[Pneumocystis jirovecii pneumonia-an opportunistic infection undergoing change]. / Pneumocystis-jirovecii-Pneumonie ­ eine opportunistische Infektion im Wandel.

Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other immunocompromised patients, e.g. after organ or allogeneic stem cell/bone marrow transplantation, patients with hematologic malignancies or autoimmune diseases. The diagnosis of PcP relies on a critical evaluation of clinical symptoms, risk factors, radiologic features and microbiological tests. High dose cotrimoxazole is the most effective therapeutic option. Rapid initiation is essential, since mortality is especially high in patients admitted to intensive care with respiratory failure. This article reviews the current epidemiology of PcP and highlights the diagnostic and therapeutic options. Recommendations for primary and secondary prophylaxis are summarized.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4).

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: The risk and spectrum of infections in patients receiving CD22-targeted agents (i.e. inotuzumab ozogamicin) are similar to those observed with anti-CD20 antibodies. Anti-Pneumocystis prophylaxis and monitoring for cytomegalovirus (CMV) infection is recommended for patients receiving CD30-targeted agents (brentuximab vedotin). Due to the scarcity of data, the risk posed by CD33-targeted agents (gemtuzumab ozogamicin) cannot be assessed. Patients receiving CD38-targeted agents (i.e. daratumumab) face an increased risk of varicella-zoster virus (VZV) infection. Therapy with CD40-targeted agents (lucatumumab or dacetuzumab) is associated with opportunistic infections similar to those observed in hyper-IgM syndrome, and prevention strategies (including anti-Pneumocystis prophylaxis and pre-emptive therapy for CMV infection) are warranted. SLAMF-7 (CD319)-targeted agents (elotuzumab) induce lymphopenia and increase the risk of infection (particularly due to VZV). The impact of CCR4-targeted agents (mogamulizumab) on infection susceptibility is difficult to distinguish from the effect of underlying diseases and concomitant therapies. However, anti-Pneumocystis and anti-herpesvirus prophylaxis and screening for chronic hepatitis B virus (HBV) infection are recommended. IMPLICATIONS: Specific management strategies should be put in place to reduce the risk and/or the severity of infectious complications associated to the reviewed agents.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid cells surface antigens [I]: CD19, CD20 and CD52).

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD19, CD20 and CD52 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: Although CD19-targeted agents (blinatumomab or inebilizumab) are not associated with an increased risk of infection, they may cause IgG hypogammaglobulinaemia and neutropenia. The requirement for prolonged intravenous infusion of blinatumomab may increase the risk of catheter-associated bloodstream infections. Infection remains the most common non-haematological adverse effect of anti-CD20 monoclonal antibodies, including severe respiratory tract infection, hepatitis B virus (HBV) reactivation and varicella-zoster virus infection. Screening for chronic or resolved HBV infection is recommended for patients receiving anti-CD20 monoclonal antibodies. Antiviral prophylaxis should be offered for 12-18 months to hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/anti-hepatitis B core antibody (HBc)-positive patients. Anti-Pneumocystis prophylaxis should be considered in patients receiving concomitant chemotherapy, particularly steroids. Alemtuzumab (anti-CD52) increases the risk of infections, in particular among leukaemia and solid organ transplant patients. These populations benefit from anti-Pneumocystis prophylaxis, prevention strategies for cytomegalovirus infection, and screening for HBV, hepatitis C virus and tuberculosis. Antiviral prophylaxis for at least 6-12 months should be provided for HBsAg-positive patients. IMPLICATIONS: As there are limited clinical data for many of the reviewed agents, special attention must be given to promptly detect and report emerging infectious complications.

[Fever of unknown origin]. / Fieber ungeklärter Ursache.

Fever of unknown origin (FUO) is defined as sustained unexplained fever despite intensive diagnostic evaluation and represents a particular diagnostic challenge. It can be classified into different categories, e.g. classical, nosocomial, neutropenic and HIV-associated FUO, which is based on the patient-specific clinical and immunological situation. Infections, malignant diseases and non-infectious inflammatory diseases have to be considered as the most important causes of FUO; however, no definitive diagnosis can be established in a substantial number of FUO patients despite an extensive diagnostic work-up. The present review focuses on the important diagnostic aspects as well as therapeutic options in FUO patients.

Are histopathological findings of diagnostic value in native valve endocarditis?

BACKGROUND: Optimal management of infective endocarditis (IE) depends on the early detection of IE-causing pathogens and on appropriate antimicrobial and surgical therapy. The current guidelines of the European Society of Cardiology (ESC) recommend histopathological examination as the gold standard for diagnosing IE Habib et al. (Eur Heart J 30:2369-2413, 2005). We hypothesize that histopathological findings do not provide additional information relevant to clinical decision-making. METHODS: We retrospectively reviewed a cohort of patients who had undergone surgery for native valve endocarditis (NVE) at the University Hospital Regensburg between September 1994 and February 2005. All episodes of intraoperatively confirmed endocarditis during this period were included in the study. Data were retrieved from surgical records, microbiological and histopathological reports, and medical files of the treating as well as admitting hospital. Pathogens were correlated with the site of manifestation of the affected heart valve and with clinical and histopathological findings. RESULTS: A total of 163 episodes of NVE were recorded and entered into our study for analysis. The valves affected were the aortic valve (45 %), the mitral valve (28 %), the aortic and mitral valve (22 %), and other valves (5 %). IE-causing pathogens were Staphylococcus aureus (22 %), viridans streptococci (18 %), enterococci (10 %), streptococci other than Streptococcus viridans (9 %), coagulase-negative staphylococci (5 %), miscellaneous pathogens (4 %), and culture-negative endocarditis (33 %). Infection with S. aureus was associated with high rates of sepsis, septic foci, and embolic events, while patients with enterococcal IE showed the highest rate of abscesses. Mortality rate in all subgroups was low without significant differences. However, histopathological findings correlated poorly with the pathogen involved and showed only few significant associations that were without clinical relevance. CONCLUSIONS: The clinical presentation of IE depends on the pathogen involved. Among the episodes of NVE examined, the histopathological examination of resected heart valves did not show any pathogen-specific morphological patterns and therefore did not provide any additional information of clinical value. Based on our findings, we recommend complementary cultures of the resected materials (valve tissue, thrombotic material, pacer wire) and implementation of molecular diagnostic methods (e.g., broad-range PCR amplification techniques) instead of histopathological analyses of resected valve tissue.

Infectious diseases publications in leading medical journals--a comparative analysis.

The representation of medical disciplines in leading journals may provide valuable information on their respective importance for both researchers and funding agencies. We were interested in the scientific contribution of infectious diseases to leading medical journals and their ranking compared to other medical disciplines. Original articles and short communications in three leading medical journals from 2003 to 2009 were analyzed by contributing medical discipline and by nation: The New England Journal of Medicine (NEJM), The Lancet, and the Journal of the American Medical Association (JAMA). The medical disciplines were selected according to a standard textbook (Harrison's Principles of Internal Medicine). Each article was categorized into one to three medical disciplines. The most frequently represented disciplines in 3,953 articles were cardiology (19.5 %), infectious diseases (18.6 %), and hematology/oncology (15.9 %). Each of the journals had another leading discipline: cardiology in JAMA, hematology/oncology in NEJM, and infectious diseases in The Lancet. In the American journals, contributions from US researchers dominated the field (52.6 % in NEJM, 73.6 % in JAMA), while the majority of papers in The Lancet originated from non-US residents (76.5 %). This study underlines the importance of infectious diseases as a medical discipline in clinical research.

Vaccination against pandemic H1N1 (2009) in patients after allogeneic hematopoietic stem cell transplantation: a retrospective analysis.

PURPOSE: Limited data are available on immunologic responses to primary pandemic H1N1 (2009) vaccination in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) recipients. In 2009 serologic responses to either pandemic H1N1 (2009) vaccine (n = 36) or pandemic H1N1 (2009) infection (n = 2) were studied in 38 HSCT recipients. METHODS: Responses were measured with a standard hemagglutination-inhibition assay. Fourteen patients had active chronic graft-versus-host disease (cGvHD) at the time of vaccination/infection and seven patients had cGvHD in remission; 11 patients had no immunosuppressive therapy, and 27 patients were on immunosuppressive therapy. Nineteen patients (53%) responded to pandemic H1N1 (2009) vaccination. Two patients had pandemic H1N1 (2009) infection without prior vaccination, and one patient had severe pandemic H1N1 (2009) infection with acute respiratory distress syndrome despite prior single vaccination. RESULTS: Non-responders to pandemic H1N1 (2009) vaccination more often had cGvHD (65 vs. 53%) and received second- or third-line therapy (53 vs. 11%), while responders mostly had first-line therapy for cGvHD. While vaccine responders had no or single agent immunosuppressive therapy, non-responders frequently received moderate or intense immunosuppressive therapy. All vaccine recipients previously treated with rituximab were non-responders. CONCLUSIONS: In summary, the overall response to pandemic H1N1 (2009) vaccination in HSCT recipients was modest. Patients receiving combined immunosuppressive therapy for steroid-refractory cGvHD barely responded to pandemic H1N1 (2009) vaccination.

Evaluation of the microcirculation of hepatocellular carcinomas using contrast-enhanced ultrasound with intraarterial and intravenous contrast application during transarterial chemoembolization with drug-eluting beads (DEB-TACE): preliminary data.

PURPOSE: The objective was the evaluation of microcirculation in hepatocellular carcinomas (HCC) in vivo by dynamic contrast-enhanced ultrasound (CEUS) after intravenous (i.v.) and intraarterial (i.a.) application of contrast agent during transarterial chemoembolization (TACE) using drug-eluting beads (DEB). PATIENTS AND METHODS: Eleven patients with HCC underwent CEUS directly before and immediately after DEB-TACE. The sonographic contrast agent was injected through the microcatheter intraarterially and intravenously. The grade of hypervascularization was evaluated before Bead application. The percentage of devascularization after Bead application was calculated and quantitative devascularization was carried out using time intensity curves (TIC). These results were compared to postinterventional angiography after Bead application and postprocedural computed tomography. RESULTS: The hypervascularization of HCC was marginal improved after i.a. contrast application compared to i.v. application (p = 0.163). The reduction of vascularization after Bead application correlated significant between i.a. and i.v. contrast application (p = 0.007) and decreased significant using TIC analysis (p = 0.003). Postinterventional angiography related with CEUS after i.a. sonographic contrast agent application. Extrahepatic tumor-feeding arteries were detected by a mismatch between i.a. and i.v. CEUS in one case. CONCLUSION: Quantification of the reduction of microvascularization using TIC analysis may be a valuable periinterventional tool during DEB-TACE. Intraprocedural CEUS with i.a. and i.v. ultrasound contrast agent injection may help finding extrahepatic tumor-feeding arteries.

[A 42-year-old farmer with nonspecific leucocytosis and elevated transaminases. Acute septic reaction in Coxiella burnetii infection]. / 42-jähriger Landwirt mit unklarer Leukozytose und erhöhten Transaminasen. Akute septische Reaction bei Coxiella-burnetii Infektion.

We report about a 42-year-old farmer with leucocytosis, elevation of transaminases and liver cirrhosis as an underlying condition. The diagnosis of Q fever hepatitis was made through liver biopsy and serology. Under therapy with doxycycline, transaminases initially increased again; after switching to ciprofloxacin, the patient could be discharged 3 weeks after admission. Q fever is caused by Coxiella burnetii. The most frequent acute manifestation is a self-limiting flu-like illness. Chronic Q fever mostly presents as endocarditis. The diagnosis is made through histology ("doughnut" granulomas), PCR, serology (acute: anti-phase II antibodies, chronic: anti-phase I antibodies) and culture. Standard therapy is doxycycline.

Percutaneous necrosectomy in patients with acute, necrotizing pancreatitis.

The objective of this retrospective study was to evaluate the outcome of patients with acute necrotizing pancreatitis treated by active percutaneous necrosectomy. By searching the radiological, surgical and internal medicine databases, all patients with acute necrotizing pancreatitis treated by active percutaneous necrosectomy between 1992 and 2004 were identified. Demographic, laboratory, and clinical data, and details about invasive procedures were collected by reviewing patient charts, radiological and surgical reports. The computed tomography severity index (CTSI) scores were determined by reviewing CT images. Eighteen patients were identified. Median Ranson score on admission was 2. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was median 22. Median CTSI score was 7. Initially all patients were treated with CT-guided drainage placement. Because passive drainage proved not to be effective, subsequent minimally invasive, percutaneous necrosectomy was performed. Eight out of 18 patients recovered fully without the need for surgery. Ten of 18 patients required additional surgical necrosectomy. For one of ten patients, percutaneous necrosectomy allowed postponing surgery by 39 days. Four of ten surgically treated patients died: three from septic multiorgan failure, one from pulmonary embolism. Percutaneous minimally invasive necrosectomy can be regarded as a safe and effective complementary treatment modality in patients with necrotizing pancreatitis. It is suitable for a subset of patients to avoid or delay surgery.

Outcome of patients with acute, necrotizing pancreatitis requiring drainage-does drainage size matter?

AIM: To assess the outcome of patients with acute necrotizing pancreatitis treated by percutaneous drainage with special focus on the influence of drainage size and number. METHODS: We performed a retrospective analysis of 80 patients with acute pancreatitis requiring percutaneous drainage therapy for infected necroses. Endpoints were mortality and length of hospital stay. The influence of drainage characteristics such as the median drainage size, the largest drainage size per patient and the total drainage plane per patient on patient outcome was evaluated. RESULTS: Total hospital survival was 66%. Thirty-four patients out of all 80 patients (43%) survived acute necrotizing pancreatitis with percutaneous drainage therapy only. Eighteen patients out of all 80 patients needed additional percutaneous necrosectomy (23%). Ten out of these patients required surgical necrosectomy in addition, 6 patients received open necrosectomy without prior percutaneous necrosectomy. Elective surgery was performed in 3 patients receiving cholecystectomy and one patient receiving resection of the parathyroid gland. The number of drainages ranged from one to fourteen per patient. The drainage diameter ranged from 8 French catheters to 24 French catheters. The median drainage size as well as the largest drainage size used per patient and the total drainage area used per patient did not show statistically significant influence on mortality. CONCLUSION: Percutaneous drainage therapy is an effective tool for treatment of necrotizing pancreatitis. Large bore drainages did not prove to be more effective in controlling the septic focus.

Outcome of hemato-oncologic patients with and without stem cell transplantation in a medical ICU.

OBJECTIVE: To assess the outcome of a mixed population of critical ill patients with haematological malignancies with special focus on the comparison of patients who underwent stem cell transplantation with non-transplanted patients. METHODS: Retrospective, unicentric analysis of 94 critical ill cancer patients in a tertiary care centre in a period of two years time. RESULTS: We analysed different variables at admission as well as different treatment modalities during the ICU stay. We compared the outcome by using chi-square test by Pearson for categorical variables and Kaplan-Meier as well as Cox-Regression for survival analysis. The general patients characteristics did not significantly differ between transplanted and non-transplanted patients. The overall ICU and hospital mortality were 43% and 54%. Considering just patients with mechanical ventilation we found ICU and hospital mortalities of 65% and 82% in the stem cell transplantation group vs. 67% and 74% in the non-transplanted group, respectively. As risk factors for overall mortality in multivariate analysis only the Simplified Acute Physiology Scale II and the need of ventilation remained significant. Between the underlying diseases mortality did not show significant differences at all. CONCLUSIONS: The outcome and prognosis of critical ill cancer patients has generally slightly improved over the last years. Our data show no statistically significant differences regarding outcome and prognosis between stem cell transplanted and non-transplanted patients receiving ICU treatment. A stem cell transplantation should not be considered a strong contraindication for ICU treatment or artificial ventilation.

Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs and CTRPs.

Adipose tissue has long been regarded as a mostly resting tissue that is dedicated solely to energy storage and release. However, in recent years, this view has changed dramatically following new insights into the metabolic and immunological functions of preadipocytes and adipocytes. There are several lines of evidence for the involvement of adipose tissue in innate and acquired immune responses. First, adipocytes are potent producers of proinflammatory cytokines, such as interleukin-6 and tumor necrosis factor (TNF), and chemokines. Furthermore, adipocytes secrete high amounts of adipokines, such as leptin, adiponectin and resistin, that regulate monocyte/macrophage function, and also secrete molecules associated with the innate immune system, such as the C1qTNF-related protein superfamily. Finally, preadipocytes and adipocytes express a broad spectrum of functional Toll-like receptors and the former can convert into macrophage-like cells. Collectively, these data clearly establish the role of adipose tissue as a new member of the immune system.

Cytokine and nitric oxide responses of monocyte-derived human macrophages to microsporidian spores.

Microsporidia are obligate intracellular parasites that emerged as opportunistic pathogens since the onset of the AIDS pandemic. They are capable of disseminating through the body using macrophages as vehicles. We incubated human macrophages with spores of all three Encephalitozoon spp. as well as with Vittaforma corneae, and the number of intracellular spores per cell was determined by fluorescence microscopy. Cell culture supernatants were collected and the content of TNF-alpha, INF-gamma, IL-10, and of nitric oxide was determined. Microsporidian spores did not induce a nitric oxide response in macrophages and there was a negative correlation between the number of intracellular spores and the amount of nitric oxide. TNF-alpha, INF-gamma, and IL-10 increased after simulation of macrophages with microsporidian spores but for TNF-alpha and INF-gamma no clear correlation of cytokine levels with the number of intracellular spores could be observed. A modulation of the nitric oxide response by intracellular microsporidia may contribute to the survival of microsporidia within the macrophage by a mechanism yet unknown.

[IKOP-Infection control in the operating theatreConsensus on the theme "Barrier measures during operations and invasive procedures"]. / IKOP-Infektionskontrolle im OperationsbereichKonsensus-Papier zum Schwerpunkt "Barrieremassnahmen bei Operationen und invasiven Eingriffen"

Postoperative surgical site infections remain frequent despite intensive control programs. With rising numbers of operations and invasive procedures in the outpatient setting and in immunocompromised patients, the prevention of wound infections presents a rapidly growing challenge to the medical community. Barrier measures including drapes and surgical gowns to prevent wound contamination, have clearly reduced the rate of wound infections. The optimal material characteristics for operating gowns and drapes are well defined, but there is still a long running controversy on the use of single-use versus reusable materials. We review the efficacy and ecological impacts of these different approaches. Currently no superiority of any of these approaches with regard to either efficacy or ecological impact can be found. The European Union has recently published a series of mandatory standards to specify material characteristics of barrier materials used in operating theatres (EN 13795). Their scope include production standards of these materials as well as specific processes in auditing their characteristics. The implementation of these norms will clearly present a challenge to European hospitals but will lead to better material characteristics in the end.

Long-term outcome and quality of care of patients with Staphylococcus aureus bacteremia.

To assess the long-term outcome and influence of clinical management of patients with Staphylococcus aureus bacteremia (SAB), 229 patients with blood cultures positive for Staphylococcus aureus between January 1997 and December 2000 were retrospectively identified and followed up. Risk factors, source of infection, treatment, clinical course, and outcome were recorded by chart review. For the assessment of 1-year survival, a questionnaire was sent to family doctors and government registration offices. Time of initial antibiotic therapy, duration of antibiotic treatment and performance of echocardiography were regarded as indicators of the quality of the clinical management of SAB. Among the 229 patients studied, 218 were evaluable for 1-year survival. Crude mortality after 1 year was 37.6% year. Within 30 days 43 (19.7%) patients had died, and 39 (17.9%) additional patients died thereafter. Using multivariate analysis, the following variables were associated with death: malignant disease (odds ratio [OR] 4.8; 95% confidence interval [CI], 2.6-8.9), pneumonia (OR, 3.6; 95%CI, 1.2-10.2), age >60 years (OR, 2.6; 95%CI, 1.5-4.5), and known source of infection (OR, 2.3; 95%CI, 1.3-4.1). Among 160 patients with a completely assessable treatment course 73 (46%) had received antibiotics for at least 14 days. A delay of antibiotic treatment of 1 day or more after microbiological diagnosis was observed in 28.3% of patients (i.e., 60 of 212 patients who received at least 1 dose of antibiotics). Echocardiography was performed in 101 (44.1%) cases. Overall, the findings indicate that standard guidelines for the management of SAB are followed only in part in clinical practice. In order to reduce the considerable mortality associated with SAB and to improve short- and long-term outcome, efforts should be made to increase adherence to recommendations.

Unusual and severe symptomatic impairment of neutrophil function after one cycle of temozolomide in patients with malignant glioma.

Temozolomide, a recently approved cytotoxic agent for the treatment of malignant glioma, has shown promising results in the treatment studies published so far. However, cytopenia and related infectious complications have been reported in 2-8% of cases. Here we present three treatment-naive patients with malignant glioma experiencing cytopenia and/or infectious complications after the first cycle of temozolomide. Neutrophils obtained from each patient up to 6 weeks after the end of the temozolomide application showed normal phagocytic capacity but decreased oxygen radical production and thus impairment of microcidal activity. Our data suggest that a prolonged impairment of the immunological defense may occur in temozolomide-treated patients.

BEACOPP therapeutic regimen for patients with Hodgkin's disease and HIV infection.

BACKGROUND: Hodgkin's disease (HD) is the most common non-AIDS-defining tumor diagnosed in HIV-infected patients. Antineoplastic treatment is difficult considering the underlying immunodeficiency caused by HIV itself and may increase the risk of opportunistic infections. The purpose of this study was to evaluate the efficacy and safety of the chemotherapeutic regimen bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) in HIV-infected patients with HD (HIV-HD). PATIENTS AND METHODS: Twelve patients with HIV-HD were scheduled to receive six cycles of BEACOPP. Five patients received concomitant antiretroviral therapy. Two patients received additional radiotherapy. Restaging was carried out after three and six cycles of chemotherapy. CD4 counts and HIV RNA levels were regularly monitored during the course of chemotherapy. RESULTS: Complete remission (CR) was achieved in all patients. Of 12 patients, eight patients received the intended six cycles of BEACOPP. Two patients died of opportunistic infections within the treatment period, one patient died of a relapse after 26 months. The other nine patients remain in CR for their individual follow-up period, median 49 months (range 13-108). The most commonly observed toxicity was bone marrow suppression with National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3/4 leukopenia in 75% of all cases. The mean decline of CD4+ lymphocytes was 238 +/- 230/ micro l, with a mean recovery of 272 +/- 329/ micro l 6 months after the last cycle. Plasma levels of HIV RNA increased moderately or even declined under chemotherapy if highly active anti-retroviral therapy was given concomitantly with BEACOPP. CONCLUSIONS: The BEACOPP regimen is feasible and highly effective in HIV-HD patients. With respect to its overall moderate toxicity, BEACOPP is a safe regimen even in the immunocompromised patient.

Superior virological efficacy of ritonavir-boosted protease inhibitor regimens compared to single protease inhibitor therapy.

Low dose-ritonavir boosted protease inhibitors are increasingly being used for the first-line antiretroviral treatment, though their virological efficacy has just poorly been compared to alternative antiretroviral therapies. Here, we retrospectively investigated the virological responses of 316 protease inhibitor-naive HIV patients receiving highly active antiretroviral treatment based on a single (n = 256) or a ritonavir-boosted protease inhibitor (n = 60), both in the background of two nucleoside analogues. - By intent-to-treat analysis, a complete initial virological response was achieved in 71.8% of all patients in the single protease inhibitor group (indinavir: 76%, ritonavir: 67.5%, nelfinavir: 70.6%) and in 88.3% (p = 0.008) of patients treated with a boosted protease inhibitor (saquinavir/r: 71.4%, indinavir/r: 92.1%, lopinavir/r: 86.6%). The multivariate risk analysis identified boosted PI treatment as an independent predictor of a complete virological response (OR = 2.8, p=0.02). Viral rebound after an initial complete virological response was observed in 28% and 17% (p = 0.06) of patients receiving a single or a dual protease inhibitor, respectively. The rate of durable viral suppression over 12 months was 44.5% and 56.7% (p = 0.09) in the respective study cohorts. Ritonavir-boosted protease inhibitors therefore seem to induce a superior virological response rate and a higher degree of sustained virological suppression.

T-cell non-Hodgkin's lymphoma in adults: clinicopathological characteristics, response to treatment and prognostic factors.

T-cell NHL represent 10-15% of all malignant lymphomas making systematic prospective clinical trials difficult. Therefore, the prognostic significance of the T-cell phenotype has been a matter of controversy in recent years. In a retrospective analysis of 681 patients (pts) with NHL accrued from 1992 to 1997 at a single institution, 66 patients with T-cell NHL were identified. According to the REAL classification, histologies were as follows: 28 peripheral T-cell lymphomas (PTCL), 19 large cell anaplastic lymphoma (LCAL), 12 precursor lymphoblastic lymphoma (Lb), and seven AILD. Multiagent anthracycline containing regimens were used as initial therapy in 91% of cases. T-cell NHL represent 9.8% of all NHL patients at our institution accrued over a 6-year period. Overall response rate was 76%, 21% had progressive disease and 3% died during first line treatment. Mean overall survival (OS) was 8.22 +/- 0.94 years. There was a significant difference in OS between the four different histological subgroups (log rank P=0.0288). LCAL: mean OS 11.05 +/- 1.55 years (95% CI 8.00-14.09); LB: mean OS 7.09 +/- 1.40 years (95% CI 4.33-9.84); PTCL: mean 6.62 +/- 1.17 years (95% CI 4.33-8.90); AILD: 1.54 +/- 0.44 years (95% CI 0.67-2.40). OS was also significantly different for patients classified according to the International Prognostic Index (IPI)-score (log rank P = 0.002). Mean OS for patients with low risk, intermediate low risk, intermediate high risk and high risk was 10.46 +/- 1.02, 6.46 +/- 1.79, 4.50 +/- 1.20 and 1.15 +/- 0.46 years, respectively. Univariate analysis (log-rank test) for prognostic factors also revealed elevated LDH, B-symptoms and extranodal involvement as significant factors for OS. The presence of bulky disease (>7.5 cm), advanced stage III/IV and bone marrow involvement did not influence OS. In conclusion, it is evident that histological subtype and IPI-score have a strong prognostic impact on OS in pts with T-cell NHL. Thus, the distribution of risk factors in patients with T-cell NHL may be more important for OS than T-cell histology per se.