Correlation of Genetic Polymorphism of CYP3A5 to Cyclophosphamide Efficacy and Toxicity in Rhabdomyosarcoma Pediatric Egyptian Cancer Patients.

OBJECTIVES: Rhabdomyosarcoma (RMS) accounts for 50% of soft tissue sarcomas and 7% of pediatric malignancies. Cyclophosphamide (CPA) is the cornerstone of therapy and is a prodrug that is activated by the highly polymorphic drug-metabolizing enzyme CYP3A5. We aim to examine the possible CYP3A5 polymorphism association with CPA efficacy, survival outcomes, and toxicity in Egyptian pediatric RMS patients. METHODS: The three non-functional SNPs, CYP3A5*3 rs776746 (C_26201809_30), CYP3A5*6 rs10264272 (C_30203950_10), and CYP3A5*7 rs41303343 (C_32287188_10) were genotyped by real-time PCR. We conducted a cohort retrospective study of 150 pediatric RMS patients treated with CPA-based first-line treatment to analyze the association between these genotypes and CPA efficacy/toxicities in RMS patients. KEY FINDINGS: The frequency of having normal, intermediate, and poor metabolizers was 4.7%, 34%, and 61.3%, respectively. There was an association between these different phenotypes, genotypes, and CPA efficacy/toxicity. Hemorrhagic cystitis and pancytopenia were present in all patients, while nephrotoxicity incidence was 87.3%. There was a notable difference in the occurrence of hemorrhagic cystitis among CYP3A5 intermediate metabolizers *1/*3, *1/*6, and poor metabolizers *3/*3, *3/*6 with a significance level of p<0.05. Neither CYP3A5*7 polymorphism nor *6/*6 genotype was identified in our study. CONCLUSION: Our results demonstrate that CYP3A5*3 (rs776746) and CYP3A5*6 (rs10264272) have a great association with CPA efficacy and toxicity in RMS patients.

Optimizing vancomycin therapeutic drug monitoring compliance in pediatric oncology: towards personalized medication management.

Aim: Vancomycin, a crucial treatment for Gram-positive bacteria, necessitates therapeutic drug monitoring (TDM) to prevent treatment failures. We investigated the healthcare professional's compliance toward TDM of vancomycin recommendations and follow-up levels. Materials & methods: We collected data from 485 patients who received vancomycin in the Children's Cancer Hospital Egypt 57357 medical records system (Cerner) over 4 months, from January to April 2020. Results: Our data shows that only 54% of patients had TDM requests from healthcare professionals for the total patients who received vancomycin treatment. The healthcare professionals' compliance with the recommendations was 91.7%, while the follow-up levels were 66.7%. Conclusion: While overall adherence to recommendations is strong, enhancing compliance with follow-up levels remains a priority for improvement.

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De novo regeneration of dentin pulp complex mediated by Adipose derived stem cells in an immunodeficient albino rat model (Histological, histochemical and scanning electron microscopic Study).

Background: Dental tissue engineering is an alternative procedure for restoring damaged dental tissues. Adipose-derived stem cells are a new source of cells for regenerative endodontics in combination with scaffold materials. The descriptive data about this regenerative process is still insufficient. Objective: To evaluate the regenerative potential of Adipose-derived stem cells using a self-assembling polypeptide scaffold for the dentin-pulp complex in an emptied root canal space. Material and Methods: 40 root segments of human single-rooted teeth were transplanted into the albino rats' dorsal subcutaneous tissue. Root segments were divided into two groups: group I contained only a self-assembling polypeptide scaffold, and group II contained fluorescent-labeled Adipose-derived stem cells embedded in a self-assembling polypeptide scaffold. The newly formed tissues were assessed on the 60th and 90th days post-transplantation using routine histological examination, Masson trichrome staining, and scanning electron microscopy. Results: Group I showed granulation tissue without any signs of predentin formation or odontoblast-like cells. Group II revealed the presence of predentin tissue along the dentin margin, with arranged odontoblast-like cells. An organized connective tissue with abundant vasculature and calcific masses was observed in the pulp space. Conclusion: Adipose-derived stem cells can be considered as alternative stem cells for regenerating the dentin-pulp complex. Dentin pulp complex regeneration utilizing a self-assembling polypeptide scaffold alone would not yield successful results.

Efficacy and Toxicity of Vincristine and CYP3A5 Genetic Polymorphism in Rhabdomyosarcoma Pediatric Egyptian Patients.

BACKGROUND: Rhabdomyosarcoma (RMS) is a rare cancer that develops in soft tissue, particularly skeletal muscle tissue and occasionally hollow organs like the bladder or uterus. Vincristine (VCR) is the main therapy used in treatment of RMS, it is an alkaloid produced from vinca and it is one of the most commonly prescribed drugs in pediatric oncology for the treatment of a number of tumors. The CYP3A5 enzyme is responsible for vincristine metabolism. The effect of CYP3A5 genetic polymorphism on the efficacy and toxicity of VCR on RMS patients still needs further research. METHODS: Genotyping for CYP3A5 SNPs rs776746, rs10264272 and rs41303343 was performed using Taqman Real-Time PCR assays in a retrospective cohort study of 150 RMS pediatric patients treated with vincristine. The relationship between these genotypes and RMS survival was then examined. RESULTS: We found that patients with CYP3A5*3/*3 had the highest incidence of vincristine-induced neuropathy reaching 61.3%. Patients with CYP3A5*1/*3, CYP3A5*3/*6 and the normal metabolizers with CYP3A5*1/*1 had frequencies of 22%, 10.7%, and 4.7%. patients with the lowest frequency of 1.3% were those with the CYP3A5*1/*6 genotype. There was no correlation between the genotypes of CYP3A5*3, CYP3A5*6, CYP3A5*7, and RMS survival. Initial risk, metastasis, response, convulsions, unsteady gait and hepatotoxicity grade had a significant effect on overall survival with p<0.05. CONCLUSION: CYP3A5*1/*1 have less severe vincristine-induced neuropathy than CYP3A5 *1/*3, CYP3A5 *1/*6 and CYP3A5 *3/*3, CYP3A5 *3/*6. There is a significant influence of CYP3A5 mutation on neuropathy grade and assist of ADL as a part of neurotoxicity.

Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies.

ABSTRACTSmall molecule therapy is a critical component of targeted anticancer treatment, with tyrosine kinase inhibitors (TKIs) being the first compounds to treat the clonal Chronic Myelogenous Leukaemia (CML) translocation t (9;22) (q34; q11) effectively since 2001. TKIs, such as imatinib, have improved the 10-year survival rate of CML patients to 80%. They bind the BCR::ABL1 kinase and inhibit downstream signaling pathways. However, therapy failure may be seen in 20-25% of CML patients due to intolerance or inadequacy related to BCR::ABL1 dependent or independent mechanisms. This review aimed to summarize current treatment options involving TKIs, resistance mechanisms and the prospective approaches to overcome TKI resistance. We highlight BCR::ABL1-dependent mechanisms of TKI resistance by reviewing clinically-documented BCR::ABL1 mutations and their consequences for TKI binding. In addition, we summarize BCR::ABL1 independent pathways, including the relevance of drug efflux, dysregulation of microRNA, and the involvement of alternative signaling pathways. We also discuss future approaches, such as gene-editing techniques in the context of CML, as potential therapeutic strategies.

Comparison between platelet-rich plasma (PRP) and mechanically emulsified fat grafts in management of chronic wounds.

BACKGROUND: chronic wounds represent a challenge in treatment, due to diverse pathogenesis, resistance to ordinary treatment complex and lack of direct methods of treatment In this study, the aim is to compare the effect of Platelet -rich plasma (PRP) and mechanically emulsified fat grafts on the outcome of the healing process of chronic wounds. PATIENTS AND METHODS: In the current study, 30 patients with chronic wounds were divided into two groups (Group I, 15 patients had application of PRP on chronic wounds). Whereas (Group II, 15 patients had application of mechanically emulsified fat on chronic wounds). In both groups assessment of the healing rates and histopathological changes that were determined by observing the parameters of wound healing, including peri-lesional skin quality, observation of the wound size and depth, assessment of the pain indicated by Visual analog scale score. RESULTS: Patient were followed up for 6 months. Group II showed a better healing rate 64% in comparison to Group I 55%. Wound parameters and pain score were recorded in both groups with no statistically significant difference. CONCLUSION: Both PRP and mechanically emulsified fat grafts were found to be efficient treatment modalities in management of chronic "non-healing" wounds. But mechanically emulsified fat grafts represent a better treatment method for chronic wounds.

Healthcare workers' mental health and perception towards vaccination during COVID-19 pandemic in a Pediatric Cancer Hospital.

The consistent increase of Coronavirus disease 2019 (COVID-19) cases parallel with the rate of deaths and the controversial response regarding the vaccines caused an increase in the burden of psychological diseases. This study aimed to evaluate the psychological condition of healthcare workers (HCWs) in a pediatric cancer hospital and to identify the knowledge, attitude, and perception (KAP) of HCWs toward COVID-19 vaccination. A cross-sectional observational study was conducted between April to May 2021. A validated, confidential survey was employed to measure the mental health of HCWs and the KAP toward COVID-19 vaccines. The total responses were 395, of which 11.4% physicians, 18.5% pharmacists, and 70.1% were nurses. Sixty-six percent of HCWs had different degrees of anxiety and depression. Nurses significantly accounted for the highest anxiety levels (P = 0.003), while the cumulative anxiety score was significantly higher in HCWs who had a positive history of COVID-19 infection (P = 0.026). Although 67.6% of HCWs believe that "vaccines are essential for us,", the vaccination rate was 21.3%. The Factors associated with not receiving the vaccine were younger ages (P = 0.014), nurses (P = 3.6987 × 10-7), negative history of COVID-19 infection (P = 0.043) and believing that infections can happen after taking the vaccine (P = 1.5833 × 10-7). Healthcare organizations must take serious intervention to decrease the mental load on HCWs and facilitate the vaccination process.

Results of Wedgeless Distal Femoral Osteotomy for the Treatment of Genu Valgus Deformity.

INTRODUCTION: Coronal plane knee deformities are common disorders affecting adolescents. Valgus deformities (tibiofemoral angle (TFA) > 12-15 degrees and intermalleolar distance (IMD) > 10 cm) often require corrective osteotomy and a wedgeless "V" distal femoral osteotomy is a good treatment option for such deformities. MATERIALS AND METHODS: Thirty adolescent patients (13-17 years) with valgus deformities were included. Patients with severe collateral ligament instability, subluxation, and sagittal plane deformity > 15 degrees or genu valgum due to tibial deformity were excluded. Preoperative clinical (Bostman's knee score, IMD, and knee-flexion test) and radiological evaluations were done. The surgery (wedgeless distal femoral V osteotomy) was performed and stabilized with two Kirschner wires (K-wires). Postoperative clinical and radiological parameters were recorded including complications. RESULTS: The preoperative TFA was 20.23 ± 3.63 degrees, which reduced to 5.5 ± 0.73 at six months postoperatively. The preoperative IMD was 12.45 ± 2.2 cm, which reduced to 1.63 ± 0.32 cm at six months. The mean mechanical axis deviation (MAD) and lateral distal femoral angle (LDFA) were recorded as 2.8 ± 0.39 and 87.7 ± 0.83, respectively, and the differences were statistically significant from preoperative values. The Bostman score was 26.2 ± 1.79 at three months and 29.47 ± 0.9 at six months. The complications included infection in two patients, a hypertrophic scar in one patient, and common peroneal neuropraxia in one patient. CONCLUSION: Wedgeless distal femoral osteotomy with K-wire fixation is a viable option for correction of genu valgus deformity with potential advantages of minimal blood loss, no leg length discrepancy, non-rigid fixation, and early union as compared to other treatment options.

Knowledge, attitudes and practices of Egyptian healthcare professionals toward therapeutic drug monitoring service as a principal component of personalized medicine.

Aim: To assess pharmacists' and physicians' knowledge, attitudes and practices toward therapeutic drug monitoring (TDM) service at the Children's Cancer Hospital Egypt 57357. Materials & methods: This was a single-site cross-sectional study where all practicing pharmacists and physicians were eligible to participate. Results: A statistically significant difference in the knowledge scores between pharmacists and physicians (p = 0.022) was found. In general, attitudes toward TDM among pharmacists and physicians were positive. Regarding practices, pharmacists were more likely than physicians to agree or strongly agree that they have studied some scientific references on TDM (p = 0.034), but more physicians recommend the TDM service (p = 0.046). Conclusion: A multidisciplinary educational program in Egypt for TDM for both medicine and pharmacy staff will improve interprofessional collaboration in the clinical setting, leading to better personalized medication management.

The objective of the present survey was to evaluate the knowledge, attitudes and practices of pharmacists and physicians toward therapeutic drug monitoring (TDM) services at the Children's Cancer Hospital Egypt 57357. TDM is defined as 'measuring the amount of specific drugs in patients' blood to ensure that the concentrations of administered drugs are both effective and safe'. A single-centered study was conducted at the CCHE where all pharmacists and physicians participated. There was a remarkable difference in the knowledge scores between pharmacists and physicians. Generally, both pharmacists and physicians demonstrated positive attitudes toward TDM. In real-life practice, pharmacists were more likely than physicians to agree that they had scientific evidence about TDM. Multidisciplinary educational programs for TDM among physicians and pharmacists would improve interprofessional collaboration for the benefit of patients in Egypt.

Knowledge, attitudes and practice regarding pharmacovigilance and adverse drug reaction reporting among physicians and pharmacists in Egypt: a step toward personalized medicine implementation.

Aim: To assess the knowledge, attitudes, and practices of the healthcare professionals working at Children's Cancer Hospital Egypt regarding pharmacovigilance (PV) and adverse drug reaction (ADR) reporting, in addition to the ADR reporting barriers. Materials & methods: A cross-sectional study was conducted at Children's Cancer Hospital Egypt from July to September 2021 using a validated questionnaire. Results: About 37 physicians (20.3%) and 145 pharmacists (79.7%) responded to the survey. Overall, the knowledge (median: 40%) and practice (median: 50%) of PV and the reporting of ADRs were low; however, attitudes were mostly positive. The main barrier to reporting ADRs was The difficulty of determining whether or not ADRs occurred (42.3%). Conclusion: Understanding of PV and ADR reporting could improve the huge gap between ADRs experienced and ADRs reported. In order to be able to assess the impact of personalized medicine implementation, adequate ADR reporting should be well established.

Since no medication is completely safe, many of them are associated with multiple adverse reactions that may affect patients' health in terms of morbidity and, even worse, mortality. These concerns greatly increase the importance of reporting adverse drug reactions (ADRs), which highlights the essential role of pharmacovigilance (PV) centers. This study was performed at Children's Cancer Hospital using a validated questionnaire; to collect information on healthcare professionals' demographics and their knowledge of, attitudes toward and practices in PV; analyze reasons for the the under-reporting of ADRs; and recommend possible ways to improve reporting. The majority of the healthcare professionals had poor knowledge and practice of PV and ADR reporting, which clearly explains the huge gap between ADRs experienced and ADRs reported. However, they have a positive attitude toward PV and ADR reporting.

The Use of Fluoroscan in Hand Clinic During the Covid Pandemic to Optimise Conservative Treatment.

Introduction The study assessed the use of Fluoroscan (Hologic, Inc., Marlborough, MA) in hand clinic as advised by the British Orthopaedic Association (BOA) during the COVID-19 pandemic to facilitate treatment of fractures requiring manipulation and reduce admissions to evaluate if this should be embedded in practice permanently. Method Eighty-three wrist and hand fractures requiring manipulation were identified between April 2020 and March 2021. Demographics, mechanism of injury, timing of intervention, radiological outcome, further intervention and functional assessment by QuickDASH scoring were recorded. Results Sixty-eight cases were manipulated within the first week of fracture, simple pain control measures were used, and dose area product (DAP) averaged 1.3 Gy cm2 well below the dose limit set by the trust. Satisfactory fracture reduction was achieved in 59 cases avoiding admission. Further surgical intervention was offered to 24 patients: five re-manipulated while 19 had operation, all with a good functional outcome. Conclusion Fluoroscan use in fracture clinics achieved effective fracture control in 77% of cases. The use of Fluoroscan avoided admissions for surgery during the pandemic and lengthy clinic visits, four out of five did not need admission.

Novel concepts and early results of repairing common arterial trunk.

OBJECTIVES: Common Arterial Trunk (CAT) continues to have a very poor prognosis globally. To address that, we have developed a novel technique targeting key concepts for the correction of all components of the anomaly, using autologous arterial tissue. This aims to enhance results, availability worldwide, and importantly to avoid the need for repeated reoperations. METHODS: From January 2019 to 4 January 2021, all patients with isolated CAT had repair of the defect using autologous arterial trunk tissue with direct right ventricle (RV) to pulmonary artery (PA) connection. Clinical outcomes, follow-up which included multi-slice computed tomography 3D segmentation and 4D cardiovascular magnetic resonance flow, are presented. RESULTS: Twenty patients were included in the study (median age 4.5 months). There were 2 hospital deaths due to systemic infection and pulmonary hypertensive crisis, respectively. Following discharge all patients remained asymptomatic with no signs of heart failure and improved pattern of growth (median follow-up: 8 months). Early postoperative 3D segmentation showed a conical shaped neo-right ventricular outflow chamber connecting the body of the RV to the main PA through a valveless ostium, and normal crossing of PA and neo-aorta. 4D cardiovascular magnetic resonance pattern of flow showed normal rapid laminar flow through the atrioventricular valves followed by a vortex towards the outflow tracts. There was laminar flow through the neo-aorta and neo-PA with velocity not exceeding 2.5 m/s. The PA regurgitant fraction was 25 ± 5% and was limited to early diastole. CONCLUSIONS: The initial results of utilizing the key concepts, using autologous arterial tissue for the repair of CAT, are encouraging, both clinically and by multimodality imaging.

Peripheral Neurectomy for Trigeminal Neuralgia: A Report of Seventeen Cases and Review of the Literature.

BACKGROUND: Surgical intervention for trigeminal neuralgia (TN) is indicated if there is a failure of the medical treatment. Peripheral neurectomy is one of the oldest surgical procedures for TN. OBJECTIVE: The aim is to evaluate the clinical outcome and the recurrence rate following peripheral neurectomy for the management of TN. PATIENTS AND METHODS: This was a retrospective cohort study of 17 patients with classical TN treated by peripheral neurectomy. The visual analogue scale (VAS) was used for pain assessment preoperatively and during the follow-up period. The outcome of surgery was graded as a marked, moderate, or mild improvement. Kaplan-Meier analysis was used for the time to recurrence to predict the probability of recurrence at any given time following the procedure. RESULTS: The mean pain-free interval was 29.3 ± 16.3 months. At 2 and 5 years of the follow-up period, the mean VAS improved significantly (P < 0.001 and P = 0.042 respectively). Thirteen patients had marked improvement of pain. There was recurrence of pain in 4 patients (23.5%). By Kaplan-Meier analysis, the survival rate without recurrence at 2, 3, 4, and 5 years following the procedure were 92.9%, 79.6%, 59.7%, and 29.8%, respectively. The mean preoperative Hospital Anxiety and Depression Scale-Anxiety and Depression scores significantly improved on the last follow-up visit following the procedure (P < 0.001 for both). CONCLUSION: Peripheral neurectomy provides short to medium-term good pain control for patients with TN. The preoperative severity of pain, anxiety, and depression levels improved markedly after the procedure.

Limb Length Inequality in Patients After Primary Total Hip Arthroplasty: Analysis of Radiological Assessment and Influencing Risk Factors Based on a District General Hospital Experience of 338 Cases.

Background and objective Limb length inequality (LLI) is a frequent and recurring issue after total hip arthroplasty (THA). It is often a source of patient dissatisfaction and litigation. This study reviewed the incidence of LLI in a UK District General Hospital in light of published evidence and identified the preoperative and intraoperative risk factors for LLI. Methods This was a retrospective study involving 380 consecutive unilateral primary total hip replacements over a period of 12 months. Patient demographics, clinical, radiological, and operative details were collected from the National Joint Registry (NJR) database and hospital records. The limb length was measured radiologically [OrthoView WorkstationTM (Materialise UK, Southampton, UK)], pre- and postoperatively, by two authors. They assessed the vertical distance between the intra-acetabular teardrop line and the medial apex of the lesser trochanters. After excluding complex primary, revision cases, tilted X-rays, and hip replacement for trauma patients, 338 cases were included in the final analysis. Results The mean postoperative LLI was 2.7 mm with a standard deviation (SD) of 6.56 mm. Only 5.3% of patients had LLI >15 mm. None of the studied variables showed a statistically significant correlation with LLI. Even with the apparent difference in the mean LLI between templating and not templating before surgery (2.19 vs. 3.53), the p-value was 0.06, which was below the level of statistical significance. There was a weakly positive Pearson correlation between body mass index (BMI) and the incidence of lengthening of the limb. Conclusion The cause of LLI after THA is multifactorial. No single factor can be singled out as the most significant contributor to this complication.

A New Technique for Shaping the Aortic Sinuses and Conserving Dynamism in the Remodeling Operation.

BACKGROUND: Preserving dynamism and recreating the sinuses in the Dacron graft are thought to be important for optimizing results of aortic valve-conserving operations. METHODS: We describe a novel technique that preserves dynamism and recreates the sinotubular junction. In addition, it tailors 3 sinuses of defined longitudinal and transverse curvatures in a straight Dacron tube during the operation. The technique has been used in 6 patients with varied aortic root pathology. We performed preoperative and postoperative multimodality imaging using computerized image analysis as well as 3-dimensional models. RESULTS: There was no early or midterm death. Upon discharge, patients were clinically well, with echocardiographic evidence of minimal (3 patients) or mild (3 patients) aortic regurgitation. Computed tomography and cardiac magnetic resonance imaging with extensive image analysis of the aortic root size, shape, and function showed partial or complete normalization of these parameters. This included the shape and dynamism of the aortic annulus and the size and shape of the geometric (effective) orifice. The 4-dimensional magnetic resonance imaging pattern of flow in the sinuses and ascending aorta showed favorable vortices in the sinuses, right-handed helical flow, and marked diminution of energy loss in the ascending aorta. CONCLUSIONS: The novel technique described here is simple, practical, and cost-effective because it uses a widely available straight Dacron tube. The technique does not use rigid internal or external support. The early results are encouraging. Larger series with longer follow-up are required.

Unraveling heterogeneity of the clinical pharmacogenomic guidelines in oncology practice among major regulatory bodies.

Pharmacogenomics (PGx) implementation in clinical practice is steadily increasing. PGx uses genetic information to personalize medication use, which increases medication efficacy and decreases side effects. The availability of clinical PGx guidelines is essential for its implementation in clinical settings. Currently, there are few organizations/associations responsible for releasing those guidelines, including the Clinical Pharmacogenetics Implementation Consortium, Dutch Pharmacogenetics Working Group, the Canadian Pharmacogenomics Network for Drug Safety and the French National Network of Pharmacogenetics. According to the US FDA, oncology medications are highly correlated to PGx biomarkers. Therefore, summarizing the PGx guidelines for oncology drugs will positively impact the clinical decisions for cancer patients. This review aims to scrutinize side-by-side available clinical PGx guidelines in oncology.

Assessment of healthcare professionals' knowledge, attitudes, and perceived challenges of clinical pharmacogenetic testing in Egypt.

Aim: We evaluated healthcare practitioners' perspectives regarding clinical pharmacogenetics in Cairo, Egypt. Materials & methods: We administered a paper-based survey to pharmacists and physicians practicing at Children's Cancer Hospital Egypt. The survey assessed practitioners' knowledge, attitudes, and perspectives about pharmacogenetic testing. Results: The study included 184 respondents (67.9% pharmacists; 32.1% physicians. Overall, the pharmacogenetic knowledge was low (mean = 41.7%) but attitudes toward pharmacogenetic testing and its potential clinical application were generally positive. Pharmacists responded more favorably than physicians to statements attributing the responsibility of applying pharmacogenetics in the clinical setting to their profession. However, several challenges were identified; the most common being: lack of pharmacogenetic knowledge and skill, lack of pharmacogenetic testing devices, and limited funding. Conclusion: Future efforts to promote pharmacogenetic implementation should focus on foundational education, practical training, and exploration of potential funding sources.

A Comparison between Three Different Automated Total 25-hydroxyvitamin D Immunoassay Methods and Ultra Performance Liquid Chromatography.

OBJECTIVE: Vitamin D is a fat soluble vitamin responsible for calcium metabolism and more recently discovered effects. This led to an increase in requests for vitamin D test by clinicians. New automated assays have been introduced for 25-hydroxyvitamin D measurement. METHODS: Results from these new method have to be related to a Standard method to obtain best results for practical usage. In our study, one hundred venous blood samples were analyzed for 25-OH vitamin D on three immunological methods in our lab and correlated with ultra-performance liquid chromatography (UPLC) method as a reference method. RESULTS: Statistically analysis of results obtained for correlations between the 3 methods against the reference UPLC was done by Spearman's Correlation. It showed positive correlation in all methods with significant p value < 0.001. Differences and biases between methods were evaluated using a Bland-Altman plot and Cohen's Kappa agreement. Best agreement was found in Cobas 6000 followed by the Access2 then comes Architect.  Conclusions: All immunoassays can be used in routine 25(OH) D measurements, still some methods are better than others. A clinical laboratory must at least be aware of its method to avoid misinterpretation of results.

The utility of 3D printed models in complex percutaneous paravalvular leak interventions.

Paravalvular leaks (PVL) are seen in 5-17% of patients after surgical mitral and aortic valve replacement. This is usually well-tolerated in the majority of patients; however, up to 5% will require re-intervention due to either hemodynamically significant regurgitation or hemolysis requiring repeated blood transfusion. Transcatheter closure of PVLs is becoming the treatment of choice in many patients owing to the high risk of redo surgery, high rates of recurrence with the surgical approach, and substantial improvements in device technology and growing expertise in structural heart disease interventions. Careful selection of the appropriate candidates by the Heart Team with in-depth analysis of clinical and multimodality imaging data is critical to ensuring good short- and long-term outcomes1. The defect is usually oval/crescentic and often serpiginous in nature, which poses significant challenges in choosing the optimal size and number of devices to implant - especially with large size defects. Generally, defects involving more than 25-30% of the sewing ring are deemed unsuitable for percutaneous closure. While the Amplatzer family of vascular plugs (e.g. AVP3 and AVP2) is commonly used for percutaneous closure of PVLs, there are currently no approved dedicated devices for this indication, except the paravalvular leak device (Occlutech) which is not universally available. Small and relatively circular defects can usually be closed using a single plug, conventionally utilizing a size that is 25-30% larger than the mean diameter of the defect. Larger and crescentic defects on the other hand frequently require more than one plug and can be quite challenging in terms of choosing the appropriate size(s)2. We report two cases with very large defects with irregular shape in which 3D printed modeling was extremely useful for bench testing to optimize the number and sizes of devices to be implanted.

Medication compliance and lifestyle adherence in renal transplant recipients in Kuwait.

INTRODUCTION AND AIM: Kidney transplantation is the optimal treatment choice for end stage renal disease; this option needs a major change in the recipients' lifestyle and requires strict adherence to medications. The study aim was to assess the compliance of renal transplant patients to medications and lifestyle modifications in the Hamed Al-Essa Organ Transplant Center in Kuwait. PATIENTS AND METHODS: One-hundred and twenty renal transplant patients were interviewed for their lifestyle behaviors after transplantation, including transplant adherence to their medications, healthy meals, personal hygiene, physical activity, regular out-patient follow up visits, and preventive measures against infection and cancer, in addition to sexual function. The questionnaire used was created by staff of the Faculty of Medicine, Mansura University, Egypt. RESULTS: Sixty percent of the renal transplant patients were compliant with medications and lifestyle. Risk factors associated with poor medication compliance were being Kuwaiti citizens, women, and having had unrelated living donors (p<0.05). Compliance with medications was associated with less transplant related complications (p=0.003). Only 15% of the participants were compliant with low-salt diet, 8% with low-fat, and 11% with low-carb. One fourth of patients were compliant with a daily shower and 20% were physically active. More than 70% of the patients were regularly visiting the out-patient clinic. Compliance to preventive measures against infection was observed in 85% of patients but only 5% were avoiding direct sun exposure. Half of the male patients had sexual dysfunction but only half of them were consulting their nephrologists about it. CONCLUSION: Kidney transplant patients in Kuwait had moderate compliance with medications and lifestyle modifications. Closer assessment is needed to identify the risk factors before and after transplantation to avoid any complications associated with non-compliance.