Combined impact of COVID-19 and renal failure on taste perception in a sample of the Egyptian population.

PURPOSE: The present study aims to investigate the prevalence and severity of taste impairment among post-coronavirus disease 2019 (COVID-19) hemodialysis patients in a sample of the Egyptian population. METHODS: This study was conducted on 272 post-COVID-19 subjects, of whom 136 were hemodialysis patients and 136 were healthy controls. History taking, clinical examination, and assessment of altered taste score, tongue coating index, salivary flow rate, and salivary pH were performed. RESULTS: The present study revealed a high prevalence of impaired taste function in post-COVID-19 hemodialysis patients with 72.06% affected in varying degrees; mild (25%), moderate (3.68%), severe (30.15%), and overwhelming taste impairment (13.24%). However, only 12.5% of the control group reported just a mild degree of taste impairment. CONCLUSION: The current study has shown the high prevalence and severity of taste impairment in post-COVID-19 end-stage renal disease (ESRD) patients on hemodialysis (72.06%), which indicates the combined deteriorating effect of both COVID-19 and renal failure on taste function emphasizing the importance of prompt identification and management of COVID-19 associated taste impairment to improve the quality of life in hemodialysis patients.

Corrigendum: Performance evaluation of Moringa oleifera seeds aqueous extract for removing Microcystis aeruginosa and microcystins from municipal treated-water.

[This corrects the article DOI: 10.3389/fbioe.2023.1329431.].

Epidemiology of Sjogren's syndrome in a sample of the Egyptian population: a cross-sectional study.

OBJECTIVE: To investigate the prevalence of Sjögren's syndrome (SS) and the associated factors in a sample of the Egyptian population. METHODS: This cross-sectional study obtained data by screening subjects from several hospitals in different governorates across Egypt. Demographic and health data were collected including symptoms and type of Sjögren's syndrome, associated autoimmune diseases, the presence of specific autoantibodies and associated malignancies. RESULTS: The study analysed 7960 participants and 64 (0.80%) had SS. Of these, 22 (34.38%) had primary SS and 42 patients (65.63%) had secondary SS. For the total study cohort, the prevalence of primary and secondary SS was 0.28% and 0.53%, respectively. There was a higher prevalence of SS in females compared with males and SS was more common in the fifth and sixth decades. All patients with SS complained of oral and ocular dryness. The most common concomitant autoimmune disease was rheumatoid arthritis. Anti-SSA (Ro) and anti-SSB (La) antibodies were the most frequently associated autoantibodies. Only two patients had non-Hodgkin's lymphoma. CONCLUSION: This was the first study to describe the prevalence of SS in Egypt. SS is not a rare disease in Egypt, so raising awareness of SS in both patients and healthcare professionals is very important.

Effectiveness of thyme honey in the management of xerostomia in geriatric patients with end-stage renal disease: a randomized controlled clinical trial with a biochemical assessment.

BACKGROUND: Taking into consideration the value of the oral health condition in geriatric people with end-stage renal disease (ESRD) associated with xerostomia and believing that salivary stimulants or substitutes could potentially be used to manage this condition. This study aimed to evaluate the clinical effectiveness of thyme honey as oral rinse in geriatric patients with ESRD using the subjective dry mouth score as a primary objective and to assess the effect of thyme honey on the salivary nitric oxide level, salivary flow rate, and salivary ph in addition to objective dry mouth score as a secondary objective. METHODS: This was a single blinded randomized controlled trial with two equal arms, the interventional arm (thyme honey oral rinse) and the control arm (saline). Twenty-eight geriatric patients with ESRD undergoing hemodialysis complained of xerostomia were recruited from the renal dialysis center. Patients in both arms followed the same administration protocol either with thyme honey oral rinse or saline. The following clinical parameters (the subjective and objective dry mouth scores, salivary flow rate, salivary ph, and salivary nitric oxide (NO) levels) were evaluated for both groups at different intervals (baseline, 1 week, and 1 month). RESULTS: In the current study, it was found that both the subjective and objective dry mouth scores were significantly lower after one month of using thyme honey oral rinse (1.86 ± 0.66B) and (2.21 ± 0.43B) respectively, than the control group (3.07 ± 0.73B) and (3.07 ± 0.83B), respectively with a (p < 0.001). Also, the salivary flow rate was significantly higher after one month of using thyme honey oral rinse (1.56 ± 0.51A), than the control group (0.78 ± 0.27A) with a (p < 0.001). For the NO levels, there was a significant increase in measured value after 1 month in the intervention group (p < 0.001), while for the control group the change was not statistically significant (p = 0.166). CONCLUSIONS: The results of the current study have revealed the efficacy of Thyme honey oral rinse in the management of xerostomia in geriatric patients with ESRD. Trial registration The ClinicalTrials.gov Identifier for this study is NCT05247008.

Long-term outcomes of percutaneous closure of ventricular septal defects in children using different devices: A single centre experience from Egypt.

BACKGROUND: The feasibility of percutaneous closure ventricular septal defects (VSD) in children has been previously proven. However, data on long-term outcomes are limited. We aim to evaluate the long-term outcome of our experience with percutaneous closure of VSD using various occluders. METHODS: Retrospective institutional analysis of children who underwent transcatheter closure of perimembranous and muscular VSDs between September 2012 and February 2020. Patient demographics, procedural, and long-term follow-up data were comprehensively analyzed. Patients who lost to follow-up within two years post-procedure were excluded. RESULTS: We identified 75 patients (54.7% males) with a median of 66 months (IQR, 46-96). The closure success rate at one year was 95.7%. Complete heart block was detected in two patients early post-procedure and resolved with steroids. The VSDs were perimembranous (52%), muscular (33.33%), and residual (14.67%). Implanted devices were Pfm Nit-Occlud LeˆVSD Coil (42.7%), HyperionTM VSD Muscular Occluder (28%), Amplatzer VSD muscular occluder (10.7%), Amplatzer Duct Occluder (14.7%), Occlutech Muscular VSD Occluder (2.7%), and Amplatzer Duct Occluder II (1.3%). No new arrhythmia or valve regurgitation was detected after two years post-procedure. Persisted complications on long-term follow-up included: residual shunting in 3(4%), mild tricuspid regurgitation in 2(2.7%), and aortic regurgitation in 2(2.7%), with one immediate post-catheterization mild aortic regurgitation worsened during follow-up, requiring surgical repair of VSD three years after device implantation. No deaths were reported. CONCLUSION: Long-term outcomes of pediatric transcatheter VSD closure using different devices are satisfactory. Post-procedural adverse events are limited, but long-term surveillance is necessary to monitor their progression.

Endoscopic ultrasound-guided hepaticogastrostomy by puncturing both B2 and B3: a single center experience.

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) through ducts B2 or B3 is effective in most patients with biliary obstruction, because B2 and B3 commonly join together. However, in some patients, B2 and B3 do not join each other due to invasive hilar tumors; therefore, single-route drainage is insufficient. Here, we investigated the feasibility and efficacy of EUS-HGS through both B2 and B3 simultaneously in seven patients. We decided to perform EUS-HGS through both B2 and B3 to achieve adequate biliary drainage because these two ducts were separate from each other. Here, we report a 100% technical and overall clinical success rate. Early adverse effects were closely monitored. Minimal bleeding was reported in one patient (1/7) and mild peritonitis in one patient (1/7). None of the patients experienced stent dysfunction, fever, or bile leakage after the procedure. EUS-HGS through both B2 and B3 simultaneously is safe, feasible, and effective for biliary drainage in patients with separated ducts.

Oral Changes in Hospitalized COVID-19 Patients: A Cross-Sectional Multicentric Study.

Background: Coronavirus disease 2019 (COVID-19) has rapidly spread over the globe, and several oral symptoms have been documented. However, it is unclear whether these lesions are the result of coronavirus infection or are secondary symptoms of the patient's systemic illness. The aim of this study was to collect data from various hospitals on COVID-19 patients with oral involvement in order to highlight different oral changes that may be manifested in those patients. Methods: This observational cross-sectional multicenter study used an online questionnaire covering oral signs and symptoms that were believed to be related to COVID-19 patients who were hospitalized in different hospitals in Egypt. Results: 94.3% of the 210 patients who participated in the current study developed oral symptoms. Altered taste sensation (56.2%), burning sensation (43.3%), and oral candidiasis (40%) were the most prevalent oral symptoms (34.4%) that were found in the studied sample. Conclusions: COVID-19 has a major influence on the oral cavity, with numerous oral symptoms that may impair quality of life. Thus, considering the need for support, pain control, and management for a better prognosis, the clinical dental evaluation of hospitalized patients with infectious diseases like COVID-19 should be addressed.

Utility of forward-view endoscopic ultrasound in fine-needle aspiration in patients with a surgically altered upper gastrointestinal anatomy.

BACKGROUND/AIMS: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) using oblique-view EUS in patients with a surgically altered anatomy (SAA) of the upper gastrointestinal tract is limited because of difficult scope insertion due to the disturbed anatomy. This study aimed to investigate the efficiency of forward-view (FV)-EUS in performing FNA in patients with a SAA. METHODS: We retrospectively investigated 32 patients with a SAA of the upper gastrointestinal tract who visited Aichi Cancer Center Hospital in Nagoya, Japan, between January 2014 and December 2020. We performed-upper gastrointestinal EUS-FNA using FV-EUS combined with fluoroscopic imaging to confirm tumor recurrence or to make a decision before chemotherapy or after a failure of diagnosis by radiology. RESULTS: We successfully performed EUS-FNA in all studied patients (100% technical success), with the specificity, sensitivity, and accuracy of 100%, 87.5%, and 87.8%, respectively, with no complications. CONCLUSION: EUS-FNA using FV-EUS combined with fluoroscopic imaging is an effective and safe technique for tissue acquisition in patients with a SAA.

Performance evaluation of Moringa oleifera seeds aqueous extract for removing Microcystis aeruginosa and microcystins from municipal treated-water.

Introduction: Toxic microcystins (MCs) produced by cyanoprokaryotes -particularly by the cosmopolitan cyanobacterium Microcystis aeruginosa- pose adverse effects on aquatic organisms and their ecosystem and may also cause serious impacts on human health. These harmful monocyclic heptapeptides are the most prevalent cyanotoxins reported in freshwaters and must be eliminated for avoiding MCs release in receiving water bodies. Hence, this work aimed to test the efficacy of Moringa oleifera seeds water-based extract (MO) as a natural coagulant for removing cyanobacteria (especially M. aeruginosa), microalgae, and its associated MCs from pre-treated municipal wastewaters. Methodology: Four different MO coagulant doses (25, 50, 75 and 100 mg L-1) were investigated for cyanobacteria and microalgae removal by conventional coagulation assays and morphology-based taxonomy studies. Additionally, water turbidity and chlorophyll a (Chl a) content were also determined. Further, the presence and concentration of MCs soluble in water, remaining in the particulate fraction, and flocculated within the residual sludge were assessed using high-performance liquid chromatography coupled with diode array detection (HPLC-DAD). Results: The treatment with MO at 100 mg L-1 substantially reduced the number of cyanobacterial and microalgal species in the treated samples (average removal rate of 93.8% and 86.9%, respectively). These results agreed with a ∼44% concomitant reduction in Chl a and ∼97% reduction in water turbidity (a surrogate marker for suspended solids content). Notably, MCs concentrations in the treated water were significantly lowered to 0.6 ± 0.1 µg L-1 after addition of 100 mg L-1 MO. This value is below the WHO recommended limits for MCs presence in drinking water (<1.0 µg L-1). Discussion: The present study provides promising insights into the applicability of MO as a cost-effective, reliable, and sustainable natural coagulant, particularly for using in developing countries, to eliminate harmful cyanobacteria and cyanotoxins in municipal water treatment facilities.

Molecular Study of Accessory-Gene-Regulator in Staphylococcus aureus Isolated from Sepsis in Pediatric Patients.

BACKGROUND: Pediatric sepsis due to Staphylococcus aureus (S. aureus) is associated with high morbidity and mortality. Accessory-Gene-Regulator (agr) has a role in the pathogenesis of S. aureus through controlling and regulating the expression of virulence genes. Therefore, the aim of the present study was to investigate the prevalence of genotypes of the agr system in S. aureus isolated from children with sepsis and to assess their relationship to biofilm formation and antibiotic resistance. METHODS: The study was a retrograde cross-sectional study that included 131 children with health care associated sepsis due to S. aureus. The isolated S. aureus was investigated for their ability to form biofilm by microplate method, antibiotic susceptibility pattern by disc diffusion method, and molecular determination of agr genotypes by polymerase chain reaction (PCR). RESULTS: Methicillin resistant S. aureus (MRSA) was defined by resistance to cefoxitin antibiotic disc in 70 (53.4%) of the isolates and biofilm formation was positive in 67 (58%) of the isolates. Molecular study of the agr genes revealed that 54 (41.2%), 40 (30.5%), 27 (20.6%), and 10 (7.5%) of the studied isolates had agr I, agr II, agr III, and agr IV, respectively. In comparison between MRSA and methicillin sensitive S. aureus (MSSA), there was a signif-icant increase in biofilm formation among MRSA (65.7%, p = 0.01) compared to MSSA (34.3%) and an increase in agr genotype I among MRSA (68.6%, p = 0.001) compared to agr I in MSSA (9.8%). There was a significant association with the presence of a central venous catheter (51.4%, p = 0.001) and urinary tract catheter (81.4%, p = 0.001) in children with MRSA compared to children with MSSA (21.3%, OR = 3.9, 95% CI = 1.8 - 8.5 and 36.1%, OR = 7.8, 95% CI 3.5 - 17.3, respectively). CONCLUSIONS: There was an increase in the biofilm formation among S. aureus isolated from pediatric patients with sepsis with a significant increase in MRSA. The agr group I was the main agr gene among the isolated S. aureus. Moreover, agr I was the predominant gene in MRSA isolates and was significantly associated with biofilm formation.

Accumulation of Microcystin from Oscillatoria limnetica Lemmermann and Microcystis aeruginosa (Kützing) in Two Leafy Green Vegetable Crop Plants Lactuca sativa L. and Eruca sativa.

The use of contaminated water to irrigate crop plants poses a risk to human health from the bioaccumulation potential of microcystins (MCs) in the edible tissues of vegetable plants. The main objective of this study is to determine the concentration of total microcystins (MC-LR and MC-RR) in leafy green plants (Lactuca sativa L. var. longifolia and Eruca sativa) that have previously been irrigated with polluted water. Integrated water samples were collected by cleaned plastic bottles at a depth of about 30 cm from one of the sources of water used to irrigate agricultural lands for crop plants. At the same time, samples from plants were also collected because this water from the lake farm is used for the irrigation of surrounding vegetable plants such as Lactuca sativa L. var. longifolia and Eruca sativa. The dominant species of cyanobacteria in water samples are Microcystis aeruginosa (Kützing) and Oscillatoria limnetica Lemmermann, which were detected with an average cell count 2,300,000 and 450,000 cells/mL, respectively. These two dominant species in water produced two MCs variants (MC-LR, -RR) that were quantified by high-performance liquid chromatography (HPLC). Dissolve and particulate MCs were detected in the irrigation waters by HPLC with concentrations of 45.04-600 µg/L. MCs in the water samples exceeded the WHO safety limit (1 µg/L) of MC in drinking water. In addition, the total concentration of Microcystin in Lactuca sativa L. var. longifolia and Eruca sativa were 1044 and 1089 ng/g tissues, respectively. The estimated daily intake (EDI) of microcystins by a person (60 kg) consuming 300 g of fresh plants exceeded the total daily intake guidelines (0.04 µg kg-1 body weight) for human food consumption. According to the findings of this study, irrigation water and plants used for human consumption should be tested for the presence of MCs regularly through critical and regularly monitored programs to prevent the accumulation and transfer of such toxins through the food web.

Viral pathogens of acute gastroenteritis in Egyptian children: role of the parechovirus.

BACKGROUND AND AIM: Human parechovirus (HPeV) has emerged as a pathogen associated with acute gastroenteritis (AGE). AIM: To detect the presence of HPeV in the stool samples from Egyptian children with AGE seeking care and the possibility of its co-infection with other enteric viruses. METHODOLOGY: One hundred stool samples were collected from children attending Mansoura University Children's Hospital with AGE. HPeV and astrovirus were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). At the same time, detection of rotavirus antigen and norovirus was achieved by enzyme-linked immunosorbent assay and rapid immunochromatographic method, respectively. RESULTS: The most frequently detected virus was rotavirus (39%), followed by norovirus (27%), HPeV (19%), and astrovirus (12%). Interestingly, the single infection with HPeV was 5%. Among the 19 HPeV positive samples, the co-infection of HPeV with other enteric viruses was detected in 9(43.9%) for rotavirus, 7(36.8%) for norovirus, 2(10.5%) for astrovirus, in 3(15.8%) for rotavirus and norovirus and 1(5.3%) for norovirus and astrovirus. Regarding the clinical presentation, there was no significant difference between children infected with HPeV alone and those infected with viruses other than HPeV alone; fever (p = 0.3), vomiting (p = 0.12), abdominal pain (p = 0.12), and grades of severity (P = 0.82). HPeV alone infected children were of mild severity (60%), and their main presenting symptom was fever (60%). CONCLUSIONS: Detection of HPeV as a single viral pathogen in the stool of some children with AGE showed that this virus could be a causative agent of AGE in Egyptian children. Therefore, HPeV could be included as one of the viruses screened for AGE diagnosis in children in Egypt.

The frequency of periodontitis in end-stage renal disease on hemodialysis in a sample of Egyptian population: multi-center clinical cross-sectional study.

BACKGROUND: There is a general assumption that periodontal disease is highly prevalent among patients with chronic renal failure undergoing hemodialysis. The aim of the study to estimate the frequency of periodontitis in patients on hemodialysis among a sample of the Egyptian population, as well as the correlation between different clinical parameters of periodontal status with serum creatinine and blood urea. This may rule out the bidirectional relationship between periodontitis and renal failure in patients on hemodialysis. METHODS: The study was conducted on 263 hemodialysis patients (165 males and 98 females) at three dialysis centers in Benha Governorate, Egypt (Benha Hospital, Tukh hospital, Qalyub hospital). Periodontal parameters including plaque index (PI), gingival index (GI), clinical attachment level (CAL), and probing pocket depth (PPD) had been recorded in these patients. Serum urea and creatinine levels had been measured, the data had been collected and undergone statistical analysis. RESULTS: Frequency of periodontitis was 85.6% with stage III is the most prevalent stage. There was a significant positive strong correlation between age and periodontitis stage (rs = 0.707, p < 0.001). There was a positive correlation between clinical parameters and serum creatinine level. CONCLUSION: In the present study, a high frequency of periodontitis had been found among ESRD patients on hemodialysis in the severe form (stage III) periodontitis. There was a significant direct correlation between the severity of periodontitis and CAL with a duration of hemodialysis. There was a weak insignificant association between periodontal indices (PD, BOP, and plaque score) and duration of hemodialysis.

Serum interleukin 33 levels and single nucleotide polymorphism rs1929992 in Egyptian patients with chronic asthma.

Bronchial asthma is a common chronic inflammatory disease affecting the airway. Cytokines have a pivotal role in regulation of the immune response, and in development of asthma. Interleukin 33 is a newly discovered member of cytokines, belongs to interleukin 1 family. Previous studies have reported that expression of IL33 is associated with bronchial asthma. This study aimed to evaluate the prevalence of interleukin 33 (IL33) single nucleotide polymorphism (SNP) rs1929992 in asthmatic patients and determine the relation of IL33SNP to IL33 serum level. The Results of RFLP were validated by using sterile distilled water. This study included 100 patients from Egypt, Beni Suef governorate (Upper Egypt) and Mansoura governorate (Delta region), complaining of chronic asthma and 100 control subjects with matched sex and residence. Blood samples from study subjects were used for determination of serum IL33by ELISA and IL33 SNP rs1929992 by PCR-RFLP. There was no significant difference between the proportions of IL33 SNP rs1929992 genotypes in asthma patients and the control group. Allele 'A' predominates in asthmatics though this did not achieve statistical significance (P=0.071). IL33 level was compared in the three IL33 SNP rs1929992 genotypes; G/G, G/A, and A/A, and it revealed no significant difference (P = 0.958). The association between IL33 with asthma showed that the log-additive model is the best inheritance model which marks allele 'A' as the risk allele. In contrast, IL33 serum level was significantly higher in severe asthma than the moderate asthma and the mild type (P<0.0005). Spearman's correlation test showed that IL33 level rises as asthma severity increases (rs=0.880, P<0.0005). In conclusion our data revealed no evidence that SNP of IL33 rs1929992 may contribute to the development of asthma in Egyptian population. However, there is a strong positive correlation between IL33 serum level and asthma severity.

HSP70 as a Diagnostic and Prognostic Marker in Egyptian Women With Breast Cancer.

BACKGROUND: Heat shock protein 70 (HSP70) is a significant cellular stress response protein that has intrinsic and extrinsic pathways to protect cells against apoptosis. It is one of the most induced proteins in cancer cells. The aim of the present study is to investigate the significant role of the HSP70 expression in Egyptian patients with breast cancer (BC) and its potential to be as a diagnostic and prognostic marker. MATERIALS AND METHODS: HSP70 was examined in 155 cases in this prospective study; patients were subdivided into 3 groups: 60 patients with malignant metastatic disease, 60 patients with malignant non-metastatic disease, and 35 patients with benign lesions as control. HSP70 expression was detected using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). RESULTS: Most cases of breast cancer expressed HSP70 in both serum (98.3%) and tumor tissue (90%). A strong positive correlation was found between HSP70 IHC and ELISA (r = 0.811). The mean HSP70 levels, as detected in both patients' serum by ELISA and tumor tissue by IHC, was significantly higher in patients with BC than in benign cases (P = .001). HSP70 was significantly higher in patients with metastatic BC than in those with non-metastatic BC (P = .001). HSP70 showed positive correlation with tumor size (pT stage) and number of lymph node metastases (P ≤ .001). CONCLUSION: HSP70 is over-expressed in patients with metastatic and non-metastatic BC than in benign cases. A high level of HSP70 either in patient's serum or in tumor tissue correlated significantly with advanced disease in patients with BC. This present study suggests that HSP70 can serve as a BC biomarker for early screening, diagnosis, and follow-up.

Concentrations of cylindrospermopsin toxin in water and tilapia fish of tropical fishponds in Egypt, and assessing their potential risk to human health.

Unlike microcystin, cylindrospermospin (CYN) concentrations in fishpond water and their accumulation in fish tissues have been largely unexplored. This study determined CYN levels in water and tilapia fish organs from three tropical fishponds in southern Egypt. Water and fish samples were collected monthly from fishponds for 12 months (Oct 2012 to Sep 2013). The results revealed that six CYN-producing species of cyanobacteria dominated phytoplankton populations and formed blooms in these fishponds during warm months. Among these species, Anabaena affinis, Planktothrix agardhii, Cylindrospermopsis catemaco, and C. philippinensis were assigned as CYN producers for the first time in the present study. The highest cell densities of CYN-producing species in fishponds were recorded in August and September 2013, correlating with high temperature, pH and nutrient concentrations. Dissolved CYN was found in fishpond waters at levels (0.3-2.76 µg L-1) very close to those of particulate CYN (0.4-2.37 µg L-1). CYN was also estimated in tilapia fish organs at levels up to 417 ng g-1 in the intestines, 1500 ng g-1 in the livers, and 280 ng g-1in edible muscles. Compared to the recommended guideline (0.03 µg kg-1 day-1), the estimated daily intake (EDI) of CYN in our samples of edible muscles exceeded this limit by a factor of 1.3-14 during summer and autumn. This might represent a risk to human health upon consumption of such contaminated fish muscles. Therefore, fishponds worldwide should be monitored for the presence toxic cyanobacteria to protect humans from their potent toxins.

Bioavailability of bound microcystins in mice orally fed with contaminated tilapia edible tissues: Implications to human health.

This study investigates for the first time in vivo potential release of bound microcystins (MCs) from edible fish tissues. Bound MCs were released in the mouse digestive system and reached the liver (2.1-14.3 ng g-1) and blood (1-5 ng ml-1). The released MCs were active and negatively affected liver functions of treated mice. The estimated daily intake (EDI) for bound MCs (93.5 µg kg-1 day-1) is about 2300 times higher than the WHO safe EDI (0.04 µg kg-1 day-1), compared to lower EDI for free MCs (0.002 µg kg-1 day-1). Therefore, bound MCs in fish tissues should be considered when fish are monitored for human consumption.

Impact of CYP1A1, GSTP1 and XRCC1 genes polymorphisms on toxicity and response to chemotherapy in childhood acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The interindividual genetic variations in drug metabolizing enzymes and DNA repair genes influence the efficacy and toxicity of numerous chemotherapeutic drugs affecting the treatment outcome. AIM OF THE WORK: The aim of the study was to investigate the impact of drug metabolizing CYP1, GSTP1 and DNA repair (XRCC1) genes polymorphisms on the toxicity and response to chemotherapy in childhood ALL. PATIENTS AND METHODOLOGY: Ninety seven ALL pediatric patients were genotyped for CYP1A1, GSTP1 ILe105Val and XRCC1 Arg194Tryp single nucleotide polymorphisms (SNPs) using PCR-RFLP. RESULTS: No statistically significant differences were observed between the wild and variant (homozygous and heterozygous) genotypes of the polymorphisms studied in CYP1A1, GSTP1 or XRCC1 genes regarding age, total leukocyte count, immunophenotyping, cytogenetic or risk group. The SNPs in CYP1A1, GSTP1 and XRCC1 genes did not show significant association with complete remission (CR) rate, overall survival (OS) or event free survival (EFS). However, XRCC1 Arg194Trp SNP was associated with higher drug toxicity; carriers of variant genotypes (CT and TT) had a significantly higher frequency of myelosuppression compared to those with the wild CC genotype (21/43[48.8%]) compared to (14/54[25.9%]) (p=0.020). The analysis of the combined effect of studied SNPs did not show any significant association with patient outcome. CONCLUSION: Our study reported a significant association between the DNA repair gene polymorphism and myelosuppression in childhood ALL patients. Adjustment of the dose of chemotherapeutic agents according to XRCC1 Arg194Trp polymorphism may improve outcome in cases with risk of toxicity.