Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial

From April 2003 to December 2006, 195 patients with de novo symptomatic myeloma and younger than 60 years of age were randomly assigned to receive either tandem transplantation up front (arm A, n = 97) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide (day + 90, 100 mg per day during 6 months) (arm B, n = 98). Patients included in arm B received a second transplant at disease progression. In both arms, autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m(2)) and granulocyte colony stimulating factor. Data were analyzed on an intent-to-treat basis. With a median follow-up of 33 months (range, 6-46 months), the 3-year overall survival was 65% in arm A and 85% in arm B (P = .04). The 3-year progression-free survival was 57% in arm A and 85% in arm B (P = .02). Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide (with second transplant in reserve for relapse or progression) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to tandem transplant in this setting. This study was registered at www.ClinicalTrials.gov as (NCT 00207805).     

Chemical characterization,cytotoxic, antioxidant,antimicrobial, and enzyme inhibitory effects of different extracts from one sage (Salvia ceratophylla L.) from Turkey: open a new window on industrial purposes

In the present study, the methanolic, hydro-methanolic, dichloromethane, hexane and aqueous extracts of Salvia ceratophylla L. (Family: Lamiaceae), a lemon-scented herb, were tested for total phenolic (TPC) and flavonoid content (TFC) and antioxidant activities were evaluated using a battery of assays (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity, total antioxidant capacity (TAC) (phosphomolybdenum) and metal chelating). Enzyme inhibitory effects were investigated using acetyl- (AChE), butyryl-cholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase as target enzymes. Regarding the cytotoxic abilities, HepG2, B164A5 and S17 cell lines were used. The phytochemical profile was conducted using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Our data showed that the methanolic aerial extracts possessed the highest phenolic (72.50 ± 0.63 mg gallic acid equivalent per g) and flavonoid (43.77 ± 1.09 mg rutin equivalent per g) contents. The hydro-methanolic aerial extract showed significant DPPH radical scavenging activity (193.40 ± 0.27 mg TE per g) and the highest reducing potential against CUPRAC (377.93 ± 2.38 mg TE per g). The best tyrosinase activity was observed with dichloromethane root extract (125.45 ± 1.41 mg kojic acid equivalent per g). Among the tested extracts, hexane root extract exerted the highest antimicrobial potential with a minimum inhibitory concentration value of 0.048 mg mL⁻¹. Methanolic root extract showed the lowest cytotoxicity (28%) against HepG2 cells. Phytochemical analysis revealed the presence of important polyphenolic compounds including luteolin, gallic acid, rosmarinic acid, to name a few. This research can be used as one methodological starting point for further investigations on this lemon-scented herb.

Our findings suggested that Salvia ceratophylla could be one potential raw material in industrial applications.     

Biological Transformation of Zearalenone by Some Bacterial Isolates Associated with Ruminant and Food Samples

Zearalenone (ZEA) is a secondary metabolite produced by Fusarium spp., the filamentous fungi. Food and feed contamination with zearalenone has adverse effects on health and economy. ZEA degradation through microorganisms is providing a promising preventive measure. The current study includes isolation of 47 bacterial strains from 100 different food and rumen samples. Seventeen isolates showed maximum activity of ZEA reduction. A bacterial isolate, RS-5, reduced ZEA concentration up to 78.3% through ELISA analysis and 74.3% as determined through HPLC. Ten of the most efficient strains were further selected for comparison of their biodegradation activity in different conditions such as incubation period, and different growth media. The samples were analyzed after 24 h, 48 h, and 72 h of incubation. De Man Rogosa Sharp (MRS) broth, Tryptic soy broth, and nutrient broth were used as different carbon sources for comparison of activity through ELISA. The mean degradation % ± SD through ELISA and HPLC were 70.77% ± 3.935 and 69.11% ± 2.768, respectively. Optimum reducing activity was detected at 72 h of incubation, and MRS broth is a suitable medium. Phylogenetic analysis based on 16S rRNA gene nucleotide sequences confirmed that one of the bacterial isolate RS-5 bacterial isolates with higher mycotoxin degradation is identified as Bacillus subtilis isolated from rumen sample. B05 (FSL-8) bacterial isolate of yogurt belongs to the genus Lactobacillus with 99.66% similarity with Lactobacillus delbrukii. Similarly, three other bacterial isolates, D05, H05 and F04 (FS-17, FSL-2 and FS-20), were found to be the sub-species/strains Pseudomonas gessardii of genus Pseudomonas based on their similarity level of (99.2%, 96% and 96.88%) and positioning in the phylogenetic tree. Promising detoxification results were revealed through GC-MS analysis of RS-5 and FSL-8 activity.     

The effects of the attributable fraction and the duration of symptoms on burden estimates of influenza‐associated respiratory illnesses in a high HIV prevalence setting,South Africa, 2013‐2015

Background

The attributable fraction of influenza virus detection to illness (INF‐AF) and the duration of symptoms as a surveillance inclusion criterion could potentially have substantial effects on influenza disease burden estimates.

Methods

We estimated rates of influenza‐associated influenza‐like illness (ILI) and severe acute (SARI‐10) or chronic (SCRI‐10) respiratory illness (using a symptom duration cutoff of ≤10 days) among HIV‐infected and HIV‐uninfected patients attending 3 hospitals and 2 affiliated clinics in South Africa during 2013‐2015. We calculated the unadjusted and INF‐AF‐adjusted rates and relative risk (RR) due to HIV infection. Rates were expressed per 100 000 population.

Results

The estimated mean annual unadjusted rates of influenza‐associated illness were 1467.7, 50.3, and 27.4 among patients with ILI, SARI‐10, and SCRI‐10, respectively. After adjusting for the INF‐AF, the percent reduction in the estimated rates was 8.9% (rate: 1336.9), 11.0% (rate: 44.8), and 16.3% (rate: 22.9) among patients with ILI, SARI‐10, and SCRI‐10, respectively. HIV‐infected compared to HIV‐uninfected individuals experienced a 2.3 (95% CI: 2.2‐2.4)‐, 9.7 (95% CI: 8.0‐11.8)‐, and 10.0 (95% CI: 7.9‐12.7)‐fold increased risk of influenza‐associated illness among patients with ILI, SARI‐10, and SCRI‐10, respectively. Overall 34% of the estimated influenza‐associated hospitalizations had symptom duration of >10 days; 8% and 44% among individuals aged <5 and ≥5 years, respectively.

Conclusion

The marginal differences between unadjusted and INF‐AF‐adjusted rates are unlikely to affect policies on prioritization of interventions. HIV‐infected individuals experienced an increased risk of influenza‐associated illness and may benefit more from annual influenza immunization. The use of a symptom duration cutoff of ≤10 days may underestimate influenza‐associated disease burden, especially in older individuals.     

Minimally differentiated acute myeloid leukemia (FAB AML-M0): prognostic factors and treatment effects on survival--a retrospective study of 42 adult cases

Data from 42 adult patients with newly diagnosed minimally differentiated (M0) acute myeloid leukemia (AML) were reported. Clinical and biological characteristics at diagnosis were heterogenous. All patients received induction chemotherapy combining an anthracycline with cytarabine. Complete remission (CR) was achieved in 22 cases (52%). Most patients received continuation chemotherapy. Median disease-free survival (DFS) was 13.6 months with a 2-year survival rate of 28%. As post-remission therapy, 7 patients could be allografted and showed an encouraging outcome. Overall, 14 patients have relapsed (63%) after a median time of 10.2 months. Median overall survival (OS) was 20.5 months with a 5-year survival rate of 18%. This retrospective analysis points to a somewhat heterogenous group of AML in terms of biological features and outcome, and warrants a larger multicenter study with study in molecular biology to clarify treatment effects further.     

Clinical and sonographic diagnosis of occiput posterior position: a prospective study of 350 deliveries

OBJECTIVE: To evaluate clinical reliability compared to intrapartum ultrasound as a tool to diagnose occiput posterior position and to investigate the proportion of rotations occurring during labour. PATIENTS AND METHODS: 350 women in labor with a singleton fetus in a vertex position were prospectively studied using ultrasound and obstetrical examination. Outcome of labor was also monitored. RESULTS: Reliability of clinical examination is 85,7%, initial occiput posterior position represented 40,2% and most rotated in an anterior position (84, 8%) while only 0,6% of initial anterior positions delivered in occiput posterior position. Logistic regression did not allow to find significant predictor of occiput posterior position rotation. DISCUSSION AND CONCLUSION: Clinical examination is relatively reliable for posterior position diagnosis and in most cases, initially occipitoposterior positions rotate anteriorly.     

Molecular cytogenetic study of derivative chromosome 9 deletion in chronic myeloid leukemia patients

The aims of this study are to investigate the frequency of derivative chromosome 9 (der (9)) deletion in Tunisian patients with chronic myeloid leukemia (CML) and to assess the correlation between this deletion and the cytogenetic response for patients treated with hydroxyurea (HU) or imatinib (IM). Karyotype analysis of 336 patients with CML was performed with R-banding technique. Fluorescence in situ hybridization (FISH) was carried using home-brew probes 17L7 and 248J22 for detecting, respectively, adjacent 5??ABL and 3??BCR deletions on der(9). Cytogenetic study demonstrated typical t(9;22)(q34;q11) translocation in 89.6% and variant translocation in 10.4% of patients. Interphase FISH studies showed deletion of der(9) in 59 (17.6%) of the 336 patients, 23 (39%) of them had variant rearrangements. There are 19 patients with solely 5??ABL deletion and 40 with concomitant 5??ABL and 3??BCR deletions. Cytogenetic response was evaluated during 18?months with HU or IM therapy. Our results demonstrate that (a) 3??BCR deletion is associated with 5??ABL deletion in all patients with der(9) deletions, (b) the 5??ABL and 3??BCR deletions arise simultaneously with t(9;22), (c) deletions on der(9) chromosome were frequently encountered in older patients and in patients presenting variant rearrangements, (d) both 5??ABL and 3??BCR deletions were associated with cytogenetic response failure in patients treated with HU, however, patients treated with IM and carrying der(9) deletions presented better cytogenetic response.