Sequence Variant Analysis of the APOCII Locus among an Arab Cohort.

Apolipoprotein CII (ApocII) plays a key role in regulating lipoprotein lipase (LPL) in lipid metabolism and transport. Numerous polymorphisms within APOCII are reportedly associated with type 2 diabetes mellitus (T2DM), dyslipidemia, and aberrant plasma lipid levels. Few studies have investigated sequence variants at APOCII loci and their association with metabolic disorders. This study aimed to identify and characterize genetic variants by sequencing the full APOCII locus and its flanking sequences in a sample of the Kuwaiti Arab population, including patients with T2DM, hypertriglyceridemia, non-Arab patients with T2DM, and healthy Arab controls. A total of 52 variants were identified in the noncoding sequences: 45 single nucleotide polymorphisms, wherein five were novel, and seven insertion deletions. The minor allele frequency (MAF) of the 47 previously reported variants was similar to the global MAF and to that reported in major populations. Sequence variant analysis predicted a conserved role for APOCII with a potential role for rs5120 in T2DM and rs7133873 as an informative ethnicity marker. This study adds to the ongoing research that attempts to identify ethnicity-specific variants in the apolipoprotein gene loci and associated LPL genes to elucidate the molecular mechanisms of metabolic disorders.

Association Study of IGF-1 rs35767 and rs6214 Gene Polymorphisms with Cancer Susceptibility and Circulating Levels of IGF-1, IGFBP-2, and IGFBP-3 in Colorectal Cancer Patients.

Early detection of colorectal cancer (CRC) increases the 5-year survival rate by 90%; therefore, non-invasive biomarkers such as measurable circulating proteins for early detection and prognosis are crucial. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and apoptosis. IGF binding proteins (IGFBPs) bind and inhibit the activity of IGF-1. It was inconsistently reported that high IGF-1 and IGFBP-2 and low IGFBP-3 circulating levels are associated with high cancer risk, poor prognosis, and tumor metastasis in several cancers. A total of 175 patients with CRC and 429 controls were enrolled in this study. We genotyped for IGF-1 rs35767 and rs6214 gene polymorphisms and assessed their association with circulating levels of IGF-1 and/or the risk for CRC. We also determined plasma levels of IGF-1, IGFBP-2, and IGFBP-3. Neither rs35767 nor rs2614 were associated with cancer risk or IGF-1 levels in our study cohort. IGF-1 and IGFBP-3 levels were higher in controls than in patients, whereas IGFBP-2 was higher in patients than in controls. Only IGFBP-2 was associated with increased tumor grade but not stage. Therefore, IGF-1, IGFBP-2, and IGFBP-3 may be useful as early detection and prognostic biomarkers in CRC.

Hemoglobin Drop and the Need for Transfusion in Primary Knee Arthroplasty.

Background Blood loss is still a serious adverse effect of total knee replacement (TKR), resulting in Hemoglobin drop and a higher need for blood transfusions. Multiple modalities are used to reduce intra-operative blood loss and hemoglobin drop for this procedure, such as placing a drain intraoperatively and Tranexamic acid (TXA) administration. This study aimed to investigate factors associated with hemoglobin loss and blood transfusion increased demand. Patients and methods We retrospectively looked at 223 patients who underwent primary unilateral or staged bilateral knee arthroplasty by a single surgeon from January 2013 until April 2018 in Salmaniya Medical Complex (SMC), Bahrain. We looked into patients' demographics such as age, gender, preoperative hemoglobin and hematocrit, postoperative hemoglobin and hematocrit, drain insertion intra-operatively, and the administration of Intravenous tranexamic acid intra-operatively. Eighty-three patients had a drain inserted intra-operatively, and sixty-nine patients received intra-venous Tranexamic acid during the procedure. Results Out of 223 patients, 152 patients were included after applying exclusion criteria. The mean hemoglobin (Hb) loss in patients who had a drain inserted was 2.186 g/dL, while patients who received tranexamic acid had a mean of 1.609 g/dL. Multivariable regression analysis revealed that increased blood transfusion requirements postoperatively were significantly associated with reduced pre-operative Hemoglobin levels (p-value .004). Univariable analysis of the hemoglobin drop showed that the use of TXA would reduce Hb loss while a drain would increase Hb drop (p-value .003 and .002, respectively). Moreover, univariable analysis of blood transfusion requirements showed reduced pre-operative Hb, and placing a drain would increase blood transfusion demand (p-value <.001, .044 respectively), while administration of tranexamic acid would reduce blood transfusion demand (p-value 0.05). Conclusion Reducing the need for blood transfusion following primary total knee arthroplasty can be achieved by maintaining preoperative hemoglobin levels, administering tranexamic acid intra-operatively, and avoiding placing an intra-articular drain.

Acute abdomen: Unusual presentation of Herlyn-Werner Wunderlich syndrome.

INTRODUCTION AND IMPORTANCE: The presentation of an acute abdomen has a wide range of differentials. Developmental anomalies are rarely considered as part of the clinical reasoning process due to it being a mimicker of other commoner diseases. The importance of considering such anomalies and recognizing them early is essential in order to prevent complications, such as infertility. CASE PRESENTATION: Our case report presents an approach to a female of pediatric age complaining of right lower abdominal pain mimicking appendicitis. The physical examination and clinical findings were also in line with appendicitis. Thus, the initial work-up focused on that as the top differential. Due to the patient being female, other work-ups were conducted in order to rule out gynecological conditions such as a pelvic ultrasound. The ultrasound findings changed the approach, warranting a CT and MRI. The subsequent diagnosis was Herlyn-Werner-Wunderlich Syndrome. Intervention involved incision and dilation of the vaginal septum as it is the most effective and least traumatic method. On follow-up, the patient's symptoms resolved. CLINICAL DISCUSSION: Rare diseases can mimic common diseases. Clinically, findings of other work-ups indicated a completely different diagnosis than originally suspected. Clinical reasoning thus shifted the focus to another approach and intervention. CONCLUSION: Clinical features of appendicitis, a clinical diagnosis, were most evident. An inappropriate management may have ensued if investigations were not conducted. Ultimately, the case report illustrated the importance of radiological investigations in an acute abdomen.

Vitamin D Intoxication and Nephrocalcinosis in a Young Breastfed Infant.

Numerous studies were performed assessing the benefits and side effects of vitamin D. Vitamin D helps in regulating the calcium and phosphate metabolism leading to a healthy mineral and bone development. Vitamin D intoxication is an uncommon event that leads to hypercalcemia which can be associated with both immediate and late morbidities that can cause severe renal complications. Here, we present a case of a 4-month-old girl with a history of decreased feed and activity due hypercalcemia and high vitamin D level, which led to nephrocalcinosis. The patient received IV fluids, IV diuretics, methylprednisolone, and bisphosphonate in order to normalize the calcium level in blood. With clear verbal and written instructions for the dosage and administration of vitamin D supplements, as well as clear warnings of the potential risks of overdose, vitamin D intoxication could be an easily avoidable condition.

Association analysis of genetic variants in the ghrelin and tumor necrosis factor α genes and the risk for non-Hodgkin's lymphoma in Kuwaitis.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is the most common hematological malignancy in the world. Many etiologic factors have been implicated in the risk of developing NHL, including genetic susceptibility and obesity. Single-nucleotide polymorphisms (SNPs) in Ghrelin (GHRL), an anti-inflammatory hormone, and tumor necrosis factor α (TNF-α), an inflammatory cytokine, have been independently associated with the risk for obesity and NHL. OBJECTIVE: To investigate the association between SNPs in GHRL and TNF-α and the risk for NHL and obesity in Kuwaitis. METHODS: We recruited 154 Kuwaiti NHL patients and 217 controls. Genotyping was performed for rs1629816 (GHRL promoter region), rs35684 (GHRL 3' untranslated region), and rs1800629 (TNF-α promoter region). Logistic regression analysis was performed to assess the association of the investigated SNPs with NHL and the relationship between the selected SNPs with BMI in each group separately. RESULTS: We show that rs1629816 GG was associated with an increased risk for NHL in our sample (p= 0.0003, OR 1.82; CI: 1.31-2.54). None of the investigated SNPs were associated with obesity, nor was obesity found to be associated with the risk for NHL. CONCLUSIONS: Our study demonstrates an association between rs1629816, a SNP in the GHRL regulatory region, and NHL in Kuwaitis.

Association of Genetic Polymorphisms in the VKORC1 and CYP2C9 Genes with Warfarin Dosage in a Group of Kuwaiti Individuals.

BACKGROUND AND OBJECTIVE: Warfarin is the most widely prescribed oral anticoagulant worldwide. The narrow therapeutic index and the large variation in the inter-individual dose of warfarin are problematic, since the side effects can be lethal. Single nucleotide polymorphisms (SNP) in CYP2C9 and VKORC1 have been shown to significantly affect warfarin dosage toleration and this effect varies among different populations. We aimed to investigate the effect of these SNPs on warfarin dosage in a sample of Kuwaiti patients. METHODS: Kuwaiti patients who were taking a maintenance dose of warfarin were genotyped for CYP2C9*1, *2 and *3 and VKORC1 rs9923231, rs9934438, rs7294 and rs2884737. The association of these SNPs with the warfarin dose was evaluated. RESULTS: For CYP2C9, the CYP2C9 *1/*1 genotype required a higher dose (5.5 ± 3.3 mg/day) compared to non-*1/*1 (3.3 ± 1.7 mg/day) (p = 0.003). For VKORC1, the daily warfarin dose was significantly different (p = 0.001) among the three genotypes of rs9923231, rs9934438 and rs2884737, with carriers of the wild-type genotype requiring the highest dose compared to variant allele carriers (p ≤ 0.001-0.002). There was no association found between the daily warfarin dose and the rs7294 polymorphism. CONCLUSIONS: Our data showed that individuals carrying the wild-type allele of CYP2C9 or VKORC1 rs9923231, rs9934438 or rs2884737 are less sensitive than individuals with the variant alleles of these SNPs and therefore required a higher daily maintenance dose of warfarin. Our study confirms the association between SNPs in CYP2C9 and VKORC1 and warfarin dose tolerance in Kuwaiti patients.