Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients.

Bosutinib is a second-generation tyrosine kinase inhibitor (2GTKI) approved at 400 mg once daily (QD) as first-line therapy in patients with chronic myeloid leukemia (CML) patients and at 500 mg QD in patients who are resistant to or intolerant of prior therapy. In clinical practice, bosutinib is often given to patients who have failed imatinib, nilotinib, and dasatinib (i.e., as fourth-line treatment), despite the limited data on its clinical benefit in this setting. We have retrospectively evaluated the results of bosutinib in a series of 62 CML patients who have failed to prior treatment with all three, imatinib, nilotinib, and dasatinib. Median time on TKI treatment before bosutinib start was 105 (9-163) months, and median duration on bosutinib was 9 months (1-30). Overall, probabilities to achieve complete cytogenetic response (CCyR) and major molecular response (MMR) were 25% and 24% respectively. After a median follow-up period of 14 months, the event-free survival and progression-free survival were 68 and 85%, respectively. Sixty-four percent of patients in CCyR at the time of bosutinib start were able to achieve MMR. In contrast, patients without CCyR, probabilities to obtain CCyR and MMR were 25% and 14%. Bosutinib was well tolerated in this heavily pretreated patients' cohort. Pleural effusions and diarrhea were the most frequent grade II-IV side effects, leading to treatment discontinuation in 16% of patients. Bosutinib is an effective treatment option for patients who have failed previous 2GTKIs due to intolerance. However, efficacy seems to be related to the molecular response that the patient achieved prior to bosutinib.

The antibiotic of choice determined by antibiogram in maxillary sinus elevation surgery: a clinical study.

OBJECTIVES: This study set out to make antibiograms of positive bacteria cultures in samples collected when performing maxillary sinus elevations to determine a specific and effective antibiotic in each case. MATERIAL AND METHODS: A total of 174 patients (90 women and 84 men) with a mean age of 55.92 years underwent 227 sinus elevations. As the membrane was lifted, a sample was collected from the maxillary sinus floor with a cotton swab and placed on a blood agar and chocolate agar culture to incubate for 48 h at 37°; the samples then underwent microbiological analysis. Antibiograms were made for each positive culture to identify the most sensitive antibiotic, which were regrouped according to their mechanism of action as: beta-lactam (penicillins), beta-lactam (cephalosporins), macrolides, quinolones, fosfomycin, aminoglycosides, or trimethoprim-sulfamethoxazole. RESULTS: Of 227 cultures, 18.1% were bacteria-positive. Of the germs, 45% were of the Streptococcus genus, most of which belonged to the Streptococcus viridans group (61.1%). The germs studied showed greater resistance to macrolides and greater sensitivity to penicillins, cephalosporins, and ciprofloxacin. The antibiotics that showed the greatest efficacy were as follows: ampicillin, amoxicillin-clavulanate, and ciprofloxacin. CONCLUSIONS: On the basis of antibiograms of positive cultures, the antibiotics presenting the greatest efficacy against possible complications were as follows: ampicillin, amoxicillin-clavulanate, and ciprofloxacin. Clinically, the antibiograms proved useful as they allowed the prescription of specific antibiotics to resolve possible postoperative sinus infections.

GEM2005 trial update comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?

Melphalan (M), in combination with prednisone (MP), has been the backbone of new combinations, including bortezomib plus MP (VMP). However, new alkylator-free schemes, such as lenalidomide plus low-dose dexamethasone, are challenging the role of alkylators in myeloma treatment of elderly patients. Here we have updated, after a long follow-up (median 6 years), the results of the GEM2005 study that addressed this question by comparing VMP with bortezomib plus thalidomide and prednisone (VTP) as induction. Between April 2005 and October 2008, 260 patients were randomized to receive 6 cycles of VMP or VTP as induction. The median progression-free survival was 32 months for the VMP and 23 months for the VTP arms (P 5 .09). VMP significantly prolonged the overall survival (OS) compared with VTP (median of 63 and 43 months, respectively; hazard ratio [HR]: 0.67, P 5 .01). Achieving immunophenotypic complete response was associated with a significantly longer OS, especially in the VMP arm (66%remain alive after 8 years). Melphalan, plus bortezomib, should be maintained as standard care for the treatment of elderly multiple myeloma patients. This trial was registered at www.clinicaltrials.gov as #NCT00443235.

Bacterial influence on consolidation of bone grafts in maxillary sinus elevation.

OBJECTIVES: The aim of this study was to identify microorganisms present on the maxillary sinus floor at the moment of sinus elevation surgery and, using tomography, to investigate the repercussions these might have for regenerated bone 9 months after the procedure. MATERIALS AND METHODS: 174 patients (90 women and 84 men) with a mean age of 55.92 years underwent 227 sinus elevations (120 left sinus, 107 right sinus). As the membrane was lifted, a sample of the maxillary sinus floor was collected with a cotton swab, and placed on a blood agar and chocolate agar culture to incubate for 48 h at 37°C; the samples then underwent microbiological analysis. Orthopantomographs and computerized tomographs were made immediately after the sinus grafting and after 9 months to measure the amount of remaining and regenerated bone in vertical and transversal direction. RESULTS: 18.1% of 227 cultures were bacteria-positive. 45% of the germs were of the Streptococcus genus, most of which belonged to the S. viridans group (61.1%). Patients presenting negative cultures had 5% more regenerated bone than patients with bacteria-positive cultures, which represents an additional 2.28 mmof vertical bone (with a confidence interval between 0.83 mm and 3.73 mm). CONCLUSIONS: Patients with bacteria-positive cultures obtained previously to the sinus grafting procedure have greater risk of bone height loss after 9 months, which indicates that bacterial contamination may influence bone graft regeneration.

Update of Surgical Techniques for Maxillary Sinus Augmentation: A Systematic Literature Review.

OBJECTIVE: A wide range of surgical techniques are available for maxillary sinus augmentation. This review aimed to determine which techniques have achieved the highest success rates and so offer the greatest predictability. MATERIALS AND METHODS: A systematic literature review was performed using the PubMed, MEDLINE, and Scopus databases, identifying clinical trials that assessed different surgical techniques for maxillary sinus augmentation, and registered the success rates of subsequent implant placement. RESULTS: A total of 40 articles described clinical studies involving different maxillary sinus augmentation procedures with follow-up periods of at least 6 months after dental implant placement. Implant success rates varied between 94% and 100% during the follow-up periods. CONCLUSION: A wide variety of clinical techniques are available for maxillary sinus augmentation; the choice of the technique will depend chiefly on the characteristics of the edentulous site, which will permit or prevent the placement of the implant at the moment of sinus augmentation surgery.

Hepatitis E seroprevalence in inflammatory bowel disease.

BACKGROUND AND AIMS: Several cases of chronic infection by hepatitis E virus (HEV) in immunocompromised patients have been described recently. Patients with inflammatory bowel disease (IBD) are frequently immunocompromised because of the disease itself or due to therapy. Our aims were to determine HEV seroprevalence in patients with IBD and to detect possible chronic forms. METHODS: We prospectively selected a random sample of 87 patients from our local IBD clinic database at the Gastroenterology Service, Hospital Ramón y Cajal, in Madrid, Spain. Patients completed an oral epidemiologic interview. Anti-HEV IgG and IgM antibodies and HEV-RNA were determined. Medical records were reviewed, focusing on drug exposure. RESULTS: We included 87 patients, with a mean age of 44.7 years (SD 16) and a mean of 10.4 years (SD 8.4) with IBD. Fifty-seven percent were diagnosed with Crohn's disease, 41.4% with ulcerative colitis and 1.1% with unclassified IBD. A total of 41.4% had received systemic glucocorticoids for more than 3 months, 32.2% had been treated with thiopurines, 16.1% with biological drugs, and 3.4% with methotrexate. Anti HEV-IgM was determined in 75 patients and IgG in 80, and were positive in 2.7% and 1.3%, respectively. HEV-RNA was analyzed in a random subset of 46 patients, and all determinations were negative. Therefore, no case of chronic HEV infection was detected. CONCLUSIONS: We found a low HEV seroprevalence of just 1.14% in patients with IBD, similar to that in the general population. This could be due to the lower degree of immunosuppression in this group, or to different dietary habits.

Bosutinib shows low cross intolerance, in chronic myeloid leukemia patients treated in fourth line. Results of the Spanish compassionate use program.

The role of bosutinib as rescue treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) patients after failing three previous tyrosine kinase inhibitors (TKIs) is currently unknown. We report here the largest series (to our knowledge) of patients treated with bosutinib in fourth-line, after retrospectively reviewing 30 patients in chronic phase, and pretreated with imatinib, nilotinib, and dasatinib. With a median follow up of 11.1 months, the probability to either maintain or improve their CCyR response was 56.6% (17/30) and 11 patients (36.7%) achieved or maintained their baseline MMR. In patients not having baseline CCyR, the probabilities of obtaining CCyR, MMR, and MR4.5 were 13, 11, and 14%, respectively. The probabilities of obtaining MMR and deep molecular response MR4.5 in patients with baseline CCyR were 40.0% (6/15) and 20.0% (3/15). At 20 months, progression-free survival was 73%. Grade 3-4 hematological toxicities were more frequent in resistant than intolerant patients (45.4 vs. 0.0%). Nonhematological toxicities were also more frequent in resistant patients, being diarrhea the most conspicuous one. Bosutinib seems to be an appropriate treatment option for patients resistant or intolerant to three prior TKI's.

Fibrosis Regression Explains Differences in Outcome in HIV-/HCV-Coinfected Patients with Cirrhosis After Sustained Virological Response.

BACKGROUND AND AIMS: Fibrosis regression (FR) after sustained virological response (SVR) should produce a better outcome in hepatitis C (HCV)-/HIV-coinfected patients with liver cirrhosis, but there are no specific data in this issue. METHODS: We compared the incidence rate (IR) and the time to develop a liver complication and death in 133 cirrhotic patients according to SVR or/and FR. RESULTS: Of 42 patients with SVR, 23 (55%) had FR, in comparison with only 14 of the 91 (15%) without SVR. During a follow-up of 6.8 years (916.8 person-years), the IR of death, liver-related death, and liver-related complications were 2.45, 0.61, and 1.22 per 100 persons/year among SVR/FR, and 7.6, 5.9, and 6.81 among non-SVR without FR (p < 0.01), respectively. SVR patients without FR had also a lower rate of liver-related complications (1.78 vs 3.25; p = 0.02), but a worse IR of death (5.36) and liver-related death (2.68) than non-SVR patients with FR (1.3, and 0.65; p < 0.01). Moreover, FR was associated with less hospital admissions and decreasing alpha-fetoprotein levels. In Cox analysis, only FR was associated with a lower risk of death (adjusted hazard ratio, HR 0.36; 95% CI 0.15-0.86), and liver-related death (HR 0.15; 95% CI 0.03-0.65), whereas both FR (HR 0.09; 95% CI 0.03-0.3, p < 0.01) and SVR (HR 0.24; 95% CI 0.07-0.87) decreased the risk of liver-related complications. CONCLUSION: Fibrosis regression after SVR is associated with the highest reduction in death of any cause, liver-related mortality, and liver-related complications in HIV-/HCV-coinfected patients with cirrhosis.

Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial.

Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235.

Safety and anti-HCV effect of prolonged intravenous silibinin in HCV genotype 1 subjects in the immediate liver transplant period.

BACKGROUND & AIMS: Reinfection of the graft is the rule in patients with HCV cirrhosis undergoing liver transplantation, and HCV-RNA reaches pre-transplantation levels within the first month. Short-term intravenous silibinin monotherapy is safe and shows a potent in vivo anti-HCV effect. We aimed at evaluating the safety and antiviral effect of prolonged intravenous silibinin, started immediately before liver transplantation. METHODS: Single centre, prospective, pilot study, to assess the safety and effect on HCV-RNA kinetics during at least 21 days of intravenous silibinin monotherapy (20 mg/kg/day) in 9 consecutive HCV genotype 1 subjects, in comparison to a control, non-treated group of 7 consecutive prior transplanted subjects under the same immunosuppressive regimen (basiliximab, steroids, delayed tacrolimus, micophenolate). RESULTS: Intravenous silibinin led to significant, maintained and progressive HCV-RNA decreases (mean HCV-RNA drop at week 3, -4.1 ± 1.3 log(10)IU/ml), and lack of viral breakthrough during administration. Four patients (44%) reached negative HCV-RNA, maintained during silibinin treatment, vs. none in the control group, but HCV-RNA relapsed in all of them after a median of 21 days (16-28), following silibinin withdrawal. Partial responders to silibinin showed marked decreases in HCV-RNA when compared to controls, but lower than complete responders. There were no clinical adverse effects, and silibinin led to asymptomatic transient hyperbilirubinemia (week 2, 4.2 ± 2.2 vs. 2.5 ± 3.6 mg/dl; p=0.02). CONCLUSIONS: Prolonged intravenous silibinin monotherapy was safe in the immediate liver transplantation period, leading to a potent and time dependent antiviral effect and lack of HCV-RNA breakthrough during administration. However, HCV-RNA rebounded after withdrawal, and silibinin monotherapy did not avoid reinfection of the graft.

Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance.

Cytogenetic abnormalities (CAs) such as t(4;14), t(14;16) or del(17p), and nonhyperdiploidy are associated with poor prognosis in multiple myeloma. We evaluated the influence of CAs by FISH and DNA ploidy by flow cytometry on response and survival in 232 elderly, newly diagnosed multiple myeloma patients receiving an induction with weekly bortezomib followed by maintenance therapy with bortezomib-based combinations. Response was similar in the high-risk and standard-risk CA groups, both after induction (21% vs 27% complete responses [CRs]) and maintenance (39% vs 45% CR). However, high-risk patients showed shorter progression-free survival (PFS) than standard-risk patients, both from the first (24 vs 33 months; P = .04) and second randomization (17 vs 27 months; P = .01). This also translated into shorter overall survival (OS) for high-risk patients (3-year OS: 55% vs 77%; P = .001). This adverse prognosis applied to either t(4;14) or del(17p). Concerning DNA ploidy, hyperdiploid patients showed longer OS than nonhyperdiploid patients (77% vs 63% at 3 years; P = .04), and this was more evident in patients treated with bortezomib, thalidomide, and prednisone (77% vs 53% at 3 years; P = .02). The present schema does not overcome the negative prognosis of high-risk CAs and nonhyperdiploidy. This trial was registered with www.ClinicalTrials.gov as NCT00443235.

Salivary Markers of Oxidative Stress in Patients Undergoing Orthodontic Treatment with Clear Aligners versus Self-Ligating Brackets: A Non-Randomized Clinical Trial.

The aim of this work was to determine advanced the oxidative protein products (AOPPs), total antioxidant capacity (TAC), and myeloperoxidase activity (MPO) in the saliva of patients undergoing orthodontic treatment with clear removable aligners in comparison with another group in treatment with fixed passive self-ligating brackets applying light forces, before treatment, after 30 days, and after 90 days of treatment. This non-randomized clinical trial recruited patients consecutively, all of which were over 18 years of age and due to undergo orthodontic treatment. They were divided into two groups according to treatment type: Group A, 48 patients treated with clear aligners (Invisalign®); and Group B, 19 patients treated with Damon System® 0.22″ self-ligating brackets applying light forces. Saliva samples were collected by a single clinician following the same protocol and underwent three analyses-AOPPs, TAC, and MPO levels-at baseline before placing the apparatus, after 30 days, and after 90 days treatment. Orthodontic treatment, whether with clear aligners or fixed self-ligating brackets and light forces, increased AOPPs after the first 30 days of treatment. During the initial phases of orthodontic treatment, neither clear aligners nor fixed self-ligating brackets applying light forces showed changes in TAC and MPO. Orthodontic treatment with both clear aligners and fixed apparatus self-ligating brackets applying light forces increases oxidative stress (AOPPs) after the first 30 days of treatment. There are no differences in AOPP levels between treatment with clear aligners and self-ligating brackets during the first 90 days of treatment. The antioxidative capacity of saliva during the initial phases of orthodontic treatment, whether with self-ligating brackets or clear aligners, does not undergo significant changes. With either orthodontic technique, the patients' salivary antioxidant capacity is similar.

[Evaluation of a prototype real-time PCR assay for the separate detection of human papilloma virus genotypes 16 and 18 and other high risk human papillomavirus in cervical cancer screening]. / Evaluación de un sistema de PCR a tiempo real (cobas 4800) para la detección separada de los genotipos 16 y 18 y otros genotipos de alto riesgo del virus del papiloma humano en la prevención del cáncer cervical.

BACKGROUND: It has recently been confirmed that detection of DNA of human papilloma virus (HPV) is more useful than cytology in the screening for cervical cancer, especially if genotypes 16 and 18 are identified. Cobas 4800 is an automated system that detects 14 high risk HPV genotypes: genotypes 16 and 18 separately and 12 other high-risk genotypes pooled. OBJECTIVES: The aim of this study is to compare the performance of the cobas 4800 HPV test against the hybrid capture 2 (HC2) and particularly in women in whom>CIN2 lesions are detected. PATIENTS AND METHODS: Aliquots from 412 cervical specimens have been studied with three different assays, real time PCR (cobas 4800), Linear Array HPV test, and HC2. Cytological and histological results were also available. RESULTS: There was good agreement between the cobas 4800 and HC2 results in 376 of the 412 women (kappa 0.85). Where there was not good agreement, low-risk HPV genotypes were detected by linear array in the majority of samples positive by HC2 and negative by the cobas 4800. Sensitivity and specificity for detecting>CIN2 lesions were 92.5 and 44%, respectively, by cobas 4800, and 88 and 51% by hybrid capture. CONCLUSIONS: In this evaluation the cobas 4800 HPV test was shown to have a similar performance to the HC2 test. However HC2 was less specific due to cross reactivity with low risk genotypes, mainly genotype 53. Cobas 4800 is very reliable in the detection of high-risk genotypes, with the advantage of simultaneously providing information regarding genotype16 and 18 infections.

Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial.

BACKGROUND: Bortezomib plus melphalan and prednisone (VMP) is significantly better than melphalan plus prednisone alone for elderly patients with untreated multiple myeloma; however, toxic effects are high. We investigated a novel and less intensive bortezomib-based regimen to maintain efficacy and to reduce toxic effects. METHODS: Between March, 2006, and October, 2008, 260 patients with untreated multiple myeloma, 65 years and older, from 63 Spanish centres, were randomly assigned to receive six cycles of VMP (n=130) or bortezomib plus thalidomide and prednisone (VTP; n=130) as induction therapy, consisting of one cycle of bortezomib twice per week for 6 weeks (1·3 mg/m² on days 1, 4, 8, 11, 22, 25, 29, and 32), plus either melphalan (9 mg/m² on days 1-4) or daily thalidomide (100 mg), and prednisone (60 mg/m² on days 1-4). The first cycle was followed by five cycles of bortezomib once per week for 5 weeks (1·3 mg/m² on days 1, 8, 15, and 22) plus the same doses of melphalan plus prednisone and thalidomide plus prednisone. 178 patients completed the six induction cycles and were randomly assigned to maintenance therapy with bortezomib plus prednisone (n=87) or bortezomib plus thalidomide (n=91), consisting of one conventional cycle of bortezomib for 3 weeks (1·3 mg/m² on days 1, 4, 8, and 11) every 3 months, plus either prednisone (50 mg every other day) or thalidomide (50 mg per day), for up to 3 years. Treatment codes were generated with a computerised random number generator, and neither participants nor study personnel were masked to treatment. The primary endpoint was response rate in induction and maintenance phases. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00443235. FINDINGS: In the induction phase, 105 (81%) patients in the VTP group and 104 (80%) in the VMP group achieved partial responses or better (p=0·9), including 36 (28%) and 26 (20%) complete remissions, respectively (p=0·2). Treatment with VTP resulted in more serious adverse events (40 [31%] vs 20 [15%], p=0·01) and discontinuations (22 [17%] vs 15 [12%], p=0·03) than did treatment with VMP. The most common toxicities (grade 3 or worse) were infections (one [1%] in the VTP group vs nine [7%] in the VMP group), cardiac events (11 [8%] vs 0), and peripheral neuropathy (nine [7%] vs 12 [9%]). After maintenance therapy, the complete remission rate was 42% (40 [44%] patients in complete remission in the bortezomib plus thalidomide group, 34 [39%] in the bortezomib plus prednisone group). No grade 3 or worse haematological toxicities were recorded during maintenance therapy; two (2%) patients in the bortezomib plus prednisone group and six (7%) in the bortezomib plus thalidomide group developed peripheral neuropathy. INTERPRETATION: Reduced-intensity induction with a bortezomib-based regimen, followed by maintenance, is a safe and effective treatment for elderly patients with multiple myeloma. FUNDING: Pethema (Spanish Program for the Treatment of Hematologic Diseases).

Hepatitis C virus infection acquired in childhood.

Hepatitis C virus (HCV) infection occurs less frequently in children than in adult patients, and the natural history, prognosis, and clinical significance of HCV infection in children are poorly defined. We report here a descriptive follow-up of the clinical course, biochemical data, and viral markers observed in 37 children with anti-HCV. Ten patients included in the study tested persistently negative for serum HCV-RNA (group 1) and 27 patients tested persistently positive (group 2). In group 1, serum alanine aminotransferase (ALT) was normal in all patients, while two patients had non-organ-specific autoantibodies. In group 2, serum ALT was elevated in 13 of 27 patients, and five patients had non-organ-specific autoantibodies. HCV genotype 1a and 1b were the most prevalent among HCV-RNA-positive patients. Twenty liver biopsies were carried out on 17 patients in our series (mean evolution time, 11.2 years; range, 3-21 years). The liver specimens showed mild necroinflammatory changes in most patients, and fibrosis was absent or low grade. Two HCV-RNA-positive patients became persistently HCV-RNA negative. Of the 26 children investigated, 7 (one in group 1, six in group 2) had a co-infection with hepatitis G virus. Conclusion Most children chronically infected with HCV were asymptomatic and presented only mild biochemical evidence of hepatic injury. Autoimmunity in the form of non-organ-specific autoantibodies was common. HCV in children induced mild changes in the liver with a low level of fibrosis and at a low rate of progression.

Relevance of cutoff on a 4th generation ELISA performance in the false positive rate during HIV diagnostic in a low HIV prevalence setting.

BACKGROUND: Despite the high specificity of fourth-generation enzyme immunoassays (4th-gen-EIA) for screening during HIV diagnosis, their positive predictive value is low in populations with low HIV prevalence. Thus, screening should be optimized to reduce false positive results. OBJECTIVES: The influence of sample cutoff (S/CO) values by a 4th-gen-EIA with the false positive rate during the routine HIV diagnosis in a low HIV prevalence population was evaluated. STUDY DESIGN: A total of 30,201 sera were tested for HIV diagnosis using Abbott Architect® HIV-Ag/Ab-Combo 4th-gen-EIA at a hospital in Spain during 17 months. Architect S/CO values were recorded, comparing the HIV-1 positive results following Architect interpretation (S/CO≥1) with the final HIV-1 diagnosis by confirmatory tests (line immunoassay, LIA and/or nucleic acid test, NAT). ROC curve was also performed. RESULTS: Among the 30,201 HIV performed tests, 256 (0.85%) were positive according to Architect interpretation (S/CO≥1) but only 229 (0.76%) were definitively HIV-1 positive after LIA and/or NAT. Thus, 27 (10.5%) of 256 samples with S/CO≥1 by Architect were false positive diagnose. The false positive rate decreased when the S/CO ratio increased. All 19 samples with S/CO ≤10 were false positives and all 220 with S/CO>50 true HIV-positives. The optimal S/CO cutoff value provided by ROC curves was 32.7. No false negative results were found. CONCLUSIONS: We show that very low S/CO values during HIV-1 screening using Architect can result HIV negative after confirmation by LIA and NAT. The false positive rate is reduced when S/CO increases.

[Acute hepatitis E in Madrid: description of 18 cases]. / Hepatitis aguda E en Madrid: descripción de 18 casos.

INTRODUCTION: Hepatitis E virus (HEV) is the main cause of non-A non-B enterically transmitted hepatitis in underdeveloped countries but is rare in industrialized areas. However, in the last few years, several sporadic autochthonous hepatitis E cases have been reported in Europe and no risk factors, such as visiting to endemic areas, could be found in these patients. OBJECTIVE AND PATIENTS: Twelve patients with sporadic autochthonous hepatitis E (no risk factors such as traveling to endemic areas) and six imported cases (travel to Nepal, Santo Domingo, China, Brazil and Ecuador) were studied between June 1999 and December 2005. RESULTS: HEV infection was diagnosed in patients with symptoms of acute hepatitis and the presence of IgG and IgM antibodies in serum with no other markers of hepatitis. HEV infection is probably overlooked in industrialized countries. CONCLUSIONS: This diagnosis should be suspected in patients with acute hepatitis and anti-HEV antibodies in serum without known risk factors such as traveling to endemic areas.

Dried blood as an alternative to plasma or serum for Trypanosoma cruzi IgG detection in screening programs.

Trypanosoma cruzi serological screening is recommended for people potentially exposed to this parasite in countries where Trypanosoma cruzi is endemic and those where it is not endemic. Blood samples on filter paper may be a practical alternative to plasma/serum for antibody detection. Using the Architect Chagas assay, we detected the presence of IgG against T. cruzi in matched serum and dried blood spots (DBS) collected from 147 patients residing in Madrid, Spain, who had potential previous exposure to T. cruzi. The κ statistic for the DBS/serum proportion of agreement for the detection of antibodies against T. cruzi was 0.803, considering an S/CO (assay result unit; chemiluminescent signal from the sample [S] divided by the mean chemiluminescent signal for the three calibrators used in the test [CO]) cutoff value of ≥1.00. The relative sensitivity of the Architect test using DBS increased from 95.2% to 98.8% when the cutoff was lowered from ≥1.00 to ≥0.88, while the relative specificity decreased from 84.1% to 71.6%. Overall, the median S/CO values for DBS were significantly lower than those for serum (2.6 versus 6.5; P < 0.001). Discrepancies that occurred with the use of DBS included 10 false positives (with low S/CO values in 9 cases [median, 2.13]) and 4 false negatives, with mean S/CO values of 0.905 (gray zone). Using DBS plus a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) may be a simple and reliable method for detecting IgG against T. cruzi when blood sampling by venipuncture is not feasible. This method may also reduce the false-negative rates observed with some rapid diagnostic tests. The lower relative sensitivity compared to the reference method may be increased by lowering the optical density threshold.