Improving Surgical Safety in Living Donor Renal Transplantation With Antiseptic Skin Preparation, Bladder Irrigation, Corner-Saving Vascular Anastomosis, DJ Stenting, and Extravesical Ureteroneocystostomy Modifications: A Comprehensive Approach.

Introduction The antiseptic skin preparation, bladder irrigation, corner-saving vascular anastomosis, DJ stenting, and extravesical ureteroneocystostomy (ABCDE) approach encompasses a range of modifications applied during different stages of the surgical procedure in renal transplantation. These modifications include the following: A, antiseptic skin preparation sequentially with cetrimide 3.35%, chlorhexidine scrub 4%, spirit, and povidone-iodine 10%; B, bladder irrigation with amikacin and betadine solution; C, corner-saving end-to-side vascular anastomosis; D, DJ stenting with early postoperative removal within three weeks; and E, extravesical ureteroneocystostomy using our institute's modified Lich-Gregoir technique. Methods This prospective observational study was conducted at our institution between March 2021 and May 2023. Data were collected from the patients' medical records and analyzed using Statistical Package for the Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY, USA). Statistical tests, including t-test, Mann-Whitney test, chi-square test, and Fisher's exact test, were used for analysis. The study assessed various recipient, donor, intraoperative, and post-transplant factors, as well as surgical complications and stent-related factors. Results Out of 72 renal transplantations, 12 (16.6%) had the following surgical complications: urinary (n = 4; 5.5%), wound-related (n = 3; 4.1%), and lymphocele (n = 5; 6.9%). The most common complications were lymphocele (n = 5; 6.9%) and urinary leak (n = 4; 5.5%). Surgical complications were more common in male recipients (91.6% versus 8.3%), as well as in recipients with longer dialysis duration (24 ± 17 versus 11.0 ± 7 months) and had extended hospitalization time (16.4 ± 8.6 versus 8.0 ± 2.9 days) (p < 0.05). Wound infection correlated with longer surgeries (>300 minutes) and other complications. Lymphocele patients had higher drain output (>500 mL) on day 1 and longer hospital stays (>15 days). Urinary tract infections (UTIs) were linked to dialysis duration (>24 months), diabetes, and longer indwelling times of DJ stents and urinary catheters. Early DJ stent removal (<3 weeks) reduced UTI incidence and symptoms (p < 0.05). All complications were categorized as minor (3a or less), according to the Clavien-Dindo classification. Conclusion The modified ABCDE surgical approach in renal transplantation decreased the complications, showing favorable outcomes compared to those in the literature.

A significant association of the CTLA4 gene variants with the risk of autoimmune Graves' disease in ethnic Kashmiri population.

Graves' disease (GD) is the commonest cause of hyperthyroidism in populations with adequate iodine intake. It results from an abnormality in the immune system, which produces unique antibodies causing over production of thyroid hormones and glandular hyperplasia in individuals with genetic susceptibility. The Cytotoxic Lymphocyte Associated Antigen-4 (CTLA4) gene product serves the important function of immunomodulation, thereby helping in maintenance of peripheral self-tolerance. Studies on the association of the CTLA4 SNPs with GD have shown variations in the results from different populations. Since no such study has been carried out in ethnic Kashmiri population, we aimed to study a possible association of the CTLA4 SNPs (+49 A/G, -318C/T, CT 60 A/G and -1661 A/G) with GD. A total of 285 individuals (135 patients with GD and 150 healthy individuals) were genotyped using PCR-RFLP method and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for + 49 A/G SNP (p=<0.001; OR = 5.14; CI = 2.17-12.19) and CT 60 A/G SNP (p = < 0.001; OR = 6.9; CI = 2.8-16.6), while -318C/T and -1661 A/G SNPs showed no significant association. We also studied the mRNA expression of the CTLA4 in patients with GD and healthy individuals by Real-Time PCR and found a decreased expression of the CTLA4 mRNA in PBMCs of patients with GD as compared to healthy controls with a -3.71-fold change. We conclude that the CTLA4 + 49 A/G and CT 60 A/G SNPs have a significant association with the risk of GD development in Kashmiri population and CTLA4 mRNA expression is significantly decreased in GD.

PTPN22 1858 C/T Exon Polymorphism is not Associated with Graves' Disease in Kashmiri population.

BACKGROUND: Graves' disease (GD) is a multifactorial autoimmune disease with contribution from both genetic and epigenetic factors in its causation. Association of genetic factors and GD has been extensively studied. Gene "protein tyrosine phosphatase nonreceptor 22" (PTPN22) is an important immunoregulatory gene preventing hyper responsiveness of T cells by negatively regulating their signal transduction. Association of single-nucleotide polymorphism (SNP) 1858 C/T within PTPN22 with some autoimmune diseases has been described. METHODS: We aimed to analyze whether 1858 C/T SNP of PTPN22 gene has any association with GD in Kashmiri population. Polymerase chain reaction-restriction fragment length polymorphism was performed for genotyping 1858 C/T SNP in 135 patients with GD and 150 age- and gender-matched healthy controls. RESULTS: Among the patients with GD, the frequencies of PTPN22 1858 CC, CT, and TT genotypes were 97.7, 2.2, and 0%, respectively, whereas in healthy controls the frequencies of CC, CT genotypes were 100 and 0%, respectively. No significant association was found between PTPN22 1858 C/T SNP and patients with GD. CONCLUSION: GD is not associated with PTPN22 1858 C/T SNP in Kashmiri population. Furthermore, 1858 C/T SNP in PTPN22 gene could be a part of variation in different ethnic populations across the globe.

Association of FoxP3 promoter polymorphisms with the risk of Graves' disease in ethnic Kashmiri population.

Graves' disease is a multifactorial autoimmune disorder of the thyroid gland, with some extra-thyroidal complications like eye and skin abnormalities in some patients. GD is more prevalent in women than men and is the leading cause of hyperthyroidism worldwide. A complex interaction between genetic and environmental factors is the proposed cause which triggers immune system to produce autoantibodies stimulating the TSH receptor, leading to clinical manifestations such as hyperthyroidism, diffuse thyroid enlargement (goiter) and often ophthalmopathy in affected individuals. Various Single nucleotide gene polymorphisms (SNPs) have been associated with the risk of GD development including promoter SNPs in Forkhead Box P3 (FOXP3). FOXP3 is an important regulatory factor for T cell development and differentiation and therefore has a prominent role in suppression of autoimmune reactions which may lead to predisposition of GD. There have been some studies on the association of FOXP3 SNPs with GD, but no such investigation has been carried out in ethnic Kashmiri population. So, we aimed to study a possible association of FOXP3 promoter SNPs (-3279C/A, -2383C/T & -3499 A/G) with GD. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to genotype 285 individuals (135 GD cases and 150 healthy controls) and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for -3279C/A SNP [OR, 3.48; 95% CI (2.05-5.92); P < 0.001] and -2383C/T SNP [OR, 5.62; 95% CI (2.43-13.00); P < 0.001], while no significant association was seen in case of -3499 A/G SNP. We conclude that -3279C/A and -2383C/T SNPs have a highly significant association with the risk of GD development in Kashmiri population.

Association of polymorphic variants of IL-1ß and IL-1RN genes in the development of Graves' disease in Kashmiri population (North India).

PURPOSE: Graves' disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1ß has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1ß gene promoter region (-511 T>C) (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population. METHODS: A total of 135 Graves' disease patients and 150 healthy individuals were included in the study. PCR and PCR-based restriction analysis methods were done for IL-1RNVNTR and IL-1ß gene polymorphisms respectively. RESULTS: We found statistically significant increased frequencies of the C/C + CT genotype (P = 0.001; odds ratio (OR) = 5.04, 95% confidence interval (CI) = 3.02-8.42) and the C allele (P = 0.001; OR = 3.10, 95% CI = 2.14-4.50) in IL-1ß gene promoter polymorphism (rs16944) with GD patients compared to normal controls. Also in the exon 5 (rs1143634), a significant increase in frequency of the C/C homozygous genotype (P = 0.001; OR = 0.18, 95% CI = 0.11-0.30) and C allele (P = 0.001; OR = 0.31, 95% CI = 0.20-0.48) was observed in GD cases as against controls. For IL-1RNVNTR (rs2234663), we didn't observe any significant difference in the allelic and genotypic frequencies between cases and controls. CONCLUSION: Our findings suggest that both promoter and exon polymorphisms of IL-1ß gene have a significant role in the risk of developing GD, whereas IL-1RNVNTR has no association with GD.