IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience.

BACKGROUND: Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients. METHODS: 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed. RESULTS: IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDH mutational status: 61% in IDHmut vs. 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10-57) for IDHmut vs. 57% (95%CI: 30-77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1-65) IDHmut vs. 16% (95%CI: 0.7-52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt. CONCLUSIONS: This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed.

An Update on Heart Transplantation in Human Immunodeficiency Virus-Infected Patients.

Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.

Making patient centered care a reality: a survey of patient educational programs in Italian Cancer Research and Care Institutes.

BACKGROUND: Educational intervention represents an essential element of care for cancer patients; while several single institutions develop their own patient education (PE) programs on cancer, little information is available on the effective existence of PE programs at the level of research and care institutes. In Italy such institutes--Istituti di Ricovero e Cura a Carattere Scientifico--are appointed by the Ministry of Health, and 11 (Cancer Research & Care Istitute-CRCI) of the 48 are specific for cancer on the basis of specific requirements regarding cancer care, research and education. Therefore, they represent an ideal and homogeneous model through which to investigate PE policies and activities throughout the country. The objective of this study was to assess PE activities in Italian CRCI. METHODS: We carried out a survey on PE strategies and services through a questionnaire. Four key points were investigated: a) PE as a cancer care priority, b) activities that are routinely part of PE, c) real involvement of the patients, and d) involvement of healthcare workers in PE activities. RESULTS: Most CRCI (85%) completed the survey. All reported having ongoing PE activities, and 4 of the 11 considered PE an institutional activity. More than 90% of CRCI organize classes and prepare PE handouts, while other PE activities (e.g., Cancer Information Services, mutual support groups) are less frequently part of institutional PE programs. Patients are frequently involved in the organization and preparation of educational activities on the basis of their own needs. Various PE activities are carried out for caregivers in 8 (73%) out of 11 institutes. Finally, health care workers have an active role in the organization of PE programs, although nurses take part in these activities in only half of CRCI and pharmacists are seldom included. CONCLUSIONS: The information arising from our research constitutes a necessary framework to identify areas of development and to design new strategies and standards to disseminate the culture of PE. This may ultimately help and stimulate the establishment of institutional integrated PE programs, including policies and interventions that can benefit a significant proportion of cancer patients.

Combined liver-kidney transplantation in patients infected with human immunodeficiency virus.

Although human immunodeficiency virus (HIV) infection has been a major global health problem for almost 3 decades, with the introduction of highly active antiretroviral therapy in 1996 and effective prophylaxis and management of opportunistic infections, mortality from acquired immunodeficiency syndrome has decreased markedly. In developed countries, this condition is now being treated as a chronic condition. As a result, rates of morbidity and mortality from other medical conditions leading to end-stage liver, kidney, and heart disease are steadily increasing in individuals with HIV. Because the definitive treatment for end-stage organ failure is transplantation, the demand for it has increased among HIV-infected patients. For these reasons, many transplant centers have eliminated HIV infection as a contraindication to transplantation, as a result of better patient management and demand.

Differential dose adjustments of immunosuppressants after resuming boosted versus unboosted HIV-protease inhibitors postliver transplant.

Pharmacokinetic (PK) interactions between protease inhibitors (PI(s)) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LT(x)). The primary objective of this study was to evaluate the decreases in IS dosages necessary to maintain an appropriate therapeutic window (TW) after initiating PI-based antiretroviral therapy regimens post-LT(x). Single-center, PK cross-sectional study of consecutive HIV-infected adult patients who underwent LT(x) was done. Blood trough concentrations (C(t)) of IS were obtained using a commercial MEIA test; plasma C(t) of PI(s) were measured using HPLC. Twelve consecutive HIV-infected adult patients (11 males, 1 female) were enrolled. More rapid increases in IS plasma C(t) were observed 48 h after initiating ritonavir (RTV)-boosted PI therapy post-LT(x) than when using unboosted PI(s). Seven patients developed acute renal failure. The median fold decrease in IS dosages required to regain IS concentrations that were in the TW was 7.5 (range 6-14) after resuming boosted PI(s) and 2.9 (range 2-4) after unboosted PI(s). The overall median time necessary to reach IS TW after dose adjustment was 3.5 days (range 0-15). Unboosted PI(s) exhibited lesser PK interactions with IS than did RTV-boosted PI(s) and were thus more amenable to use in the post-LT(x) setting.

Efficacy and safety of atazanavir in patients with end-stage liver disease.

BACKGROUND: No data are available on the use of atazanavir (ATV) in patients with end-stage liver disease (ESLD), and guidelines discourage its use in this setting. The objective of our study was to evaluate the efficacy and safety of unboosted ATV in patients infected with HIV and suffering from ESLD who had been screened for orthotopic liver transplantation (OLT(x)). PATIENTS AND METHODS: This was a single-arm, 24-week pilot study. Atazanavir-naïve patients undergoing a highly active antiretroviral therapy were switched to ATV 400 mg daily plus two non-thymidine nucleoside reverse transcriptase inhibitors. RESULTS: Fifteen patients (ten males and five females, age range 36-59 years) were enrolled in the study. Of these, 11 (73%) had a baseline CD4 cell count > 200 microl(-1), and 12 had undetectable plasma HIV-RNA. 12 subjects (80%) were able to remain on ATV until week 24 (n = 10) or transplantation (n = 2). At the end of the study, the median CD4 cell count was 340 microl(-1) , and nine of the ten patients had undetectable RNA. During the study period, two patients received a transplant, two died of intracerebral hemorrhage and lactic acidosis, respectively, and one discontinued ATV. Among the ten patients completing the 24-week study, no significant changes from baseline were observed for most of the liver function markers, with the exception of unconjugated bilirubin (from 1.15 mg/dl to 1.32 mg/dl, p = 0.047). CONCLUSIONS: Unboosted ATV treatment did not worsen liver disease and was able to maintain or gain immunovirological eligibility for OLT(x) in all patients, with a limited effect on unconjugated bilirubin. These results suggest that ATV is an easy-to-use drug in patients with ESLD.

Incidence and clinical outcomes of ventilator-associated pneumonia in liver transplant and non-liver transplant surgical patients.

The aim of this study was to compare the incidence of ventilator-associated pneumonia (VAP) and clinical outcome among patients undergoing orthotopic liver transplantation (OLT) admitted to our surgical intensive care unit (ICU). Patients with an ICU stay longer than 4 days who had undergone surgery within 48 hours of admission were included in the study. Patients were subdivided into a liver transplant group (OLT) and no-liver transplant group (noLT). Diagnosis of VAP was based on microbiological data with a positive culture from a sample collected >or=48 hours after admission. VAP was defined as early if the positive culture occurred within the 4th day of admission, and late if after the 4th day. Three hundred seventy-three noLT and 71 OLT patients showed no differences in sex, mean severity score on admission (SAPS II), length of stay, and outcomes. The incidence of VAP was also similar in the 2 groups (27.3% in the noLT group vs 25.3% in the OLT group). Both in the OLT and noLT groups, the VAP patients showed higher (P< .05) SAPS II scores on admission, length of ICU stay, and mortality rates than the non-VAP patients, without any difference between the 2 groups. VAP is a frequent complication in ICU surgical patients, particularly those with high severity scores on admission. In an ICU surgical population, liver transplantation per se does not seem to increase the patients' risk either for VAP acquisition or for bad outcomes.

What is the biopsychosocial role of human immunodeficiency virus positivity in patients with end-stage liver disease who undergo orthotopic liver transplantation?

INTRODUCTION: Since 2003 the National Research Program for Solid Organ Transplantation in patients with human immunodeficiency virus (HIV) is active at our liver transplantation center. Patients with HIV who enter this protocol are assessed by the Consultation Liaison Psychiatry Service. The aim of the present study was to evaluate their psychiatric comorbidity. METHODS: An observational prospective study was conducted comparing end-stage liver disease (ESLD) patients with and without HIV. After the assessment, the psychiatrist compiled the Transplant Evaluation Rating Scale (TERS) and the Montgomery Asberg Depression Rating Scale (MADRS). Baseline evaluation was made before inclusion on the OLT waiting list and the follow-up evaluation was made 12 months later. RESULTS: From January 2003 to December 2006 we assessed 553 patients: 39 (6%) with HIV and 361 (94%) without HIV. The 2 groups were homogeneous for gender (75% of male patients; P=not significant [NS]) but not for age (46+/-5 vs 56+/-9; P=NS). Psychiatric history was negative in 176 (49%) patients without HIV and in 6 (15%) patients with HIV (P< .001). At baseline psychiatric comorbidity was present in 33 HIV patients (85%) and in 148 non-HIV patients (41%; P< .001). At follow-up MADRS highlighted an improvement in all of the items for HIV patients. In the non-HIV group, the variation was as follows: baseline, 7.10; follow-up, 8.15. In the HIV group, the variation was as follows: baseline, 10.20; follow-up, 4.09 (P< .001). The average score at TERS was higher among patients with HIV (43+/-9 vs 35+/-9; P=NS). CONCLUSIONS: At baseline HIV patients with ESLD showed a higher rate of psychopathology, but they improved at follow-up; the contrary happened in the non-HIV group.

Extra-axial chordoma: a clinicopathologic analysis of six cases.

Extra-axial chordoma is an exceedingly rare tumor, with only 28 cases reported in the literature to date. Axial and extra-axial chordoma exhibits complete morphologic and immunophenotypic (expression of brachyury) overlap. However, in consideration of the non-canonical presentation, extra-axial chordoma is under-recognized and often misdiagnosed, most often as extraskeletal myxoid chondrosarcoma or myoepithelioma. To increase our understanding of the clinicopathologic features of extra-axial chordoma, six cases have been retrieved from the files of the Istituto Ortopedico Rizzoli and of the General Hospital of Treviso. The clinicoradiologic, morphologic, and molecular features have been analyzed, and the follow-up was updated. Our series included four female and two male patients; their ages ranged from 20 to 67 years (mean 45.8 years). All patients presented with a single mass localized in four cases in the soft tissue (posterior arm, left leg, dorsal aspect of the foot, and popliteal fossa), and in two cases in the bone (radius and second metacarpal bone). Grossly, the neoplasm was lobulated, with a fleshy cut surface and a diameter ranging between 0.8 and 8 cm (mean 3.4 cm). Morphologically, all six cases showed an epithelioid cell proliferation organized in nests and cords demarcated by fibrous septa and set in an abundant extracellular myxoid matrix. Neoplastic cells featured hyperchromatic nuclei and abundant vacuolated cytoplasm. Immunohistochemically, all six cases were strongly positive for EMA, cytokeratin AE1/AE3, S100, and brachyury. INI1 nuclear expression was retained. Smooth muscle actin, calponin, p63, and GFAP were all negative. Fluorescent in situ hybridization (FISH) analysis did not reveal rearrangements involving NR4A3, FUS, and EWSR1 genes. At follow-up (mean 55 months), all patients were alive without disease after local surgical treatment. One patient underwent thigh amputation following multiple local recurrences and inguinal node metastases treated with marginal resection. In conclusion, primary extra-axial chordoma is an extremely rare neoplasm with distinct morphological and immunohistochemical features. Immunomorphology and molecular analysis allow distinction from both extraskeletal myxoid chondrosarcoma and myoepithelioma. Complete surgical resection appears to be curative.

Gram-positive bloodstream infections in liver transplant recipients: incidence, risk factors, and impact on survival.

The objective of the study was to assess the incidence, risk factors, and survival of gram-positive bloodstream infections (GP-BSI(s)) among liver transplant recipients during the first year after transplantation. Between October 2000 and September 2006, 42 episodes of GP-BSI(s) occurred in 205 patients with an overall incidence of 0.20 episodes/patient. Coagulase-negative staphylococci were detected in 45.2% of cases, Enterococcus species in 42.9% (E faecalis, eight; E faecium, seven; E avium, two; E gallinarum, one) and Staphylococcus aureus in 11.9%. Retransplantation was the only independent risk factor for GP-BSI (odds ratio [OR], 0.253; 95% confidence interval (CI), 0.089 to 0.715; P = .009). Thirty-day mortality rate was 28.5% and S aureus infections were related to a poorer outcome. It is noteworthy that all the isolates of S aureus were methicillin-resistant. Ampicillin was inactive against all the strains of E faecium and 50% of E avium isolates, but active against all E faecalis and E gallinarum strains. All the isolates were glycopeptide-susceptible. No significant differences in mortality rate were observed in relation to sex, etiologies of end-stage liver disease, cytomegalovirus infection/reinfection, type of donor, rejection, or retransplantation. GP-BSI, the only independent risk factor for death (OR, 0.262; 95% CI, 0.106 to 0.643; P = .003), reduced the survival rate by 26% in the first year posttransplant. In conclusion, GP-BSI(s) impact significantly on morbidity and mortality posttransplant, particularly among retransplantations. Control measures are required to reduce the incidence of GP-BSI(s) in liver transplant recipients. These findings must be considered when empirical antimicrobial therapy is indicated while awaiting blood-culture results.

Fatal cytomegalovirus necrotising enteritis in a small bowel transplantation adult recipient with low pp65 antigenaemia levels.

Although advances in immunosuppressive therapy have led to increased survival of solid organ transplantation recipients, it is well established that current protocols have been associated with an increased risk of developing tissue-invasive infections. In particular, cytomegalovirus still represents an important cause of morbidity. We report a case of cytomegalovirus infection involving the graft ileum with documented necrotising enteritis that developed after small bowel transplantation. The patient, a 56-year-old Caucasian female with a postsurgery short bowel syndrome, underwent a small bowel transplantation. Immunosuppression was maintained by combination of tacrolimus, steroids and daclizumab. Both the donor and the recipient were serologically negative for cytomegalovirus IgG. Nevertheless, ganciclovir prophylaxis was given for 21 days after surgery, as standard procedure. On hospital day 174, routine pp65 antigenaemia resulted positive (14/200,000 peripheral blood leukocytes). The patient was asymptomatic and preemptive ganciclovir therapy was instituted. In the following 3 days, due to a cytomegalovirus antigenaemia increase, ganciclovir was changed to foscarnet with subsequent virological response (7/200,000 peripheral blood leukocytes, on day 181). Two days later, the patient complained of acute abdominal pain and she underwent surgery for the diagnosis. Since the intraoperative findings consisted of a diffuse acute purulent peritonitis, the intestinal graft, together with native rectum, was removed. Biopsy specimens showed evidence of tissue-invasive cytomegalovirus infection. Postsurgery, the patient developed septic shock and died on day 198 as a consequence of multiple organ failure.

Posttransplant Mycobacterium tuberculosis disease following liver transplantation and the need for cautious evaluation of Quantiferon TB GOLD results in the transplant setting: a case report.

This report describes a case of pulmonary tuberculosis in a liver transplant patient without a history of previous exposure to Mycobacterium tuberculosis (MTB) complex. Prior to transplantation, the tuberculin skin test was negative and the QuantiFERON-TB Gold (QFT Gold), an interferon gamma-based blood test, was negative before and after transplant including a period beginning on postoperative day 55 when the patient developed a febrile illness with an interstitial infiltrate and pleural effusion that was unresponsive to broad-spectrum antibiotic therapy. Empiric treatment with isoniazid, ethambutol, and levofloxacin resulted in resolution of the clinical symptoms. A sputum culture grew MTB on postoperative day 87. This case illustrates the need for caution when QFT Gold is used as diagnostic tool for latent tuberculosis during the pretransplant assessment. Further studies evaluating the usefulness of QFT Gold and other interferon gamma tests in posttransplantation active infection are warranted.

Pharmacokinetic interaction between Amprenavir/Ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation.

The pharmacokinetic interaction between highly active antiretroviral therapy (HAART) and immunosuppressive drugs is a critical element in the management of patients with human immunodeficiency virus infection who undergo orthotopic liver transplantation (OLT). We describe the effect of the coadministration of Amprenavir/Ritonavir (APV/r) and FosAmprenavir (FosAPV) on cyclosporine (CsA) concentrations in two patients receiving OLT for end-stage liver disease due to hepatitis C Virus. Patient 1, who was maintained on 300 mg CsA twice a day with a trough concentration (C(trough)) around 250 ng/mL, restarted HAART 12 days after transplantation with 300 mg APV/r twice a day with corresponding APV C(trough) of 5293 ng/mL and RTV C(trough) of 186 ng/mL. Forty-eight hours after initiation of HAART, C(trough) of CsA was 1200 mg/mL, so it was necessary to reduce the CsA dosage 12-fold (50 mg every day) to achieve a therapeutic effect. In Patient 2, who was maintained on 300 mg CsA twice a day and a corresponding C(trough) of 400 ng/mL, HAART was restarted 12 days post-OLT with FosAPV 1400 mg twice a day. After 48 hours C(trough) of CsA was around 600 ng/mL and C(trough) of FosAPV, 1221 ng/mL. In this case it was necessary to reduce the CsA administration 3.5-fold (175 mg every day). In conclusion, therapeutic drug monitoring was necessary to monitor HAART and CsA post-OLT to prevent toxicity due to both therapies. The use of FosAPV without ritonavir boostering is sufficient to maintain adequate CsA blood concentrations, avoiding any event of toxicity.

Dental features in patients with Turner syndrome.

AIM: This was to investigate the dental characteristics (caries sensitivity and tooth crown size of permanent elements) in subjects affected by Turner Syndrome (TS). PATIENTS AND METHODS: A group of 25 patients affected by TS, aged from 4 to 18 years, was selected and the data were compared to those of an age matched control healthy group. The caries index values in TS patients are higher in the permanent (6.4 vs. 3.9), mixed (0.5 vs. 0.75) and primary dentition (0 vs. 1). The mesio-distal diameter in TS patients was significantly reduced for every tooth measured (in particular for the lower first permanent molar). RESULTS AND CONCLUSION: This investigation confirms that numeric aberration of the X chromosome most likely affects the quantitative and qualitative excretion of amelogenin so that teeth often present enamel defects (reduced crown size and enamel hypoplasia). High caries index values (DMFT) highlight the demand of early preventive measures mostly focused on special care patients.

Role of therapeutic drug monitoring in a patient with human immunodeficiency virus infection and end-stage liver disease undergoing orthotopic liver transplantation.

Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4(+) count (>500 cells/mm(3)) and HIV-1 RNA (<50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new anti-retroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.

Rituximab as treatment of posttransplant lymphoproliferative disorder in patients who underwent small bowel/multivisceral transplantation: report of three cases.

This report describes three cases of posttransplant lymphoproliferative disorder (PTLD) in multivisceral/small bowel transplant patients treated with rituximab (anti-CD20 monoclonal antibodies). In two cases (one of which was a B-cell lymphoma) a good response to therapy was achieved. A third case (with polymorphic PTLD with low CD20 expression) developed a refractory rejection and PTLD was still documented on graftectomy. Rituximab was well tolerated, and a reduction of Epstein-Barr virus (EBV) viral load was documented by quantitive competitive-EBV polymerase chain reaction. Efficacy of therapy needs to be assessed in controlled studies.

Caries and adolescents.

AIM: The rapid improvement in oral health conditions in childhood and adolescence and the ceaseless bombardment of information from the mass media have, during little more than 30 years, brought about a decrease in the prevalence of caries of more than 70% in most European Union countries. The study aimed to take an accurate picture of oral health conditions and dental prevention habits among adolescents. METHODS: The research was conducted on a group of 340 adolescents (12-16 years) in the province of Bologna (Imola) and used the SPSS to compare clinical and epidemiological parameters with medical-history data traditionally understood to be determinant for caries. RESULTS: From an analysis of the data it emerged that the mean value of the decay, missing or filled tooth (DMFT) index in the group was 1.8765 +/- 2.1987 and that the plaque index (according to Löe and Silness) was 1.2519 +/- 0.4213. CONCLUSIONS: Crossing the data obtained, a highly significant correlation emerged (P=0.004) between plaque and caries indexes, and confirmed the primary role of bacterial plaque in causing caries. Unlike what we expected and unlike data reported in the international literature, the caries index was not found to be correlated in a statistically significant way with frequency of brushing, ''preferential consumption of sweet snacks'' (P=0.231) nor ''eating sweets and chewing gum'' (P=0.159) or with taking fluoride tablets (P=0.406). The key to success during adolescence is rooted in childhood; it is the pediatricians' and parents' job to guide and control the acquisition of correct dietary and oral hygiene habits.

Case report: Alagille syndrome.

The clinical case of a boy aged 6 years suffering from Alagille syndrome is described. This is a rare genetic disease characterised, from the hepatic point of view, by anomalies of the intrahepatic biliary ducts (in terms of number, histology and immunohistochemistry) with cholestasis; from the systemic point of view it is characterised by anomalies of various systems (heart, musculoskeletal system, eyes, face, kidneys and nervous system). The patient was referred for dental consultation by the Pediatric Cardiology Section, Sant'Orsola-Malpighi Polyclinic, Bologna City Hospital. Medical history indicated liver transplantation at 3 years; immunosuppressive treatment; heart disease with low risk of bacterial endocarditis (interventricular defect and systolic murmur). Objective examination revealed a dental formula compatible with his age, of a decided green colour (above all the permanent dentition) with numerous caries lesions on the posterior deciduous teeth. In agreeing the treatment plan with the cardiologist (treatment of caries and sealing the fissures and cracks in the permanent first molars) it was decided that antibiotic prophylaxis was not required since such conservative treatment is not at risk for bacterial endocarditis. The patient returned 15 min after the end of the second session with marked swelling of the right upper hemi-lip. Having excluded traumatic origin, a hypothesis was formulated of hypersensitivity to products used during the dental session, in particular talcum-coated gloves and latex rubber dam. The patient was referred immediately to the Dermatology Service, Sant'Orsola-Malpighi Polyclinic, for the appropriate dermatological tests (prick test and epicutaneous test) which confirmed the suspected diagnosis: urticaria from contact with latex materials. The clinical case described confirms the need for the dentist of an interdisciplinary approach in patients suffering from systemic diseases and/or syndromes.

Sclerosing epithelioid fibrosarcoma of the thigh: report of two cases with synchronous bone metastases.

We report two cases of sclerosing epithelioid fibrosarcoma occurring in the deep soft tissue of the thigh, confirmed by molecular analysis and associated with bone metastases in the lumbar vertebrae and the iliac wing at the time of diagnosis. Synchronous bone metastases of sclerosing epithelioid fibrosarcoma are extremely difficult to diagnose because clinical and radiological features are not specific. In addition, the range of differential diagnoses is very wide, including metastatic carcinoma and osteosarcoma. At present, all but three published cases of sclerosing epithelioid fibrosarcoma with bone metastases showed bone metastases during follow-up. We confirm in our two cases that the distinct pattern of immunohistochemical staining for MUC4, associated with the absence of staining for both SATB2, a marker of osteoblastic differentiation, and pan-cytokeratin, allows differentiating between sclerosing epithelioid fibrosarcoma and metastatic carcinoma or osteosarcoma.

A long-term prospective evaluation of first-degree relatives of panic patients who underwent the 35% CO2 challenge.

BACKGROUND: This follow-up study investigated the potential priming effect of the 35% CO2 challenge on the development of anxiety disorders and/or panic attacks in healthy first-degree relatives of panic patients across a period of 3-4 years subsequent to the challenge. METHODS: Thirty-one relatives who underwent the 35% CO2 challenge 3-4 years before and 14 relatives, free from psychiatric diagnoses in the same period, were directly reevaluated for the presence of anxiety disorders and panic attacks. RESULTS: None developed anxiety disorders and only 1, among relatives previously tested with the 35% CO2 challenge, reported sporadic panic attacks. CONCLUSIONS: The 35% CO2 challenge is a safe research paradigm in the investigation of healthy subjects with a familial vulnerability to panic, and CO2 hypersensitivity might be considered a trait marker of an underlying familial vulnerability to panic disorder.