Biallelic variants in CHST3 cause Spondyloepiphyseal dysplasia with joint dislocations in three Pakistani kindreds.

BACKGROUND: Skeletal dysplasia is a heterogeneous group of disorders. Spondyloepiphyseal dysplasias comprise one subgroup. Deficiency of carbohydrate sulfotransferase 3 has been reported in a small number of patients with recessively inherited spondyloepiphyseal dysplasia with joint dislocation, short stature and scoliosis. We report here molecular and clinical findings of affected individuals in three consanguineous Pakistani families. Affected individuals in all three families had a uniform phenotype including severe short stature, multiple dislocated joints, progressive scoliosis and facial dysmorphism. METHODS: Clinical evaluation was done for three unrelated families. Radiological survey of bones was completed for patients from two of the families. Whole exome sequencing index patients from each family was performed followed by Sanger sequencing for validation of segregation of identified variants in respective families. In-silico analysis for determining pathogenicity of identified variants and conservation was done. RESULTS: Whole-exome sequencing revealed biallelic variants c.590 T > C;p.(Leu197Pro), c.603C > A;p.(Tyr201Ter) and c.661C > T;p.(Arg221Cys) in CHST3 (NM_004273.5) in the three families with eight, five and two affected individuals, respectively. Contrary to previous reports, affected individuals in none of the families exhibited a hearing loss. CONCLUSION: We describe genotypic and phenotypic findings of three unrelated families with spondyloepiphyseal dysplasia. Our study confirms phenotypic variability and adds to the genotypic spectrum of spondyloepiphyseal dysplasia.

Ureteral trauma during open surgery: aetiology, presentation and management.

BACKGROUND: Ureteric injury during a surgical procedure is a serious complication with significant morbidity. The objective of this research was to study the aetiology, clinical features and management of iatrogenic ureteric injuries after open surgical procedures. METHODS: This descriptive study was carried out in the Urology and Transplant unit of Institute of Kidney Diseases, Peshawar, from 1st August 2008 to 30th April 2011. Patients with clinical diagnosis of ureteral trauma due to open surgical procedures were included in the study through convenient sampling after informed consent. Important variables under study were: aetiology of ureteric injury, presenting features, time from injury to diagnosis, type of ureteric injury, treatment options, and outcome of treatment. Follow up was at 1, 3, 6 and 12 months. RESULTS: The study included 43 patients; 33 (76.7%) were females and 10 (23.3%) males. Abdominal hysterectomy was the commonest cause 20 (46.5%) of ureteric injury. Common presenting features were urinary incontinence 13 (30.23%), flank pain 7 (16.3%) and anuria 10 (23.3%). Median time from ureteric injury to urological referral was 10 days. Distal ureter was most commonly injured. Percutaneous nephrostomy was carried out in 14 (32.5%) cases. Ureteroscopic ureteric stenting was successful in 5 (11.6%) cases. Ureteroneocystostomy was carried out 25 (58%) cases. Two (4.7%) cases presented very late with non-functioning kidneys and required nephrectomy. Patients developing ureteric stricture after ureteroneocystostomy were managed successfully by endo-urological procedures. Renal function remained stable in all the patients during follow-up and there was no mortality. CONCLUSION: Timely recognition of ureteric injury and its management is associated with good outcome and decreased morbidity.

Effect of Vitamin D Supplementation on the Hemoglobin Level in Chronic Kidney Disease Patients on Hemodialysis: A Systematic Review and Meta-Analysis.

The objective of this study was to evaluate the impact of vitamin D supplementation on hemoglobin levels (Hb) in patients with chronic kidney disease (CKD) undergoing hemodialysis. A systematic search was conducted in electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to April 21, 2023. Inclusion criteria were applied to select relevant studies. Statistical analyses were performed using Review Manager 5.4.1. A random-effects model was used to address heterogeneity, and the mean difference (MD) with the corresponding 95% confidence interval (CI) was reported. Ten studies were included in the analysis, comprising seven clinical trials, two randomized clinical trials, and one retrospective observational study. Subgroup analysis was conducted based on the duration of follow-up: 12 weeks, three months, six months, 12 months, 15 months, and 18 months. A significant increase in hemoglobin levels was observed after 12 months (MD = -0.98 [95% CI -1.88, -0.08]; p = 0.03; I2 = 91%) and 18 months (MD = -1.80 [95% CI -2.56, -1.04]; p < 0.00001; I2 = Not applicable). However, there was no statistically significant relationship between vitamin D supplementation and hemoglobin levels at 12 weeks, three months, six months, and 15 months. The pooled analysis demonstrated a significant increase in hemoglobin levels with vitamin D supplementation (MD = -0.61 [95% CI -0.96, -0.26]; p = 0.03; I2 = 60.7%). This analysis highlights the significant role of vitamin D supplementation in improving anemia in patients with CKD undergoing hemodialysis. Vitamin D supplementation was found to significantly increase hemoglobin levels, particularly after 12 months and 18 months of supplementation.

Comparative Analysis of Inhaled Insulin With Other Types in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

To analyze the effect of Inhaled insulin in Type 1 Diabetes Mellitus and compare it with other routes of administration of Insulin. A systemic search was conducted from the following electronic databases: PubMed/Medline, Cochrane Library, and Google Scholar, from inception to 28th January 2022. All statistical analysis was conducted in Review Manager 5.4.1. All studies meeting inclusion criteria were selected. A random-effect model was used to pool the studies, and the result was reported in the Standard Mean Difference (SMD), Mean Difference (MD), and Risk Ratio (RR) with their corresponding 95% Confidence interval (CI). Thirteen randomized control trials were selected for our meta-analysis. Statistically significant results were obtained for comparing change in weight after insulin administration (MD= -1.08 [-1.21, -0.94]; p< 0.00001; I2= 74%). Other factors assessed were found to be non-significant like HbA1c (SMD= 0.03 [-0.80, 0.86]; p= 0.95; I2= 99%), fasting blood sugar (SMD= -0.31 [-1.52, 0.91]; p= 0.62; I2= 99%) and adverse effects (RR= 1.06 [0.97, 1.16]; p= 0.18; I2= 96%). In this systematic review and meta-analysis, we found that inhaled insulin is equally effective as subcutaneously administered insulin in patients with Type 1 Diabetes. The inhaled insulin was found to show less weight gain and fewer hypoglycemic shifts, with a similar effect on the blood glucose level. No significant difference was observed in the incidence of adverse events.

Direct Stenting Versus Balloon Pre-Dilatation In Elective Percutaneous Coronary Intervention.

BACKGROUND: Stents are now deployed in almost 95% of all percutaneous coronary interventions (PCIs). Recent advances in balloon and stent technology has improved the technique of direct stent (DS) strategy, i.e., stent delivery without pre-dilatation instead of conventional stenting (CS), i.e., stent implantation after balloon pre-dilatation with multiple advantages. METHODS: This randomized controlled trial was conducted at the Cardiology. Department, Punjab Institute of Cardiology, Lahore from April to September, 2017. One hundred patients who were being treated by percutaneous coronary intervention (PCI) were enrolled into two Groups e.g., Group I & group II. 50 patients undergoing direct stenting were enrolled in group I and 50 patients undergoing stenting after balloon pre-dilatation were enrolled in group II after randomization. All patients were treated by single type drug eluting or bare metal stents. Chi square test was used for association and t-test for mean difference between two groups in comparison to post dilatation, fluoroscopy time, procedure time, amount of contrast used, procedural success, side branch compromise, slow flow. The p-value of ˂ 0.05 was significant. RESULTS: This study consisted of 76 males and 24 females out of a total count of 100, with the average age of 52.2±0.01 years. Overall, 43 (43%) patients were diabetic and overall, 44 (44%) were hypertensive. Most of the patients 55 (55%) had PCI to LAD. Average fluoroscopy time 4.l±2.5 minutes in Group I was significantly lesser as compared to 6.7±3.8 minute group II (p-value <0.05). The average procedure time was also marginally lesser in Group I, 23.4±11.6 in comparison to the second Group 33.7±14 (p-value <0.05). Side branch compromise was observed in 10 (20%) in the first group as compared to 8 (16%) the second group. CONCLUSIONS: In comparison to stenting preceded by balloon predilatation, direct stenting is a safer and more feasible procedure with respect to radiation exposure, cost and time duration of the procedure.

A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family.

We report on three new patients with spondyloocular syndrome (SOS) in a consanguineous Pakistani family. All three patients present progressive generalized osteoporosis, short stature, recurrent fractures, hearing loss and visual impairments. WES revealed a novel homozygous frameshift variant in exon 11 of XYLT2 (NG 012175.1, NP_071450.2) resulting in loss of evolutionary conserved amino acid sequences (840 - 865/865) at C-terminus p.R840fs∗115. Sanger Sequencing confirmed the presence of the novel homozygous mutation in all three patients while the parents were heterozygous carriers of the mutation, in accordance with an autosomal recessive inheritance pattern. Only nine variants worldwide have previously been reported in XYLT2 in patients with SOS phenotype. These three patients with novel homozygous variant extend the genotypic and phenotypic spectrum of SOS.