during the past year.

Journal Article↗

Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication.

Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorders (PTLDs) are a well-recognized complication of immunosuppression in solid organ transplant recipients. The reported therapeutic approaches are frequently complicated by rejection, toxicity, and other infectious pathologies, and overall mortality in patients with unresponsive PTLD remains high. Thus, low-toxicity treatment options or, preferably, some form of prophylactic/preemptive intervention are warranted to improve PTLD outcome in this setting. We assessed whether transfer of EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from the peripheral blood of allograft recipients receiving immunosuppression could increase EBV-specific killing in vivo without augmenting the probability of graft rejection. Autologous EBV-specific CTLs were generated for 23 patients who were identified as being at risk of developing PTLD through the finding of elevated EBV DNA load. Of the 23 patients, 7 received 1 to 5 infusions of EBV-specific CTLs. CTL transfer was well tolerated, and none of the patients showed any evidence of rejection. An increase of the EBV-specific cytotoxicity was observed after infusion, notwithstanding continuation of immunosuppressive therapy. EBV DNA levels had a 1.5- to 3-log decrease in 5 patients, whereas in the other 2 graft recipients CTL transfer had no apparent stable effect on EBV load. Our data suggest that the infusion of autologous EBV-specific CTLs obtained from peripheral blood mononuclear cells recovered at the time of viral reactivation is able to augment virus-specific immune response and to reduce viral load in organ transplant recipients. This approach may, therefore, be safely used as prophylaxis of EBV-related lymphoproliferative disorders in these patients, following a strategy of preemptive therapy guided by EBV DNA levels.

CD3 Complex↗

Adoptive Transfer of Herpesvirusspecific Cytotoxic T Lymphocytes in Transplant Recipients.

Profound suppression of T-cell immunity observed after transplantation may permit the emergence of life-threatening viral complications. Prevention or treatment of viral infections in immunocompromised patients through the infusion of small numbers of antigen-specific T-cell lines or clones is the most successful example of adoptive immunotherapy in humans. In fact, adoptive transfer of T cells of donor origin has been demonstrated to be able to restore protective immunity towards these infectious agents and to control established disease. This article reviews human trials of adoptive immunotherapy for herpesvirus-related complications, with the aim of defining principles and problems encountered so far to aid the design of future clinical studies.

Journal Article↗

Use of sequential electrical nerve stimuli (SENS) for location of the sciatic nerve and lumbar plexus.

BACKGROUND AND OBJECTIVES: Conventional electrical stimulation has been done by continuous adjustment of current amplitude at a single, set pulse duration (conventionally, 0.1 ms). This study evaluated a novel technique for nerve location by utilization of a peripheral-nerve stimulator (PNS) programmed to deliver sequential electrical nerve stimuli (SENS). A repeating series of alternating sequential pulses of 0.1, 0.3, and 1.0 ms at 1/3-second period intervals between pulses were generated so that at a greater distance from the nerve, only higher-duration pulses would stimulate the targeted nerve and result in 1 or 2 motor responses (MR) per second. Three MR per second at 0.5 mA or less signified the conventional endpoint for nerve location (</=0.5 mA, 0.1 ms) because that value indicated that the 0.1-ms pulse was effective. The conventional 0.1-ms pulse served as a built-in control to which the SENS was compared. METHODS: Sixteen sciatic/psoas blocks were performed on 8 patients. Nerve location was by SENS, with an 80-mm block needle. Needle advance began at 1.0 mA until MR. If 1 or 2 MR/s occurred, the needle was advanced until 3 MR/s were obtained. When 3 MR/s occurred at 0.5 mA or less, needle position was fixed (final position), and mA further decreased until MR disappeared. Two digital video cameras separately recorded needle depth and MR for analysis. Final needle position was designated as zero, and distance was calculated relative to it. RESULTS: In 12 of 16 of the performed blocks, SENS resulted in advanced notification (1 or 2 MR/s), which yielded additional visual feedback compared with control before final nerve location and, thus, increased range. In 15 of 16 blocks, MR did not disappear, once elicited, through final needle location. CONCLUSIONS: SENS resulted in increased sensitivity without compromising specificity of nerve location.

Adult↗