Patterns of suicide in Kuwait from 2014 to 2018.

OBJECTIVES: Suicide is a public health problem in many countries around the world and is one of the top ten causes of death internationally. We performed a retrospective study from 2014 to 2018 to study the patterns of suicide in Kuwait. STUDY DESIGN: After reviewing files from the General department of Criminal Evidence, we collected a total of 297 in our study period that were signed out as suicide fatalities. METHODS: The relationship between demographic factors (e.g. age, sex, residential area) and suicides were studied using various statistical methodologies. RESULTS: The majority of the 297 samples were in the age range of 19-35 years (180; 60.6%) and 36-65 years (107; 36%). Males constituted the majority of cases (241; 81.1%). The sample consisted of 20 different nationalities. More than half of the 297 samples were Indian (179; 60.2%), whereas Kuwaitis were a minority (22; 7.4%). Hanging was the preferred method of suicide in our study population (269; 90.6%). The governorate of Ahmadi had the highest death toll (89; 30%), followed by Farwaniyah (77; 25.9%) and Jahra (64; 21.5%). CONCLUSION: The government of the State of Kuwait needs to target the group that has the largest number of fatalities by increasing education and awareness of employers and employees to the danger of this condition and the driving factors that lead people to it.

Chest wall lymphomas: Fine needle aspiration cytodiagnosis and review of the literature.

OBJECTIVE: Compared to other chest wall malignancies, lymphoma is a common disease. However, published literature on a series of lymphoma cases involving the chest wall is scarce. The aim of the present study, was to describe experience with chest wall swellings diagnosed as lymphoid neoplasms on fine needle aspiration (FNA) cytology. METHODS: Eleven chest wall swellings were diagnosed as lymphoid neoplasms on FNA over a period of 15 years (January 2000-December 2014). The age of patients ranged from 19 to 73 years (median, 46). The male-to -emale ratio was 7:4. Ten cases had an anterior or lateral chest wall mass, and one swelling was in the scapular region. Six cases had concurrent lymphadenopathy, and one had bone involvement. The FNA smears were reviewed and classified under WHO Classification of Hematopoietic Neoplasms. The histopathological diagnoses were available in eight cases. RESULTS: The preliminary cytodiagnoses in 11 cases of chest wall lymphoid neoplasms were anaplastic large cell lymphoma (ALCL) in two cases, and ALCL/malignant melanoma, ALCL/T-cell-rich-B-cell lymphoma (TCRBCL)/Hodgkin's lymphoma (HL), plasmacytoma/neuroendocrine carcinoma, Hodgkin's lymphoma, small cell NHL/CLL, NHL, suggestive of NHL, post-transplant peripheral T-cell lymphoma (PTCL), and a malignant plasma cell tumour in one case each. The reviewed cytodiagnoses of lymphoid neoplasms were as follows: ALCL ( five cases), centroblastic lymphoma (two cases), and small cell lymphoma/CLL, post-transplant peripheral T-cell lymphoma, Hodgkin's lymphoma and plasmacytoma (one case each). Histopathological diagnoses available in eight cases confirmed the presence of lymphoid neoplasms. CONCLUSION: A variety of lymphoid neoplasms involved the chest wall, and among them, ALCL was a common form.

Evaluation of associations between single nucleotide polymorphisms in the FRMD3 and CARS genes and diabetic nephropathy in a Kuwaiti population.

Diabetic nephropathy is the leading cause of end-stage kidney disease in the world. Many single nucleotide polymorphisms (SNPs) have been associated with diabetic nephropathy. SNPs at the 4.1 protein ezrin, radixin, moesin domain 3 (FRMD3) and cysteinyl t-RNA synthetase (CARS) genes have a well-established relationship with diabetic nephropathy. However, this association has not been evaluated in a Kuwaiti population. DNA was extracted from blood samples obtained from patients with diabetic nephropathy (N = 38); the genes of interest were amplified, and the SNPs were genotypes. Diabetics without nephropathy (N = 64) were used as controls. The risk (G and C) and non-risk (C and T) allele frequencies of the SNPs at the rs1888747 and rs739401 loci of FRMD3 and CARS, respectively, did not differ significantly between the diabetics with (case) and without (control) nephropathy (P > 0.05). These findings suggest that the molecular mechanisms involved in diabetic nephropathy may be different in a Kuwaiti population, compared to other populations (such as Japanese and Caucasian Europeans). The discrepancies observed in our study could also be attributed to the smaller sample size analyzed in this study. Therefore, further analyses with larger samples are required to identify the susceptibility genes in a Middle-Eastern population.

Early sirolimus therapy in renal transplant recipients at high risk: is it justified?

BACKGROUND: We studied early sirolimus (SRL) therapy in renal transplant recipients at high risk after administration of antithymocyte globulin or interleukin-2 receptor blockade induction. PATIENTS AND METHODS: In 45 patients, SRL therapy was started within 1 month after transplantation. The primary indications for conversion of treatment from calcineurin inhibitors (CNIs)-mycophenolate mofetil (MMF)-steroid to SRL-MMF-steroid were biopsy-proved rejection (after treatment), CNI toxicity, CNI elimination, and acute tubular necrosis. Pediatric, geriatric, and other patients with medical comorbidities were not excluded. RESULTS: Post-SRL rejection episodes were reported in 22.2% of recipients including 15.6% who were resistant to steroid therapy. Mean (SD) follow-up after SRL therapy was 59.9 (8.1) months. Proteinuria greater than 2 g/d (P = .001), leukopenia (P < .001), hyperlipidemia (P < .001), and transaminases values (P = .02) increased significantly after SRL therapy. Graft survival was 88.8%, and patient survival was 93.3%. There was significant improvement in serum creatinine concentration and estimated creatinine clearance by the end of the study (P < .001). A high incidence of adverse effects and infections was noted post-SRL therapy, and the drug was discontinued in 31% of patients because of multiple adverse effects. At multivariate analysis, age, hypertension, nutritional status, bone marrow suppression, hyperlipidemia, and graft dysfunction were identified as risk factors for worse graft and patient outcome. CONCLUSION: Early treatment with combined SRL-MMF-steroid may be effective as a CNI-free immunosuppression regimen in patients at high risk; however, there is a high rate of adverse effects during long-term follow-up.

Active management of post-renal transplantation BK virus nephropathy: preliminary report.

OBJECTIVE: To assess the efficacy of leflunomide, intravenous immunoglobulins, and ciprofloxacin as active treatment of postrenal transplant BK virus nephropathy (BKVN) in graft outcome at 1 year. PATIENTS AND METHODS: Renal transplant recipients with positive results of 2 BK virus polymerase chain reaction tests of urine and blood underwent graft biopsy to confirm BKVN. If BKVN was diagnosed, antimetabolite therapy (mycophenolate mofetil or azathioprine) was changed to leflunomide therapy accompanied by a course of immunoglobulin and oral ciproflxacin. RESULTS: Of 18 patients evaluated, 72% were men. Nine patients received cadaveric organs, with a mean of 3.6 HLA mismatches. All patients received induction thereapy (61% thymoglobulin), and 61% received antirejection therapy before BKVN was diagnosed. Maintenance immunosuppression therapy was primarily with prednisolone (94%); mycophenolate mofetil, 2 g/d (94%); and tacrolimus (61%). At baseline, mean (SD) creatinine clearance was 35.6 (11.5) mL/min/1.73(2), which decreased to 29.3 (17.3) mL/min/1.73(2) at 1 year (P = .01). Patients were divided into 2 groups of 9 each according to creatinine clearance values. In group 1, baseline value was 44.5 (6.6) mL/min/1.73(2), compared with 25.36 (7.8) mL/min/1.73(2) in group 2, which decreased to 42.66 (12.8) mL/min/1.73(2) (P = .23) and 16.76 (9.0) mL/min/1.73(2) (P = .009), respectively, at 1 year. Three grafts (16.7%) were lost by the end of the study, all in group 2 (P = .03). CONCLUSION: Late diagnosis and intensive immunosuppression predispose to BKVN. Early active treatment of BKVN may improve graft outcome at 1 year posttransplantation.

Long-term follow-up of 100 high-risk renal transplant recipients converted from calcineurin inhibitors to sirolimus: a single center experience.

While conversion of stable renal transplant recipients (RTR) from calcineurin inhibitors (CNI) to sirolimus (SRL) is safe and effective, it is still under investigation for recent, high-risk cases. We studied the long-term effects of conversion of high-risk subjects maintained on a CNI, mycophenolate mofetil, plus steroid regimen to SRL, mycophenolate mofetil, plus steroid on graft and patient outcomes. We retrospectively reviewed the first 100 RTR converted to SRL treatment over approximately 5 years. The main indications for conversion were biopsy-proven acute rejection (BPAR), CNI toxicity, CNI elimination, and acute-tubular necrosis (ATN). Exclusion criteria were limited to bone marrow suppression. The overall mean +/- SD age was 38.5 +/- 15.6 years, including pediatric and geriatric age groups. Mean +/- SD body mass index (BMI) was 28.99 +/- 8.0 and 40% had a BMI > 30. There were 40% RTR from deceased donors and 60% showed 4 to 6 HLA mismatches. Preconversion total BPAR and steroid-resistant rejection incidences were 35% and 14%, respectively. Mean +/- SD time to start of SRL was 11.9 +/- 22.8 months posttransplantation. Proteinuria > 2 g/d, leukopenia, and hyperlipidemia increased significantly after conversion (P = .001, P = .0003, and P = .0001, respectively). Patient and graft survivals were 95% and 90%, respectively. There was significant improvement in graft function postconversion (P < .0001). There was a high incidence of side effects and cases of SRL discontinuation. Multivariate analysis demonstrated the influence of bone marrow suppression, obesity, hyperlipidemia, nutritional status, proteinuria, and graft function on graft and patient outcomes. We concluded that conversion from CNI to SRL was effective among high-risk RTR, but with a high incidence of adverse events during long-term follow-up.

Mice with altered alpha-actinin-4 expression have distinct morphologic patterns of glomerular disease.

Mutations in ACTN4, encoding the actin-binding protein alpha-actinin-4, cause a form of familial focal segmental glomerulosclerosis. We had developed two strains of transgenic mice with distinct alterations in the expression of alpha-actinin-4. One strain carried a human disease-associated mutation in murine Actn4, whereas the other knockout strain did not express alpha-actinin-4 protein. Most adult homozygous Actn4 mutant and knockout mice developed collapsing glomerulopathy. Homozygous Actn4 mutant mice also exhibited actin and alpha-actinin-4-containing electron-dense cytoplasmic structures, that were present but less prominent in heterozygous Actn4 mutant mice and not consistently seen in wild-type or knockout mice. Heterozygous Actn4 mutant mice did not develop glomerulosclerosis, but did exhibit focal glomerular hypertrophy and mild glomerular ultrastructural changes. The ultrastructural abnormalities seen in heterozygous Actn4 mutant mice suggest low-level glomerular damage, which may increase susceptibility to injury caused by genetic or environmental stressors. Our studies show that different genetic defects in the same protein produce a spectrum of glomerular morphologic lesions depending on the specific combination of normal and/or defective alleles.

Gastrointestinal stromal tumors: clinicopathological and immunohistochemical features.

OBJECTIVES: To study the clinicopathological and immunohistochemical features of gastrointestinal stromal tumors (GISTs) in Kuwait. MATERIALS AND METHODS: Hematoxylin- and eosin-stained sections of primary gastrointestinal mesenchymal tumors were reviewed. Immunohistochemical staining was performed using a panel of antibodies to determine muscle and neural differentiation, the incidence of CD117 and CD34 expression, as well as bcl-2 and cytokeratin expression. Each stain was interpreted as negative or positive. The staining intensity of positive cases was graded as weak, moderate or strong. RESULTS: The age range was 25-80 with an average age of 54 and a male:female ratio of 3:2. The stomach was the most common site for these tumors, followed by the small intestine. Histologically, 46% were classified as malignant and 54% were benign. Most of the malignant tumors occurred in males, particularly in the stomach or small intestine. There was no significant difference in patient age between malignant and benign tumors. The most sensitive markers were muscle-specific actin for muscle differentiation and glial fibrillary acidic protein for neural differentiation. CD117 expression was seen in 81% and CD34 in 54% of all tumors. CONCLUSIONS: The results of this study show that the stomach is the most common site for these tumors, that malignant tumors are more likely to occur in the small intestine than in the stomach, and that there is no difference between benign and malignant tumors with regard to age. Our findings are comparable to those of other workers, although our male:female ratio was slightly higher.

Basidiobolus ranarum as an etiologic agent of gastrointestinal zygomycosis.

Basidiobolus ranarum is a known cause of subcutaneous zygomycosis. Recently, its etiologic role in gastrointestinal infections has been increasingly recognized. While the clinical presentation of the subcutaneous disease is quite characteristic and the disease is easy to diagnose, gastrointestinal basidiobolomycosis poses diagnostic difficulties; its clinical presentation is nonspecific, there are no identifiable risk factors, and all age groups are susceptible. The case of gastrointestinal basidiobolomycosis described in the present report occurred in a 41-year-old Indian male who had a history of repair of a left inguinal hernia 2 years earlier and who is native to the southern part of India, where the subcutaneous form of the disease is indigenous. Diagnosis is based on the isolation of B. ranarum from cultures of urine and demonstration of broad, sparsely septate hyphal elements in histopathologic sections of the colon, with characteristic eosinophilic infiltration and the Splendore-Hoeppli phenomenon. The titers of both immunoglobulin G (IgG) and IgM antibodies to locally produced antigen of the fungus were elevated. The patient failed to respond to 8 weeks of amphotericin B therapy, and the isolate was later found to be resistant to amphotericin B, itraconazole, fluconazole, and flucytosine but susceptible to ketoconazole and miconazole. One other noteworthy feature of the fungus was that the patient's serum showed raised levels of Th2-type cytokines (interleukins 4 and 10) and tumor necrosis factor alpha. The present report underscores the need to consider gastrointestinal basidiobolomycosis in the differential diagnosis of inflammatory bowel diseases and suggests that, perhaps, more time should be invested in developing standardized serologic reagents that can be used as part of a less invasive means of diagnosis of the disease.