An Audit of Efficacy and Toxicity of Teicoplanin Versus Vancomycin in Febrile Neutropenia: Is the Different Toxicity Profile Clinically Relevant?

Abstract Background: Glycopeptides are often used for persistent fever in neutropenic patients. This study compares efficacy and toxicity of teicoplanin and vancomycin. Patients and Methods: Hundred consecutive neutropenic patients with hematological malignancies and persistent fever after 72 h of first-line antibiotic therapy (91% piperacillin/tazobactam) were treated with teicoplanin (800 mg on day 1, then 400 mg/day) + piperacillin/tazobactam + gentamicin from 08/96 to 09/00 (group T) or with vancomycin (2 g/day) + meropenem + levofloxacin from 10/00 to 04/02 (group V). Success was defervescence (≥ 7 days) in absence of any sign of continuing infection. Nephrotoxicity was monitored daily as increase in serum creatinine. Results: Fifty patients were analyzed in each group. Efficacy was evaluated in patients with piperacillin/tazobactam as first-line therapy only. Treatment was successful in 76% in group T (n = 42) and 59% in group V (n = 49), p = 0.118. Toxicity was evaluated in all patients. The median increase of creatinine was 11% (interquartile range 0%–30%) in group T and 17% (0%–74%) in group V, p = 0.062. In patients who received concomitant amphotericin B (given for 7 days and 6 days, respectively, p = 0.525), median creatinine increased from 0.9 mg/dl (0.8–1.1) to 1.2 mg/dl (0.9–1.5) in group T and from 0.9 mg/dl (0.8–1.08) to 1.55 mg/dl (1.33–2.23) in group V (p < 0.001). This led to a doubling of creatinine in 2/23 (9%) patients of group T and in 9/16 (56%) patients of group V (p = 0.003). A multivariate analysis revealed that concomitant use of amphotericin B (p < 0.001) and treatment with vancomycin (p = 0.002) were independently associated with nephrotoxicity. Conclusion: Teicoplanin and vancomycin were comparably effective in patients with neutropenia and persistent fever, but – if combined with amphotericin B – vancomycin was significantly more nephrotoxic than teicoplanin.     

Significance of genotype in tetrahydrobiopterin-responsive phenylketonuria

Summary Background  The value of genotyping to identify tetrahydrobiopterin-responsive (BH₄-responsive) patients with phenylalanine hydroxylase (PAH) deficiency is a matter of debate. Methods  We reviewed 250 cases of patients with PAH deficiency, using published data from 198 cases and unpublished data from 52 cases of patients attending our own clinic. Patients underwent analyses for BH₄ load and genetic mutations. Partial and full BH₄ responses were defined as a 10–29% decrease and a ≥30% decrease from baseline in blood phenylalanine levels, respectively. BH₄-responsive alleles were identified from BH₄-responsive patients as either homozygous for a specific allele or compound heterozygous for that allele with a null mutation. Results  Most inconsistencies between observed genotype and BH₄ response were associated with mutations in the regulatory domain of PAH (p.R68S, p.I65T, p.L48S and p.F39C), where 20/62 alleles (32.2%) were non-responsive. In the catalytic domain (mutations p.Y414C, p.R261Q, p.E390G, p.A300S, p.R241C, p.A403V and p.V388M), only 8/125 alleles (6.4%) were non-responsive. Seven patients had a genotype with two BH₄-responsive alleles resulting in no response or only a partial response to BH₄. Ten patients had identical genotypes but inconsistent responses in BH₄ load. Conclusions  These results show that BH₄ non-responsiveness is associated with genotype. However, patients with mutations in the regulatory domain show inconsistent results. In patients with two responsive alleles, non-responsiveness may be related to negative inter-allelic complementation. In patients with the same genotype and inconsistent results for BH₄ load, external factors such as intestinal absorption of BH₄, catabolic conditions or other genetic factors may be responsible. Further in vitro studies are necessary to clarify the genotype–phenotype correlation in patients with BH₄-responsive PKU. Competing interests: F. K. Trefz is a member of the scientific advisory board for PKU supported by Merck Serono International S.A., Geneva, Switzerland (an affiliate of Merck KGaA, Darmstadt, Germany). Presented at the International Conference on Tetrahydrobiopterin, PKU, and NOS, 23–28 March 2008, St Moritz, Champfér, Switzerland     

Radiographic hand osteoarthritis and serum levels of osteocalcin: cross-sectional study

The objective of this study is to evaluate the association between radiographic hand osteoarthritis and serum level of osteocalcin. The study population comprised Chuvashians (285 males, age 47.38 ± 16.79; 265 females, age 48.55 ± 15.94 years). OA was evaluated for 14 joints of each hand using Kellgren and Lawrence (K–L), joint space narrowing (JSN) and osteophytes (OS) scores. Plasma-intact osteocalcin was measured in 550 individuals by immunoradiometric assay using ELSA-OSTEO kit. Statistical analyses included multiple linear and logistic regressions. 51.64% of studied individuals had at least one finger joint affected at K–L ≥2 level. JSN at the level ≥2 was found in 9.82% and OS ≥2 was found in 35.09% of the studied individuals. Osteocalcin showed a modest, but statistically significant, association with the number of affected joints according the K–L scale (beta = 0.082, p = 0.015), JSN scale (beta = 0.097, p = 0.025) and OS scale (beta = 0.078, p = 0.029). No significant association was found between the presence of at least one affected joint (K–L ≥ 2 or OS ≥ 2) and serum level of osteocalcin. Presence of at least one joint with space narrowing ≥2 was significantly associated with serum level of osteocalcin (beta = 0.052, p = 0.023). In this cross-sectional population-based study, we found that serum level of osteocalcin is positively associated with severity of hand OA, measured by K–L, JSN and OS scales.     

Transanale endoskopische mikrochirurgische Exzision von pT2-Rektumkarzinomen

Zusammenfassung Fragestellung und Hintergrund: In früheren Studien wurde die lokale Exzision vorwiegend als Eingriff bei „low-risk“ pT1-Rektumkarzinomen propagiert. Die Ergebnisse bei T2-Tumoren sind unklar; es wurden Rezidivraten von 0–67% berichtet. Diese Studie wurde durchgeführt, um den Wert der lokalen Exzision bei T2-Rektumkarzinomen, prognostische Faktoren sowie die Notwendigkeit von Nachoperationen zu bestimmen. Patienten und Methodik: Nach einer lokalen Exzision bei 649 Patienten mit Rektumkarzinomen wurden bei 44 Patienten pT2-Karzinome gefunden. Im Allgemeinen wurde eine sofortige Nachoperation empfohlen; allerdings lehnten 24 Patienten eine weitere Operation ab oder wurden aufgrund von Begleiterkrankungen nicht operiert. Die Ergebnisse wurden getrennt analysiert für lokale R0-Resektionen von „low-risk“ Karzinomen sowie für prognostisch ungünstige Kriterien (R1/RX/R ≤ 1 mm/G3–4/L1/V1). Nachoperationen wurden innerhalb von 4 Wochen durchgeführt. Rezidive wurden au?erdem entsprechend einer vorausgehenden lokalen R0-Resektion von „low-risk“ Tumoren wie auch ungünstiger Ergebnisse differenziert und in einer Langzeit-Follow-up-Studie analysiert. Patienten mit palliativer Therapie wurden ausgeschlossen, das Follow-up wurde bei 90% erreicht (20 ausschlie?lich transanale endoskopische mikrochirurgische Exzisionen, 17 transanale endoskopische mikrochirurgische Exzisionen und Nachoperationen). Ergebnisse: Die lokalen Rezidivraten nach ausschlie?licher lokaler R0-Resektion von „low-risk“ T2-Karzinomen betrugen 29%, wohingegen Patienten mit ungünstigen Kriterien zu 50% Rezidive entwickelten. Nach einer sofortigen Nachoperation war das lokale Rezidivrisiko bei Patienten ohne Lymphknotenmetastasen signifikant reduziert auf 7%. Schlussfolgerung: Die lokale R0-Resektion bei „low-risk“ pT2-Karzinomen stellt eine unzureichende Therapie dar. Bei pT2N0M0-Rektumkarzinomen kann die Rezidivrate durch sofortige Nachoperation auf ein Level ?hnlich einer prim?ren Radikaloperation reduziert werden. Ein prim?r schlechtes lokales Resektionsergebnis (R1/RX/R ≤ 1 mm/ G3–4/L1/V1) hat keinen negativen Einfluss auf das weitere onkologische Ergebnis. übersetzter Nachdruck aus Dis Colon Rectum 2007;50:292–301; DOI 10.1007/s10350-006-0816-7.     

Risk Factors for Hypoxemia During Ambulatory Gastrointestinal Endoscopy in ASA I–II Patients

Background Most studies identify the American Society of Anesthesiology (ASA) classification as the most significant risk factor for hypoxemia. The risk factors operative within ASA I and II patients are not well defined. Therefore, we analyzed prospectively collected data to identify the risk factors of hypoxemia in such patients. Methods A combination of a narcotic and benzodiazepine was used for sedation and oxygen was supplemented if hypoxemia (oxygen saturation ≤90%) developed. Univariate and multivariate analyses were performed and correlations estimated for predetermined clinical variables. Results 40 of 79 patients (51%) developed hypoxemia, which occurred more frequently in the obese (71%; 10/14) than the nonobese (46%; 30/65) group (P = 0.08). On multivariate analysis, the odds ratios (OR) and 95% confidence intervals (CI) for developing hypoxemia were age ≥ 60 years 4.5 (1.4–14.3) P = 0.01, and incremental 25-mg doses of meperidine 2.6 (1.02–6.6) P = 0.04. Body mass index (BMI) significantly correlated with the number of hypoxemic episodes (rho 0.26, 95% CI 0.04–0.48, P = 0.02). Conclusion In ASA I and II patients, BMI significantly correlated with the number of hypoxemic episodes, whereas age ≥ 60 years and meperidine dose were significant risk factors for hypoxemia.     

Revisiting the oral glucose tolerance test criterion for the diagnosis of diabetes

OBJECTIVE: The Expert Committee on the Diagnosis and Classification of Diabetes retained the 2-hour glucose concentration on an oral glucose tolerance test of ≥11.1 mmol/L (200 mg/dL) as a criterion to diagnose diabetes. Since glycated hemoglobin levels have emerged as the best measure of long-term glycemia and an important predictor of microvascular and neuropathic complications, we evaluated the distribution of hemoglobin A1C (Hb A1C) levels in individuals who had undergone an oral glucose tolerance test to determine how well 2-hour values could identify those with normal versus increased Hb A1C levels. DESIGN: A cross-sectional analysis of 2 large data sets was performed. We cross-tabulated 2-hour glucose concentrations on an oral glucose tolerance test separated into 4 intervals (<7.8 mmol/L [140 mg/dL], 7.8–11.0 mmol/L [140–199 mg/dL], 11.1–13.3 mmol/L [200–239 mg/dL], and ≥13.3 mmol/L [240 mg/dL]) with Hb A1C levels separated into 3 intervals (normal; <1% above the upper limit of normal; and greater than or equal to the upper limit of normal +1%). RESULTS: Approximately two thirds of patients in both data sets with 2-hour glucose concentrations of 11.1 to 13.3 mmol/L (200–239 mg/dL) had normal Hb A1C levels. In contrast, 60% to 80% of patients in both data sets with 2-hour glucose concentrations ≥13.3 mmol/L (240 mg/dL) had elevated Hb A1C levels. CONCLUSION: Since Hb A1C levels are the best measures presently available that reflect long-term glycemia, we conclude that the 2-hour glucose concentration criterion on an oral glucose tolerance test for the diagnosis of diabetes should be raised from ≥11.1 mmol/L (200 mg/dL) to ≥13.3 mmol/L (240 mg/dL) to remain faithful to the concept that diagnostic concentrations of glucose should predict the subsequent development of specific diabetic complications (e.g., retinopathy). Presented at the American Diabetes Association meeting, San Diego, Calif, June 1999.     

The Cardioprotective Effect of a Statin and Cilostazol Combination: Relationship to Akt and Endothelial Nitric Oxide Synthase Activation

Background Atorvastatin (ATV) protects against ischemia-reperfusion by upregulating Akt and subsequently, endothelial nitric oxide synthase (eNOS) phosphorylation at Ser-1177. However, when given orally, high doses of ATV (10 mg/kg/d) are needed to achieve maximal protective effect in the rat. Protein kinase A (PKA) also phosphorylates eNOS at Ser-1177. As PKA activity depends on cAMP, cilostazol (CIL), a phosphodiesterase type III inhibitor, may stimulate NO production by activating PKA. Hypothesis: CIL and ATV may have synergistic effects on eNOS phosphorylation and myocardial infarct size (IS) reduction. Methods Sprague-Dawley rats received 3-day oral pretreatment with: (1) water; (2) low dose ATV (2 mg/kg/d); (3) CIL (20 mg/kg/d): (4) ATV+CIL. Rats underwent 30 min coronary artery occlusion and 4 h reperfusion, or hearts explanted for immunoblotting without being subjected to ischemia. Area at risk (AR) was assessed by blue dye and IS by triphenyl–tetrazolium–chloride. Results Body weight and the size of AR were comparable among groups. There were no significant differences among groups in mean blood pressure and heart rate. CIL, but not ATV, reduced IS. IS in the ATV+CIL group was significantly smaller than the other three groups (P < 0.001 for each comparison). ATV, CIL and their combination did not affect total eNOS expression. ATV at 2 mg/kg/d did not affect Ser-1177 P-eNOS levels, whereas CIL increased it (258 ± 15%). The level of myocardial P-eNOS levels was highest in the ATV+CIL group (406 ± 7%). Conclusions ATV and CIL have synergistic effect on eNOS phosphorylation and IS reduction. By increased activation of eNOS, CIL may augment the pleiotropic effects of statins.     

Safety and Immunogenicity of Early Vaccination with Two Doses of Tetravalent Measles-Mumps-Rubella-Varicella (MMRV) Vaccine in Healthy Children from 9 Months of Age

Abstract Background: This open, randomized, controlled study [208136/018] assessed the safety and immunogenicity of early vaccination with an experimental tetravalent measlesmumps-rubella-varicella (MMRV) vaccine (GlaxoSmithKline Biologicals) compared to concomitant administration of separate licensed MMR (Priorix™) and varicella (Varilrix™) vaccines (MMR+V). Methods: Vaccines were administered as a two-dose course in healthy children at 9 and 12 months of age (N = 153 in the MMRV group and N = 146 in the MMR+V group). Results: The incidence of fever of any intensity (axillary temperature ≥ 37.5 °C) during the 15 days of follow-up post-dose 1 was higher in the MMRV group than in the MMR+V group (48.3% vs 25.7%, respectively) but was low in both groups post-dose 2 (20.3% and 22.1%, respectively). The incidence of fever > 39.0 °C and the incidence of solicited local symptoms (pain, redness, swelling) were low ( ≤ 5.3% and ≤ 13.7%, respectively) in the two groups after each vaccine dose. Seroconversion rates were similar in the two groups for all vaccine antigens after each vaccine dose and were ≥ 99.2% for each antigen post-dose 2. Anti-measles GMT was higher in the MMRV group than in the MMR+V group after the first vaccine dose. After the second dose, slight to moderate increases in measles, mumps and rubella antibody titers and a substantial increase in varicella antibody titer were seen in both groups, leading to higher GMTs in the MMRV group compared with the MMR+V group for measles, mumps and varicella. Anti-rubella antibody GMTs were similar in the two groups post-dose 2. Conclusion: Early vaccination with two doses of this experimental MMRV vaccine at 9 and 12 months of age was well-tolerated and at least as immunogenic as two doses of separate licensed MMR and varicella vaccines.     

Clinical validation of atazanavir/ritonavir genotypic resistance score in protease inhibitor-experienced patients

OBJECTIVE: To develop a clinically relevant genotypic resistance score for boosted atazanavir (ATV) in protease inhibitor-experienced patients. METHODS: At baseline, 62 patients with HIV-1 RNA > 1000 copies/ml switched to a boosted ATV regimen (300 mg ATV, 100 mg ritonavir once daily); two were excluded from analysis at 3 months as they had undetectable plasma ATV. The impact of baseline protease mutations on virological response (> 1 log10 copies/ml plasma HIV RNA decrease) at 3 months was analysed using Fisher's exact test. Mutations with prevalence > 8% and P < 0.2 were retained. Cochran-Armitage's test was used to select the combination of mutations most strongly associated with reduced virological response. Robustness of the score was investigated using bootstrap resampling. RESULTS: At 3 months, 82% of patients had a virological response and 56% had RNA < 50 copies/ml. Eight mutations (10F/I/V, 16E, 33I/F/V, 46I/L, 60E, 84V, 85V and 90M) were retained in the genotypic resistance score (P = 8.67 x 10) and virological response was observed in 100%, 100%, 80%, 42%, and 0% of patients with none, one, two, three, and four/five mutations, respectively. There was 100% response in patients with a score < 2 independently of the number of active drugs, whereas in patients with a score > or = 3 there was a gradient of response according to the number of active drugs (0%, 29% and 60% with none, one and two/three active drugs, respectively). CONCLUSIONS: The occurrence of three of the eight mutations in the ATV/RTV genotypic resistance score predicted a clinically identifiable reduced response in patients.     

Effects of Controlled Voluntary Increase in the Ventilatory Demand on Respiratory System Resistance in Healthy and Non-Cystic Fibrosis Bronchiectasis Subjects: A Cross-Sectional Study

IntroductionBronchiectasis patients may present a reduced functional capacity due to an increase in the ventilatory demand during exercise.ObjectiveTo evaluate the effects of controlled voluntary hyperinflation and increased respiratory rate on the mechanics of the respiratory system, simulating what happens during exercise, in bronchiectasis and healthy subjects.MethodsBronchiectasis (n = 30) and healthy (n = 16) subjects were evaluated by impulse oscillometry (IOS) during a baseline condition, and in controlled conditions with baseline (b) tidal volume (V) and hyperinflation (H), with respiratory rates at 30(R30) and 40(R40) bpm, in a random order. The mixed effects and a significance level at 0.05 were used for comparisons.ResultsResistance at 5 Hz (R5), and at minus 20 Hz (R5–R20), in kPa/L/s, were higher in subjects with bronchiectasis in all experimental conditions (p < 0.05). For the bronchiectasis group, R5 and R5-20 increased with R increase at V (VRb versus VR30 and VR40; VR30 versus VR40; R5, R20 and R5-20 increased with R increase at H (HRb versus HR40; HR30 versus HR40). For the same R, there was a decrease with H compared to V (HRb versus VR30 and VR40; and HR30 versus VR30 and VR40). For the healthy group, only R20 showed differences (HR30 versus HR40; HR40 versus VR40).ConclusionThe tachypnea increases the resistance and reactance of the respiratory system in bronchiectasis patients, and the voluntary hyperinflation caused attenuates this increase. These results can guide the development of strategies to reduce the limitation of physical activity in patients with bronchiectasis.     

Observational Study on HIV-Infected Subjects Failing HAART Receiving Tenofovir Plus Didanosine as NRTI Backbone

Abstract We evaluated the efficacy of tenofovir (TDF) – and didanosine (ddI)-containing backbones in HIV-infected experienced subjects. We included in the study 245 subjects who started a TDF/ddI-containing HAART with HIV-RNA > 3 log₁₀ cp/ml and an available genotypic resistance test at baseline. At baseline, median CD4 counts and HIV-RNA were 278 cell/mmc and 4.32 log₁₀ cp/ml, respectively. Seventy-four subjects (30.2%) discontinued TDF and/or ddI, 23 of them for drug-related toxicities or intolerance. One-hundred and twenty-six (51.4%) subjects achieved virologic success (HIV-RNA < 50 copies/ml in two consecutive determinations) in a median time of 6.1 months; higher HIV-RNA levels (HR: 0.66, 95% CI: 0.54– 0.79, p < 0.001 for each additional log₁₀ copies/ml), and the total number of mutations either for PI and NNRTI at baseline (HR: 0.87, 95% CI: 0.81–0.92, p < 0.001 for each additional mutation) were both predictors of virologic success. M184V was marginally associated with virologic success (HR: 1.34, 95% CI: 0.94–1.90, p = 0.10 vs no M184V), whilst the number of TAMs was not associated. One-hundred-thirty-three (54.3%) subjects achieved immunologic success (increase of ≥ 100 cells/mm³ from baseline) in a median time of 7.5 months; immunologic success was associated with HIV-RNA levels at baseline (HR: 0.91, 95% CI: 0.79–0.98, p = 0.04 for each additional log₁₀ copies/ml), the total number of mutations either for PI or NNRTI (HR: 0.91, 95% CI: 0.85–0.98, p = 0.01 for each additional mutation) and CD4 count at baseline (HR: 1.11, 95% CI: 1.00–1.23, p = 0.05 for each additional 100 cells/mm³). Results obtained by the on-treatment analyses were comparable. In our study, HAART containing TDF/ddI seem associated with a virologic and immunologic response, when such regimens are chosen according to a genotypic resistance test.     

Switch from ritonavir-boosted to unboosted atazanavir guided by therapeutic drug monitoring

Plasma concentration of atazanavir (ATV) may be reduced when coadministered with tenofovir (TDF) or proton pump inhibitors. Boosting ATV exposure with ritonavir (r) may make it possible to overcome these drug interactions. However, jaundice and loss of the metabolic advantages of ATV are more frequent using ATV/r than ATV alone. Herein, we assessed whether therapeutic drug monitoring (TDM) could make it possible to identify the subset of patients in whom removal of ritonavir could be attempted without risk of suboptimal plasma ATV exposure and subsequent virological failure. A total of 56 patients with undetectable plasma HIV-RNA under a stable triple regimen containing ATV 300/100 mg qd were switched to ATV 400 mg qd. Plasma ATV concentrations were measured using a reliable high-performance liquid chromatography method. Median plasma ATV C(min) fell from 880 to 283 ng/ml (p = 0.03) after removal of ritonavir. While all patients on ATV/r showed ATV plasma concentrations within therapeutic values (IC(min) above 150 ng/ml) before switching, four patients (7%) fell below this threshold after switching to ATV 400 mg qd. However, only one of this group experienced virological failure at week 24 of follow-up. TDF was part of the antiretroviral regimen in all four cases. From a total of 29 (52%) patients on ATV/r showing grade 3-4 hyperbilirubinemia, only 7 (12%) remained on it upon switching to ATV 400 mg qd (p < 0.001). Patients with complete viral suppression under ATV/r 300/100 mg qd may benefit from switching to ATV 400 mg qd guided by TDM, which may make it possible to minimize adverse events without compromising antiviral efficacy in most cases.     

Practical efficacy of sorafenib monotherapy for advanced hepatocellular carcinoma patients in a Hepatitis B virus-endemic area

Background  This study was conducted to assess the efficacy and safety of sorafenib monotherapy in clinical practice settings for Korean patients with hepatocellular carcinoma (HCC) related primarily to HBV infection. Methods  Medical records of 57 consecutive patients with unresectable or metastatic HCC treated with 400 mg bid sorafenib at the National Cancer Center, Korea between June 2007 and March 2008, were retrospectively reviewed. Results  The median patient age was 55 years (range, 28–76 years), and all patients had performance status 0–2 and Child–Pugh class A or B disease. HCC was etiologically related to HBV in 79.0% of patients. Eleven patients (19.3%) had modified UICC stage III tumors, 11 (19.3%) had stage IVa, and 35 (61.4%) had stage IVb. Following sorafenib monotherapy, 3 patients (5.3%) achieved a partial response and 18 (35.1%) achieved stable disease, with a disease control rate of 40.4%. The median times to progression (TTP) was 9.1 weeks (95% CI 3.4–14.8 weeks). Multivariate analyses showed that serum alpha-fetoprotein (α-FP) ≥400 ng/mL (HR, 2.810; P = 0.023) and the presence of massive intrahepatic tumors (HR, 7.633; P = 0.033) were independent predictors of shorter TTP. The most common grade 3/4 adverse events were hand-foot syndrome (8.8%), diarrhea (7.0%), and skin rash (7.0%). Exacerbation of underlying chronic hepatitis B was not found. Conclusion  Sorafenib monotherapy showed better outcomes with tolerable toxicity in Korean advanced HCC patients, who had intrahepatic nodular tumors and/or metastatic tumors, coupled with low levels of serum α-FP.     

Viro-immunologic response to ritonavir-boosted or unboosted atazanavir in a large cohort of multiply treated patients: the CARe Study

Currently, comparative data able to define the potency of boosted versus unboosted atazanavir in highly pretreated HIV-infected patients are limited. Specifically, in clinical practice it is very important to establish whether atazanavir-boosting with ritonavir warrants potency and efficacy that overcome the profile of unboosted drug. For this reason, our goal was to evaluate viro-immunologic determinants of response to atazanavir, in unboosted ATV400 or boosted ATV300/r formulation, from baseline to week 48 in highly pretreated HIV-infected patients enrolled in a prospective observational Italian study. Data from 354 patients included in an atazanavir "Early Access Program" (AI424-900) with baseline viremia 500 copies per milliliter or more and with an available virologic follow-up were examined using as-treated analysis. Of these, 200 (56.5%) and 154 (43.5%), respectively, received regimens containing ATV300/r or ATV400. Virologic success (VS) was defined as reaching viremia of less than 500 copies per milliliter during follow-up. Estimated median time to VS was 8 weeks in the ATV300/r group and 13 weeks in the ATV400 group. Proportion of patients achieving VS was higher in the ATV300/r group than in ATV400 group at week 12 (66% versus 47%), as well as at week 48 (86% versus 64%). At multivariate Cox regression, receiving ATV300/r dosing was independently associated with increased probability of achieving VS [adjusted hazard ratio (AHR): 1.57; 95% confidence interval (CI): 1.19-2.06]. Conversely, CDC stage C, higher baseline viral load, and more experience with protease inhibitors (PIs) were associated with poorer virologic response. In an unselected population of highly pretreated HIV-infected individuals, receiving atazanavir as part of antiretroviral regimen results in effective virologic response and immunologic recovery. The antiviral efficacy of atazanavir is greater when boosted with low-dose ritonavir.     

Improvement of Hemodialysis Catheter Function with Tenecteplase: A Phase III,Open-Label Study: TROPICS 4

Hemodialysis (HD) catheters are prone to thrombotic occlusion. We evaluated tenecteplase, a thrombolytic, for the treatment of dysfunctional HD catheters. Patients with tunneled HD catheters and blood flow rate (BFR) <300 mL/min received open-label tenecteplase (2 mg/lumen) for a 1 h intracatheter dwell. Treatment success was defined as BFR ≥300 mL/min and a ≥25 mL/min increase from baseline BFR, 30 min before and at the end of HD. Patients without treatment success at the end of the initial visit received another 2 mg dose of tenecteplase for an up to 72 h extended dwell. Of 223 enrolled patients, 34% (95% confidence interval [CI], 28–40%) had treatment success after a 1 h dwell. Mean (standard deviation [SD]) BFR change from baseline was 82 (124) mL/min. Treatment success in those who received extended-dwell tenecteplase (n = 116) was 49% (95% CI, 40–58%), with mean (SD) BFR change from baseline of 117 (140) mL/min. Reported targeted adverse events included five catheter-related bloodstream infections and one thrombosis. No intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications were reported. Tenecteplase administered as a 1 h or 1 h plus extended dwell was associated with improved HD catheter function in the TROPICS 4 trial.     

Mannose binding lectin levels are not related to radiographic damage in ankylosing spondylitis

In the current study we aimed to investigate the effect of MBL deficiency in radiographic damage of the spine in a large group of AS patients. One hundred and ninety-one AS patients and 85 healthy controls were studied. Disease activity, radiological scores, and demographic features were recorded. MBL levels were measured with standard ELISA kits. Results showed that median MBL levels in AS and healthy controls were 2,530 (range 0–5,861) ng/ml and 3,415 (0–7,950) ng/ml, respectively (p = 0.1). MBL deficiency (<500 ng/ml) was comparable in both groups (%21.5 in AS, % 17.6; p = 0.5). Disease activity, clinical picture, and therapies were not associated with MBL levels. Both BASRI and mSASSS scores were found similar in AS patients with or without MBL deficiency [BASRI: MBL < 500 ng/ml: 6(2–12), MBL ≥ 500 ng/ml: 6(2–12); p = 0.75], [mSASSS: MBL < 500 ng/ml: 3(0–72), MBL ≥ 500 ng/ml: 5(0–72); p = 0.81]. We conclude that MBL deficiency prevalence is not increased in AS patients and it is not a cause of a severe radiographic damage.     

Familial Mediterranean fever in the Iranian population: MEFV mutations in different ethnic groups

Background and aimsFamilial Mediterranean Fever (FMF) is an ethnically restricted genetic disease, found commonly among Mediterranean population, as well as Armenians, Turks, Arabs and Jews. The disease is caused by mutations in the MEFV gene, encoding the Pyrin protein. The aim of this study was to determine the mutation frequency in the clinically diagnosed FMF patients and the carrier rate among healthy first-degree relatives of patients from Iran.Methods59 patients (<17 years old) with clinical diagnosis of FMF in the absence of colchicine and 82 healthy family members, in three different ethnic groups were screened for the 5 most common MEFV mutations (M694V, M694I, M680I, V726A and E148Q).ResultsThe mean age of patients (27 females: 32 males) was 7.8 ± 3.23. Fever (94.9%) and abdominal pain (77.9%) was the most common clinical finding. Allele frequencies were different among different ethnic groups of Iranian population (p = 0.03). The most frequent mutation was M694V (29.6%) followed by M694I (8%), M680I (15%), V726A (16%) and E148Q (8%): homozygous (18.6%), compound heterozygous (52.5%) and simple heterozygous (16.9%). we could not detect any mutations in 16.95% of our patients. 9 (18%) healthy relatives were detected to have mutations of FMF.ConclusionsM694V was the most common MEFV mutation in various ethnic groups of Iranian patients.