Gemox-Vinorelbine as Pre-Transplant Salvage in Diffuse Large B Cell Non-Hodgkin Lymphoma Patients Single Institutional Prospective Phase II Study

Background: Salvage chemoimmunotherapy is given to determine the chemosensitivity of relapsed/refractory disease and to reduce the burden of disease prior to transplantation. There is no consensus regarding an optimal salvage regimen for all transplant-eligible patients, and the preferred approach varies by institution and clinician. Salvage chemoimmunotherapy comprises a combination of relatively high doses of non-cross-resistant drugs together with a monoclonal antibody against CD20 (eg, rituximab) and there is a trend towards selecting salvage regimen based on pathologic features of disease either germinal center DLBCL or Activated B-cell (ABC) DLBCL. Gemcitabine/oxaliplatin (GemOx), with or without rituximab, is a frequently used treatment of relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL), and is NCCN -listed for transplant-eligible patients. Vinorelbine (vinca alkaloid) is a mitotic inhibitor which has shown encouraging early results in the treatment of heavily pre-treated relapsed or refractory lymphoma. In this study we explored the value of addition of vinorelbine(navelbine) to GemOx regimen in inducing more Complete remission (CR) in relapsed or refractory non-Hodgkin lymphoma.Aim: we investigated the efficacy and safety of Gemox-vinorelbine protocol as a pre-transplantation regimen in refractory and relapsed non Hodgkin lymphoma diffuse large B-cell type either Germinal Center B-cell or activated (ABC) B-cell type. Methods: Treatment consists of gemcitabine at 600mg /m2 on days 1 and 2, oxaliplatin 60 mg/m2 on days 1 and 2, vinorelbine 20mg/m2 d1 and dexamethasone 16mg/m2 d1-d4 repeated every 2 weeks d1, d15 with addition of Rituximab (375mg/m2) according to institute policy. Eligible patients were relapsed/refractory (R/R) NHL. Patients were recruited from Oncology Center Mansoura University during the period between December 2020 and September 2022 with a minimum follow of 6 months. Assessment was performed after 2-4 cycles of treatment by PET-CT. Results: Forty-five eligible patients (31 males ,69%) were treated with Gemox-vinorelbine ,the median number of treatment cycles was 3 (1-6).At the 1st re-evalution (after 2-4 cycles),forty one patients were eligible for treatment evalution,12 patients achieved complete remission(29.2%) , 10 patients achieved partial response(24.4%) , 3 patients had stable disease(7.3%) and 16 patients had progressive disease (39%).Patients who had partial response completed 2 more cycles (10 patients) ,4 of them achieved CR at 2nd re-evaluation (after 6 cycles) and 6 had a progressive disease .At least 3 cycles are needed for CR. A total of 16 patients achieved CR (39%). Eleven Patients proceeded to ASCT and 5 patients were rejected for bone marrow transplantation for causes like antithrombin III deficiency, one relapsed after stem cell collection, one considered to be in CR1 by bone marrow transplantation team. Gemox-vinorelbine protocol didn’t affect Stem Cell harvesting nor engraftment. Any Grade toxicities were thrombocytopenia (66.6%), anemia (35.5%), neutropenia (33.3%), febrile neutropenia (15.5%) Neuropathy (33.3%), mucositis (20%). Treatment related mortality occurred in one patient (NF progressed to septic shock).The median progression free survival (PFS) was 10.8 months and median OS was 12 months. Both PFS nor OS was affected by cell of origin of DLBCL either germinal Center (GC) or non-germinal center (non-GC). Significant predictors for OS were IPI, late relapse >12 months versus primary refractory and early relapse <12months and number of prior lines. Summary and conclusions: Gemox-vinorelbine had good activity as as a salvage regimen in R/R NHL(DLBCL) especially if used as 1st salvage in transplantation candidate patients

STUDY THE POTENTIAL ANTIOXIDANT EFFECT OF VITAMIN D3 SUPPLEMENTATION ON THE LEVEL OF EXTRACELLULAR SUPEROXIDE DISMUTASE IN ASTHMATIC PATIENTS

Objective: This study was designed to evaluate the potential antioxidant effect of vitamin D3 supplementation in chronic asthma patients.Methods: A total of 44 candidate patients were diagnosed with asthma allocated as Group 1 includes 20 patients assigned to receive conventional therapy for asthma and Group 2 includes 24 patients assigned to receive conventional therapy for asthma plus 2000 IU vitamin D3 tablet for 3-month period. Furthermore, 30 apparently healthy subjects were included in the study as a control group. Pulmonary function test, serum 25-hydroxy vitamin D levels, serum extracellular superoxide dismutase (SOD3) levels were measured before and after 3 months therapy.Results: The mean forced expiratory volume in 1 second (FEV1) both the measured and the percentage of predicted value showed a highly significant increase after 3 months treatment compared to pre-treatment value in both study groups (p<0.01). When compared to pre-treatment value, there was no significant increase in forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC) in Group 1 (p>0.05), nevertheless, Group 2 showed highly significant increase after 3 months (p<0.01). Approximately, 90-96% of adult asthmatic patients revealed vitamin D deficiency (<20 ng/ml). Post-treatment with adjuvant vitamin D3 therapy, 25% of patients obtained acceptable level of vitamin D sufficiency (≥30 ng/ml). After 3 months of the treatment, Group 1 patients showed a significant decrease in mean SOD3 level compared to pre-treatment level (p<0.05), while Group 2 patients showed a significant increase in mean SOD3 level compared to pre-treatment level (p<0.05).Conclusion: Most of the asthmatic patients revealed vitamin D deficiency and supplementation with vitamin D3 reduce oxidative stress burden in those patients

The Effect of Curcumin Adjuvant Therapy on Pulmonary Function and Levels of Interleukin-6 (IL-6) and Superoxide Dismutase-3 (EC-SOD3) in Patients with Chronic Bronchial Asthma

This study was designed to evaluate the effectiveness of curcumin supplement as antioxidant and anti-inflammatory in patients with chronic bronchial asthma. Forty patients diagnosed with chronic bronchial asthma were enrolled in this study and allocated into group (1) patients   assigned to receive conventional therapy of asthma, and group (2) patient assigned to receive conventional therapy of asthma combined with 750 mg curcumin supplement twice daily for two months. Pulmonary function test, asthma control test, serum interleukin-6 and serum extracellular super oxide dismutase 3 were measured before and after two months in both study groups. After two months, the mean values of pulmonary function test (spirometry) and asthma control score showed significant increase compared to pre-treatment values in group 2 patients (P<0.01). Moreover, there was marked decrease in the level of interleukin-6 in group 2 patients after two months (p< 0.05) compared to the increased in group 1 patients. The mean level of super oxide dismutase 3 didn’t show any increase in both study groups after treatment. Curcumin supplement produced improvement in pulmonary function of patients with chronic bronchial asthma along with the reduction in inflammatory status. No change in endogenous oxidative status after curcumin supplementation

Combined cosine-linear regression model similarity with application to handwritten word spotting

The similarity or the distance measure have been used widely to calculate the similarity or dissimilarity between vector sequences, where the document images similarity is known as the domain that dealing with image information and both similarity/distance has been an important role for matching and pattern recognition. There are several types of similarity measure, we cover in this paper the survey of various distance measures used in the images matching and we explain the limitations associated with the existing distances. Then, we introduce the concept of the floating distance which describes the variation of the threshold’s selection for each word in decision making process, based on a combination of Linear Regression and cosine distance. Experiments are carried out on a handwritten Arabic image documents of Gallica library. These experiments show that the proposed floating distance outperforms the traditional distance in word spotting system

Fungal metabolites in human health and diseases—an overview

Fungi produce a wide range of secondary metabolites. Some of these metabolites are toxic to humans and cause various health disorders, ranging from acute poisoning to chronic diseases. Contrary to this, some fungal metabolites are valuable sources in therapeutics, such as penicillin. Herein, researchers briefly highlight the role played by different fungal metabolites in human health and diseases and give an overview of the most common fungal genera

Assessment of leukemia inhibitory factor and glycoprotein 130 expression in endometrium and uterine flushing: a possible diagnostic tool for impaired fertility

Abstract Background Uterine receptivity and implantation are complex processes requiring coordinated expression of molecules by zygote and uterus. Our objective was to evaluate the role of the endometrial expression of leukemia inhibitory factor (LIF) and its glycoprotein 130 (gp130) receptor molecules and their secretion in uterine flushing during the window of implantation in cases of primary unexplained infertility Case presentation The study was conducted on 25 infertile women with unexplained infertility for at least two years and 10 normal fertile women as a control group . Endometrial tissue and uterine flushing were obtained. Each tissue specimen was divided into two pieces; one piece was used for histological dating of the endometrium and for immunostaining of progesterone receptors, and the second was used for RNA extraction and PCR assay of LIF and gp130 mRNA expression. Serum estrogen and progesterone were measured for all subjects. LIF mRNA was expressed in the endometrium of all normal fertile women but significantly decreased in infertile women. LIF was not detectable in 88% of infertile women while it was fairly detectable in 12% of them. Gp130 mRNA was hardly detectable in both fertile and infertile women with no difference between them. Infertile women secreted significantly less LIF and gp130 molecules in the uterine flushing compared with normal fertile women. Conclusions Expression of LIF mRNA in endometrium could be used as a molecular marker of unexplained infertility. Assessment of secreted LIF and gp130 molecules in uterine flushing could be another useful and safe method for predicting successful implantation as well as for diagnosing and eventually treating women with impaired fertility using recombinant human LIF. </jats:sec

Diet composition and feeding habits of the milk shark Rhizoprionodon acutus (Rüppell, 1837) in the Gulf of Suez, Red Sea

This study is aimed to provide detailed information on the diet of Rhizoprionodon acutus in the Gulf of Suez. The findings suggest the specialized feeding behavior of this species in the Gulf of Suez. A total of 240 Stomachs of R. acutus were examined. The number of stomachs that contained prey items was 146 (60.83%), while 94 stomachs were empty (39.16%). Identifiable prey items belonging to 24 species of marine organisms correspond to 13 families of teleost fishes, three families of cephalopods, two families of crustaceans, one of eels, and one of sea urchins. Prey items of little importance included the teleost fishes Lutjanus bohar (0.003% (and the sea urchin Clypeaster humilis, (0.004%); each was only found in one stomach. Unidentified teleosts comprised the bulk of the observed prey items in terms of frequency of occurrence (63.7%), number (66.67%), weight (53.94%), and relative importance (96.54%). The identified prey items contained pelagic, demersal, reef-associated, and benthic organisms. When grouping food items into their large categories and comparing them in terms of %IRI, teleost fishes were the preferable prey item, with 96.54% unidentified and 1.49% identified, followed by Cephalopods (1.73%), eels (0.16%) and finally, Crustacean (0.09%). The trophic level of R. acutus in the Gulf of Suez was estimated to be 4.2, which categorizes it as a tertiary consumer

Brain-derived neurotrophic factor in asthmatic children

Background: Brain-derived neurotrophic factor (BDNF) regulates the cross-talk between the immune and nervous systems which may play an important role in asthma pathophysiology. Objective: This study was aimed to investigate the relation between BDNF and asthma exacerbation and severity, and to study its possible correlation to eosinophilic counts in blood and sputum. Methods: Twenty-seven asthmatic children were studied during both exacerbation and remission. According to acute exacerbation severity as assessed clinically and by peak expiratory flow rate (PEFR), they were equally subdivided into 3 groups (mild, moderate and severe). Serum and sputum BDNF levels as well as blood and sputum eosinophilic counts were estimated in all patients in comparison to 30 healthy children with no personal or family history of atopy. Results: BDNF levels (in serum and sputum) and eosinophilic counts (in blood and sputum) were significantly elevated in asthmatic patients, whether studied as one group or subgrouped into mild, moderate and severe as compared to controls. Patients with mild, moderate and severe acute asthma exacerbation had significantly higher values of BDNF (in serum and sputum) and eosinophilic count (in blood and sputum) than the corresponding values measured during remission. The latter values were still higher than those of the control group. BDNF in serum and sputum indirectly correlated with asthma severity as evidenced by their negative correlation with PEFR. However, sputum BDNF correlated better with the severity of asthma exacerbation as evidenced directly by its significant increase with clinical severity. Both serum and sputum BDNF levels revealed significant positive correlations with eosinophilic count in blood and sputum among all studied groups. Conclusion: BDNF probably plays a role in the evolution of asthma exacerbation and it reflects the degree of asthma severity during exacerbation. It might also represent an objective indicator of remission and treatment efficacy. Studies with specific BDNF receptor antagonists or synthesis inhibitors are required as BDNF may prove to be a reasonable target for a new therapy in future.Keywords: BDNF, neurotrophins, bronchial asthma, asthma severity, neurogenic inflammationEgypt J Pediatr Allergy Immunol 2003; 1(2): 102-

Antinucleosome antibodies as early predictors of lupus nephritis

Background: The role of the nucleosome in the induction of antibody response in lupus mediated tissue damage especially glomerulonephritis, may provide a new insight in the early diagnosis and alternative therapeutic developments in systemic lupus erythematosus (SLE). Objectives: To evaluate the frequency and specificity of antinucleosome antibody expression in SLE patients in relation to disease activity. Also, to assess their predictive value in subclinical lupus nephritis. Methods: This study included 26 patients with SLE and 52 control subjects (26 were healthy and 26 had juvenile rheumatoid arthritis "JRA"). Among lupus patients, 15 had clinical evidence of renal involvement. After clinical evaluation to calculate the SLE disease activity index (SLEDAI), measurements of urinary microalbumin and serum antinucleosome antibodies (antinucleosome specific, antihistone and anti ds-DNA antibodies by ELISA) were performed. Patients without clinical evidence of renal involvement were followed up for one year and measurement of urinary microalbumin was repeated at the end of the study period. Those who later developed microalbuminurea were categorized as patients with subclinical lupus nephritis. Results: The expression of the 3 studied antinucleosome antibodies was significantly higher among lupus patients as compared to JRA patients and healthy controls. Seropositivity for one or more antinucleosome antibodies was elicited in 84.5% of lupus patients. Serum levels of the 3 antinucleosome antibodies were significantly higher among lupus patients with clinical nephritis than those without nephritis. ANSAb had higher sensitivity, specificity and positive and negative predictive values for subclinical lupus nephritis (100%) than antihistone and anti ds-DNA antibodies (43%, 100%, 100% and 50% respectively for either antibodies). All patients with lupus nephritis were seropositive for at least one of the antinucleosome antibodies, while those without clinical or subclinical nephritis were seronegative for the 3 antinucleosome antibodies. In 27.3% of patients with lupus nephritis, ANSAB was positive while both antihistone and ds-DNA antibodies were negative. Antinucleosome antibodies correlated positively with SLEDAI and cumulative steroid dose and negatively with corrected creatinine clearance. Conclusions: The observed sensitivity and specificity of antinucleosome specific antibodies as early indicators of subclinical lupus nephritis appear encouraging and deserve further analysis on a large scale in order to confirm their validity, especially in the anti ds-DNA seronegative lupus patients.Keywords: antinucleosome antibodies, antinucleosome specific antibodies, anti ds-DNA antibodies, antihistone antibodies, SLE, lupus nephritisEgypt J Pediatr Allergy Immunol 2005; 3(2):54-6