SIAARTI guidelines for safety in locoregional anaesthesia.
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Anesthesia, Conduction↗
Biomedical subjects
P Grossi
Publications and source records attributed to P Grossi.
Liver transplantation in HIV-positive individuals: a new paradigm.
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Antiretroviral Therapy, Highly Active↗
Predicting the maximum-tolerated dose of PNU-159548 (4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin) in humans using CFU-GM clonogenic assays and prospective validation.
A haematotoxicity model was proposed by Parchment in 1998 to predict the maximum-tolerated dose (MTD) in humans of myelosuppressive antitumour agents by combining data from in vitro clonogenic assays on haematopoietic progenitors and in vivo systemic exposure data in animals. A prospective validation of this model in humans was performed with PNU-159548, a novel agent showing selective dose-limiting myelosuppression in animals. PNU-159548 and its main metabolite, PNU-169884, were tested in vitro on murine, canine and human colony forming units-granulocyte macrophages (CFU-GM) and in vivo on mice and dogs. The IC(90x) ratios (IC(x)=concentration inhibiting x% of colony growth) for CFU-GM and drug plasma protein binding were used to adjust the target plasma concentrations versus time curve (AUC) and predict the human MTD. The predicted MTD was compared with values achieved in phase I studies. Canine CFU-GM were 6-fold more sensitive (P<0.01) and murine CFU-GM 1.7-fold less sensitive (P<0.05) to PNU-159548 treatment than the human progenitors. PNU-169884 behaved similarly to PNU-159548. The predicted MTDs in humans calculated from data in mice and dogs were 15 and 38 mg/m(2), respectively. Overall, 61 patients were treated in two phase I studies, at doses ranging from 1.0 to 16 mg/m(2). Thrombocytopenia was dose-limiting with a MTD of 14 and 16 mg/m(2) in heavily and minimally pretreated/non-pretreated patients, respectively. Adjusting animal MTD data by means of the CFU-GM ratio between species can predict the human MTD with a good quantitative accuracy. Inhibition of common haemopoietic progenitors by PNU-159548 induced neutropenia/thrombocytopenia in animals and thrombocytopenia in patients, probably due to the higher sensitivity to the compound observed in human colony forming units-megakaryocyte (CFU-MK).
Animals↗
Prevalence and outcome of hepatitis B virus (HBV) infection following thoracic organ transplantation.
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Journal Article↗
[Brachial plexus block. The anaesthetic line is a guide for new approaches].
Brachial plexus blockade is one of the most widespread technique in regional anaesthesia. Many Authors presented different approaches to the plexus, following different routes, over or under the clavicle related to near landmarks, paresthesia or electrical nerve stimulation. The Author presents an anatomical perspective to guide the localization of the brachial plexus, following an anaesthetic line created by linking together several landmarks, generally used in few number for single approach techniques, over or under the clavicle. The line leaves from the apex of the scalene triangle, through the middle point of the clavicle, the middle point between the coracoid process and the chest profile, and arrives to the pulsation of the axillary artery, when the arm is abducted at 45 degrees. This general view favours a better understanding of the placement of the brachial plexus, following the anatomical guide developed from the anaesthetic line; thus the placement of the needle, from distal to proximal, in a vertical or tangential route towards the nerve structures becomes clearer, showing the different entry point in a simple and efficacious way. The same technique may apply to the infraclavicular approach, favouring the vertical approach or a tangential one, when catheterisation is needed.
Brachial Plexus↗
[Continuous brachial plexus blockade for shoulder surgery].
Continuous brachial plexus block is the technique of choice for postoperative shoulder pain treatment. The localization of the plexus is usually obtained drawing landmarks on the skin and using the electrical nerve stimulator; these and other different modalities are applied in order to reach safely and precisely nerve roots to be blocked with an anaesthetic solution. The Author presents a new anatomical perspective to guide the localization of the brachial plexus. It is shown how it is possible to detect the pathway of the brachial plexus from the cutaneous surface, linking between each other various landmarks: a) the apex of the scalene triangle, at the cross of a line leaving from the cricoid process and directed posterior to the posterior border of the sternocleidomastoid muscle, b) the midline of the clavicle c)the deltoid-pectoral sulcus d) the midpoint between the coracoid process and the chest profile e) the pulsation of the artery in the axylla. Following the guide of the so formed anesthetic line, is possible to place the needle, with a direction from distal to proximal, in a tangential route towards the interscalenic groove, thus allowing to perform a block of the plexus in a simple and efficacious way.
Brachial Plexus↗
[Peripheral blocks for the lower limb: lumbar plexus].
BACKGROUND: The techniques of continuous peripheral blockades have shown to be efficient in postoperative pain control, in the various orthopaedic procedures of the limbs. The aim of this study is to evaluate the existing data about the use of a continuous blockade of the lumbar plexus or femoral nerve, together with the indications for technique and therapy. METHODS: We considered the principal results of prospective, randomised studies described in literature about the assessment of a continuous peripheral blockade of the lumbar plexus or the femoral nerve in limb surgery. Furthermore we described the principal techniques for positioning the perinerval catheters in the considered sites, and the advised dosage regimen. RESULTS: The various studies report an adequate costs/benefits relation concerning the used techniques. The analysed studies not only report an adequate efficacy of the postoperative pain control, but often show an important benefit in terms of functional recovery of the operated limbs and on final outcome of the patient. CONCLUSIONS: The use of continuous blockades of the lumbar plexus or femoral nerve shows to be an important and effective instrument not only in terms of positive effects on postoperative pain control, but also in terms of relevant advantages concerning final outcome after surgery. Nevertheless these techniques should not be considered as the only approach to postoperative pain in the orthopaedic patient, but have to be included in a global, multidisciplinary and multimodal approach.
Humans↗
Continuous peripheral block in foot surgery.
Peripheral neural blockade techniques are commonly used procedures to provide perioperative anesthesia and analgesia. Several continuous infusion catheter techniques have been described to extend the use of peripheral neural blockade into the postoperative period as an effective method of providing pain management. The analgesic benefit of continuous local anesthetic peripheral block in the management of postoperative pain is primarily related to the properties of providing intense analgesia thereby reducing perioperative opioid requirements and opioid-related side effects and promoting early recovery of postoperative activity. Continuous peripheral nerve blockade seems to be effective in allowing major foot and ankle surgery to be done particularly on an outpatient basis with greater pain relief. The sciatic nerve is the largest nerve in the body and it lies deep in the posterior thigh. According to its anatomy, the sciatic nerve can then be reached at different levels from the parasacral space to the popliteal fossa, ideally identifying a sciatic line running from the inferior border of the gluteus maximus muscle between the greater throcanter and the ischiatic tuberosity to the popliteal fossa. A variety of continuous peripheral blocks have been described in this paper including continuous sciatic block at several levels (para-sacral nerve block, subgluteal sciatic nerve block) and popliteal nerve block.
Foot↗
[Two in one block for carotid surgery].
The choose of the best anaesthesia for carotid surgery is a very debated item: the locoregional techniques probably offer more hemodynamic stability and a direct neurologic monitoring, while general anaesthesia allows the complete control of airways and ventilation and reduces the global stress for the patient. This review analyzes the data of studies that compare general and locoregional anaesthesia. Among the latter, possibly elective techniques, the one described by Winnie combines an optimal analgesic efficacy with the lowest rate of adverse effects. A single bolus of a local anesthetic injected at a C4 level (apex of scalene muscles triangle) guarantees a complete block of the superficial and deep cervical plexuses.
Anesthesia, Local↗
Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients.
BACKGROUND: Fungal infections (FI) after solid organ transplantation (Tx) remain a major cause of morbidity and mortality. Aspergillus and Candida account for more than 80% of FI. METHODS: One thousand nine hundred and sixty-three patients undergoing thoracic organ Tx [1,852 heart and 111 lung (35 heart-lung Tx, 30 double-lung Tx, 46 single-lung Tx)] in 12 Italian Centers between November 1985 and January 1997 were included in the study. RESULTS: Fifty-one patients (41 heart Tx - 2.2%; 9 heart-lung Tx - 25.7%; 1 single-lung Tx - 2.2%) developed 53 invasive FI at a median of 58 days (range 6-2479) after Tx. Aspergillosis was the most frequent FI in our series accounting for 64.1% (34/53) of all FI [A fumigatus, n=29 (85.3%); A nidulans, n=2 (5.9%); A niger, n=2 (5.9%); A terreus, n=1 (2.9%)]; 30 (88.2%) patients developed invasive lung aspergillosis, 2 (5.9%) a tracheobronchitis, 1 (2.9%) a skin infection, and 1 (2.9%) a sternal wound infection. Twelve patients (22.6%) developed candidiasis [C albicans, n=8 (66.6%); C krusei, n=1 (8.3%); C glabrata, n=1 (8.3%); C parapsilosis, n=1 (8.3%); C sake, n=1 (8.3%)]. There were seven episodes (58.3%) of candidemia, two (16.7%) esophagitis, two (16.7%) gastritis, and one (8.3%) tracheobronchitis. Mortality was 29.4% for patients developing aspergillosis and 33.3% for those experiencing candidiasis. Furthermore, four patients developed the following: one C neoformans meningitis, one Sporothrix cyanescens pneumonia, one Rhizopus spp. tracheobronchitis, and one Trichosporon beigelii disseminated infection. Three additional patients were diagnosed affected by deep mould infection by histology alone. CONCLUSIONS: Deep-seated FI were relatively rare in our series, although their mortality rate is still very high.
Adult↗
High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders.
Epstein-Barr virus (EBV) DNA was quantitated in peripheral blood mononuclear cells (PBMC) from 25 healthy subjects, 105 asymptomatic solid-organ transplant (SOT) recipients, and 15 SOT recipients with symptomatic EBV infections by using a newly developed quantitative-PCR technique. Patients with symptomatic EBV infections had significantly higher (P < 0.001) median EBV DNA levels than asymptomatic SOT recipients and immunocompetent individuals. In SOT recipients, the positive predictive value of EBV DNA levels of >1, 000 genome equivalents (GE)/0.5 microg of total PBMC DNA was 64.7% for symptomatic EBV infection, while the negative predictive value was 96.1%. In 19 of 32 (59.3%) asymptomatic SOT recipients, EBV DNA levels were consistently below 1,000 GE for as long as 18 months, while 10 of 32 (31.2%) patients had 1,000 to 5,000 EBV GE at least once during follow-up. In a minority of patients (3 of 32; 9.3%), >/=5,000 GE could be detected at least once during follow-up. Reduction of immunosuppressive treatment decreased EBV DNA levels by >/=1 log(10) unit in patients with symptomatic EBV infections. Quantification of EBV DNA is valuable for the diagnosis and monitoring of symptomatic EBV infections in SOT recipients.
Adolescent↗
Vancomycin-resistant Enterococcus faecium infection in three children given allogeneic hematopoietic stem cell transplantation: clinical and microbiologic features.
BACKGROUND AND OBJECTIVES: The emergence of vancomycin-resistant enterococci (VRE) as nosocomial pathogens is a major problem in the US; in Europe, VRE nosocomial infections are uncommon and only rarely have been reported in Pediatric or Neonatal Units. The aim of this study is to report on the clinical and microbiological features of VRE infections in 3 children given hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Five episodes of vancomycin-resistant Enterococcus faecium (VREF) infection were diagnosed in 3 children given an allogeneic HSCT. Molecular methods, such as random amplification of polymorphic DNA (RAPD) fingerprinting and automated ribotyping, were used in order to define the circulation of strains. RESULTS: All the isolates were resistant to all commercially available agents and showed the VanA genotypic profile. All children were successfully treated with the combination of quinupristin/dalfopristin (QD) plus teicoplanin (TEC), although treatment was not sufficient to eradicate the micro-organism promptly from the gastrointestinal tract. All our children are still alive. After the first isolation of VRE, a surveillance protocol was started and we documented that the rate of colonization in children and their mothers was less than 1.5%. The RAPD method demonstrated the possible nosocomial transmission of one strain. INTERPRETATION AND CONCLUSIONS: Our experience demonstrates that VRE infection is a life-threatening complication in children given HSCT. Prompt diagnosis of this infection and its treatment with the combination of QD and TEC can successfully manage this severe infection in profoundly immunocompromised patients.
Anti-Bacterial Agents↗
Cytomegalovirus PP65 antigenemia monitoring as a guide for preemptive therapy: a cost effective strategy for prevention of cytomegalovirus disease in adult liver transplant recipients.
BACKGROUND: The aim of the study was to assess the incidence of cytomegalovirus (CMV) infection and disease in adult liver transplant recipients, using routine preemptive therapy guided by the pp65 antigenemia test. METHODS: Antigenemia was monitored weekly after liver transplantation (OLTX) for the first 3 months, and once a month for another 3 months. CMV seronegative recipients were treated preemptively for the first positive antigenemia. Seropositive recipients were treated only when their antigenemia count reached a threshold of > or =100 positive cells per 200,000 leukocytes. RESULTS: A total of 144 patients were included between June 1994 and April 1995, of which 137 (95%) were primary OLTX. The percentage of positive antigenemia and CMV disease was 55 and 8%, respectively. Seventy-eight (54%) patients were protocol-monitored for the entire follow-up (group 1) and received appropriate preemptive therapy, although 66 (46%) patients had protocol violation by having missed blood samples or blood drawn at unscheduled times (group 2). Using Cox's proportional hazards model, patients with a first antigenemia count of >11 leukocytes had a significantly higher rate of CMV disease compared to patients with an antigenemia count < or =11 leukocytes (RR = 7.3, 95% confidence interval = 2.2 to 24.5). In a multivariate Cox regression analysis, adjustments were made to control for: group 1 versus group 2, use of OKT3, and serology risk categories. This analysis showed that the relative rate of CMV disease was still significantly higher among patients with antigenemia count >11 leukocytes (adjusted RR = 4.9, 95% confidence interval = 1.3 to 18.1). The estimated cost of preemptive therapy was less than that of prophylaxis with i.v. (14-day course) or oral (90-day course) ganciclovir. CONCLUSIONS: Preemptive therapy guided by pp65 antigenemia is a useful and cost effective strategy for prevention of CMV disease.
Adult↗
Reconstruction of human immunodeficiency virus (HIV) sub-epidemics in Italian regions.
BACKGROUND: The spread of human immunodeficiency virus (HIV) infections is likely to consist of sub-epidemics in local areas and/or risk groups. Small-area risk group specific analyses may thus be a suitable means of better understanding and controlling the epidemic course. METHODS: An age, period, and cohort back-calculation method was used to reconstruct region-specific epidemics of HIV infection. The HIV infection incidence rates were estimated for individual Italian regions by using as denominator the specific risk category population (i.e. intravenous drug user population [IDU], homosexual/ bisexual population [MSWM], and Italian general population for heterosexual contacts [HST]). Incidence rates obtained in this way represent the risk of HIV infection conditional to belonging to the specific sub-group of the population. RESULTS: The HIV epidemic is heterogeneous in terms of gender, risk category and region. The highest risk of HIV infection has been estimated in the Lombardia region (North-West area) among men belonging to the IDU category in 1985. In recent years, a trend of decrease in HIV has been estimated, especially among IDU and MSWM. For the HST category, some regions have shown trends of great increase, particularly on the island of Sardegna and the regions of Puglia and Sicilia (Southern Italy). In 1987, most HIV infections were observed among IDU (39-90%), while in 1992 the MSWM and HST categories made the greatest contribution to the HIV epidemic. CONCLUSIONS: The results stress the idea of sub-epidemics rather than a single epidemic affecting the entire country. Some Southern regions emerge as areas in which the spread of HIV infections, although still at a rather low level, should cause considerable concern, particularly the trend of new infections by heterosexual transmission involving the general population. Detailed information on levels and trends of HIV infection epidemics at the local level are essential for surveillance purposes and for planning health care facilities, and can highlight areas in which preventive measures can be effective.
Disease Outbreaks↗
Ganciclovir resistance as a result of oral ganciclovir in a heart transplant recipient with multiple human cytomegalovirus strains in blood.
BACKGROUND: The emergence of a ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) strain in a heart transplant recipient (HTR) coinfected by multiple HCMV strains was investigated. METHODS: A HTR with primary HCMV infection was treated with three induction courses of intravenous GCV followed by a 2-month maintenance treatment with oral GCV. HCMV antigenemia, viremia, and leukoDNAemia levels were monitored. GCV susceptibility was analyzed by an immediate-early antigen plaque reduction assay and by a rapid screening assay performed using peripheral blood leukocytes (PBL) as viral inoculum. The viral population in blood was investigated by restriction analysis of multiple genome regions. UL97 and UL54 genes were sequenced in parallel in both HCMV isolates and the relevant PBL samples. A rapid molecular assay for detection and quantitation of the GCV-resistant mutant was developed. RESULTS: The emergence of a GCV-resistant UL97 mutant (Cys-607 --> Tyr) was responsible for treatment failure during oral GCV therapy. The genetic analysis of the HCMV population showed the sequential appearance in blood of two unrelated strains (referred to as A and B). Strain A most likely derived from the transplanted organ and strain B from a subsequent blood transfusion. The resistant variant (Br) emerged from strain B and became predominant "in vivo" under the GCV pressure. However, after foscarnet administration, the resistant mutant disappeared in viral isolates, whereas it was still present as a minor proportion in PBL samples. CONCLUSION: (a) Oral GCV may select resistant strains in transplanted patients; (b) results of the rapid screening assay were clinically useful for shifting to an alternative treatment, thus avoiding the appearance of HCMV disease; (c) virus isolation may not be the most reliable approach to detection of HCMV drug-resistant strains; (d) a novel molecular assay for rapid detection of UL97 Cys-607 --> Tyr mutation directly in clinical specimens was developed, allowing earlier "in vivo" detection of the resistant mutant.
Administration, Oral↗
Human cytomegalovirus (HCMV) leukodnaemia correlates more closely with clinical symptoms than antigenemia and viremia in heart and heart-lung transplant recipients with primary HCMV infection.
BACKGROUND: In the last few years, human cytomegalovirus (HCMV) viremia, pp65 antigenemia, and leuko- and plasma-DNAemia have been developed to quantitate virus in blood of immunocompromised patients with HCMV infection. However, thus far, no conclusive studies have been performed to define the correlation of each of the different assays with clinical symptoms in primary HCMV infections. METHODS: This correlation was investigated in a population of 20 heart and heart-lung transplant recipients with primary HCMV infection using standardized virological methods. RESULTS: Median peak HCMV viremia, antigenemia, and leukoDNAemia levels were 110 (0-2,000) p72-positive fibroblasts, 450 (27-2,000) pp65-positive leukocytes, and >10,000 (1,358-10,000) genome equivalents (GE) in the 14 symptomatic patients and 18 (1-130) p72-positive fibroblasts, 86.5 (5-350) pp65-positive leukocytes, and 248 (10-863) GE in the six asymptomatic patients, respectively. The difference was statistically significant for antigenemia (P=0.009) and leukoDNAemia (P<0.0001). However, on an individual basis, unlike viremia and antigenemia, all DNA peaks of the 6 asymptomatic patients were below the DNA range of the 14 symptomatic patients (<1,000 GE), while all the 14 symptomatic patients had DNA peaks higher than those of asymptomatic patients (>1,000 GE). Follow-up confirmed these results, showing that 1,000-2,000 GE was the threshold zone for emergence of clinical symptoms. Symptoms were never observed in patients with secondary DNA peaks, except for one patient suffering from an HCMV organ localization (HCMV gastritis). CONCLUSIONS: LeukoDNAemia is the viral parameter of choice for monitoring of primary HCMV infections and antiviral treatment in heart and heart-lung transplant recipients. In this patient population, antigenemia-guided preemptive therapy could be replaced by leukoDNAemia-based antiviral therapy.
Adolescent↗
Combined human cytomegalovirus and hepatitis C virus infections increase the risk of allograft vascular disease in heart transplant recipients.
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Adolescent↗
The impact of the 1993 European revision of the AIDS case definition on back-calculation estimates: an application in Italy.
OBJECTIVES: The revision of the case definition for AIDS within a given observation period causes discontinuity points on the epidemic curve to which back-calculation procedures can be sensitive. The aim of this work is to characterize the impact of the 1993 European revision of AIDS case definition and to evaluate the degree of distortion by which back-calculation estimates obtained on Italian data are affected. METHODS: The back-calculation procedure used, is a generalization of standard methods for estimating and projecting the AIDS epidemic. Age at onset of HIV infection, incubation time distribution, susceptible population and competitive non-AIDS mortality rates for infected persons are included in the estimation process. RESULTS: Back-calculation estimates resulted to be sensitive to the discontinuity point that the 1993 revision of AIDS case definition induced on the epidemic curve. The resulting effect is a tendency to overestimate HIV incidence in recent years by 20-40%. The maximum effect was found using data with end of AIDS cases at December 1993. The overestimation is a transient effect, that is, it is expected to almost disappear in 1995-1996. CONCLUSIONS: The introduction of the 1993 European revision of AIDS case definition caused distortion of back-calculation estimates in Italy, leading to overestimate incidence and prevalence of HIV infection for recent years. It is believed that this effect has occurred in all countries that adopted the 1993 European revision of AIDS case definition, and its characterization is potentially useful for further changes of AIDS case definition in the future.
Acquired Immunodeficiency Syndrome↗