Assessment of South Asian Pediatric Acute Kidney Injury: Epidemiology and Risk Factors (ASPIRE)-a prospective study on "severe dialysis dependent pediatric AKI".

BACKGROUND: Pediatric acute kidney injury (AKI) is a global health concern with an associated mortality risk disproportionately pronounced in resource-limited settings. There is a pertinent need to understand the epidemiology of pediatric AKI in vulnerable populations. Here, we proposed a prospective study to investigate the epidemiology and associated risk factors of "severe dialysis dependent AKI" in children among South Asian nations which would be the first and largest of its kind. METHODS: The ASPIRE study (part of PCRRT-ICONIC Foundation initiative) is a multi-center, prospective observational study conducted in South Asian countries. All children and adolescents ≤ 18 years of age who required dialysis for AKI in any of the collaborating medical centers were enrolled. Data collection was performed until one of the following endpoints was observed: (1) discharge, (2) death, and (3) discharge against medical advice. RESULTS: From 2019 to 2022, a total of 308 children with severe AKI were enrolled. The mean age was 6.17 years (63% males). Secondary AKI was more prevalent than primary AKI (67.2%), which predominantly occurred due to infections, dehydration, and nephrotoxins. Common causes of primary AKI were glomerulonephritis, hemolytic uremic syndrome, lupus nephritis, and obstructive uropathy. Shock, need for ventilation, and coagulopathy were commonly seen in children with severe AKI who needed dialysis. The foremost kidney replacement therapy used was peritoneal dialysis (60.7%). The mortality rate was 32.1%. CONCLUSIONS: Common causes of AKI in children in South Asia are preventable. Mortality is high among these children suffering from "severe dialysis dependent AKI." Targeted interventions to prevent and identify AKI early and initiate supportive care in less-resourced nations are needed.

Multicenter study on the genetics of glomerular diseases among southeast and south Asians: Deciphering Diversities - Renal Asian Genetics Network (DRAGoN).

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

Frequency of Her2/neu expression in colorectal adenocarcinoma: a study from developing South Asian Country.

BACKGROUND: Human Epidermal Growth Factor (Her-2/neu) has strong therapeutic implications in certain cancers like breast and gastric cancer. Literature on its frequency in colorectal cancer is scarce. In this study, we have investigated the frequency of Her-2/neu expression in colorectal adenocarcinomas and its association with various clinicopathological variables. METHODS: A total of 95 patients who underwent colonoscopic biopsy or colectomy were studied after Institutional Ethical Approval. Hematoxylin & eosin (H&E) staining was performed on all the tissue sections. Expression of Her-2/neu was investigated by immunohistochemistry using α-Her-2 antibody. In order to quantify Her-2/neu expression, three criterias were applied that includes the pattern of staining, intensity of staining and percentage of tumor cells stained. Furthermore, its association was seen with various clinicopathological variables including age, gender, histopathological type, grade and stage of the tumor. Data was entered and analyzed using SPSS version 21. A p-value of < 0.05 was considered as significant. RESULTS: From the total of 95 cases, 75 (78.9 %) cases showed Her-2/neu expression. Pattern of Her-2/neu staining was significantly associated with the grade of colorectal cancer depicting cytoplasmic Her-2/neu expression higher in low grade (50 %) while membranous Her-2/neu expression more in high grade colorectal cancer (45 %) (P-value = 0.030). Pattern of Her-2/neu staining was also significantly associated with the type of colorectal cancer representing membranous Her-2/neu expression to be more common in mucinous type (38.5 %) while cytoplasmic Her-2/neu expression to be more frequent in non mucinous type (42.7 %) of colorectal cancer (p-value = 0.024). We observed a significant association between percentage of cells stained & tumor type, with score 3+ maximum in non mucinous type of colorectal cancer (p-value = 0.006). CONCLUSION: Her2/neu is considerably expressed in colorectal adenocarcinoma in Pakistani population. Our findings indicate a significant strong association of cytoplasmic Her-2/neu expression with low grades and membranous Her-2/neu expression with high grades of colorectal cancer. These findings add to the body of information & may help in conducting clinical trials in future to explore its therapeutic significance as well.

Effect of Intense Pulsed Light versus Intradermal Tranexamic Acid for the Management of Melasma.

OBJECTIVE: To compare the effectiveness of intense pulsed light (IPL) and intradermal tranexamic acid (TXA) in treating melasma. STUDY DESIGN: A cross-sectional analytical study. Place and Duration of the Study: Department of Dermatology, Dow International Medical College, Dow University Hospital, Karachi, Pakistan, from 15th January to 15th July 2023. METHODOLOGY: A total of 62 patients with melasma, aged 20-50 years, were divided into two groups. Group A (32 patients) received IPL (560 nm filter was used) treatment, and Group B (30 patients) received intradermal TXA. Each group underwent four treatment sessions with varying intervals. Melasma area and severity index (MASI) scores were used to compare the effects of treatment. RESULTS: After a 3-month treatment period, both groups showed reduced mMASI scores compared to baseline with a significant initial difference between Group A (8.6 ± 4.2) and Group B (5.4 ± 2.7, p <0.001). However, post-treatment, there was no significant difference in mMASI scores (Group A: 3.8 ± 2.6; Group B: 3.2 ± 2.0, p = 0.29). IPL treatment (Group A) demonstrated a significant reduction in mMASI scores (57.1 ± 19.7) compared to intradermal TXA treatment (Group B, 42.2 ± 18.8, p = 0.0034). CONCLUSION: Both IPL and intradermal TXA treatments effectively reduced melasma, with IPL exhibiting superior results. However, post-treatment outcomes converged, emphasising the need for personalised approaches considering the unique characteristics of South East Asian skin. KEY WORDS: Intense pulsed light, Melasma, Intradermal tranexamic acid.

Isotretinoin's Effect on Fasting Lipid Profile in Acne Patients.

OBJECTIVE: To determine the isotretinoin's effect on fasting lipid profile in patients with acne. STUDY DESIGN: Observational study. Place and Duration of the Study: Outpatient Department of Dermatology, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan, from 22nd June to 21st December 2022. METHODOLOGY: Patients of clinically moderate and severe acne were selected and prescribed a dose of 0.5mg /kg cap isotretinoin for 6 months. They were advised to get a fasting lipid profile at the baseline and then after two months of isotretinoin therapy. National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 grading system and Adult Treatment Panel III were used for the grading of abnormalities. McNemar Bowker test was used to assess the difference in variables [serum triglycerides (TGs), cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL)] at the baseline and after 2 months follow-up. RESULTS: A total of 214 patients were evaluated. After 2 months of isotretinoin therapy, TGs and cholesterol levels were elevated to higher grade in 2% of the patients. Likewise in 1% of patients, LDL levels rised to higher grade. Moreover, HDL levels declined to lower grade in 2% of the patients taking isotretinoin. CONCLUSION: Insignificant alterations in the various serum lipid parameters were observed in acne patients during isotretinoin therapy. It is advisable to obtain a baseline fasting lipid profile in all acne patients on isotretinoin and repeated in those with baseline abnormal levels and in patients with a clinical sign of metabolic syndrome and a family history of dyslipidemias. KEY WORDS: Acne, Hyperlipidemias, Isotretinoin, Laboratory monitoring.

Psoralen-ultraviolet A treatment with Psoralen-ultraviolet B therapy in the treatment of psoriasis.

OBJECTIVE: To compare the conventional psoralen-ultraviolet A treatment with psoralen-ultraviolet B therapy in the treatment of psoriasis. METHODOLOGY: We studied 50 patients of plaque type psoriasis who were selected to receive either conventional psoralen-ultraviolet A or psoralen-ultraviolet B treatment. RESULTS: There was no significant difference between the two treatment groups in the number of patients whose skin cleared of psoriasis or the number of exposures required for clearance. Profile of side effects and disease status was also similar after three months of follow up. CONCLUSION: Psoralen-ultraviolet B treatment is as effective as conventional psoralen-ultraviolet A in the treatment of psoriasis. Further long term studies are needed to assess the safety of psoralen-ultraviolet B.

Membranoproliferative Glomerulonephritis Type I Associated with Intravenous Immunoglobulin Administration Arising in a Child with X-Linked Agammaglobulinemia: A Case Report and a Reappraisal.

In 1952, X-linked agammaglobulinemia (XLA) was discovered as a rare inherited disorder. It markedly compromises the ability of the body to combat infectious microorganisms. Membranoproliferative glomerulonephritis (MPGN) Type I is characterized by subendothelial immune complex deposits. Patients with XLA can rarely develop immune-complex-induced diseases. Here, we report a case of MPGN Type I in a 12-year-old male patient with a past and family history of XLA. The patient presented with fever, productive cough, vomiting, and lower limb edema. Clinical and radiological examinations established a diagnosis of bronchopneumonia. The laboratory findings revealed proteinuria and hematuria, and a renal biopsy was performed. The histological examination of this biopsy revealed mesangial hypercellularity and thickened basement membranes. Immunofluorescence studies showed mesangiocapillary staining for Complement 3 and Immunoglobulin (Ig) G and, to a lesser extent, for IgA, IgM, and Complement 1q. Ultrastructural studies revealed partly thick, double-contoured glomerular basement membranes, glomerular endothelial cells with swollen cell bodies, and podocytes with effaced foot processes. Small subendothelial and mesangial eosinophilic deposits were identified. The diagnosis of MPGN type I was established. The patient was started on prednisolone. To the best of our knowledge, this is a rare case of MPGN Type I in a patient with XLA. The pathogenetic mechanisms underlying the development of MPGN Type I were not apparent in our patient. However, residual humoral immunity may play a role in the development of MPGN.

Association of Vitamin D with Moderate to Severe Acne Vulgaris.

OBJECTIVE: To determine the association of vitamin D deficiency in moderate to severe acne. STUDY DESIGN: A comparative study. Place and Duration of the Study: Dermatology OPD at Dow University of Health Sciences, Karachi, Pakistan, from December 2021 to May 2022. METHODOLOGY: Fifty patients with moderate acne, 50 patients with severe acne, and 50 healthy controls were inducted. Information regarding age, gender, and medical and medication history were taken. The severity of acne was rated according to the GAGS (global acne grading system) score. Levels of 25(OH) D were classified as sufficient (>20 ng/mL), insufficient (12-20 ng/mL), or deficient (<12 ng/mL). Significance was taken at p-value <0.05. RESULTS: The median concentration of vitamin D levels was 7.09 ng/ml in severe acne vulgaris, 13.7 ng/ml in moderate acne vulgaris and 21.6ng/ml in the control group. Serum vitamin D levels were significantly lower (p<0.001) in individuals with acne vulgaris as compared to the healthy controls. However, the decrease in level of vitamin D did not correspond with the severity of acne vulgaris. CONCLUSION: Vitamin D deficiency is additionally pronounced in acne vulgaris individuals, but vitamin D levels are not proportional to the severity of acne vulgaris. KEY WORDS: Acne vulgaris, Vitamin D deficiency, Pilosebaceous unit, GAGS score.

Parenteral iron sucrose in iron deficiency anaemia of paediatric chronic kidney disease.

BACKGROUND: Erythropoietin (Epo) and iron therapy plays a major role in the management of renal anaemia. Iron sucrose (IS) has been used to treat iron deficiency anaemia (IDA) and to maintain adequate iron store in chronic kidney disease (CKD). The objective of the study was to determine the response and safety of IS in the treatment of IDA. METHODS: This retrospective study was carried out in the Department of Nephrology, National Institute of Child Health, Karachi from Dec 2008 to Dec 2010. Children aged 6 months to 14 years, CKD-stage 2-5, and IDA were included. Pertinent data including age, gender, serum creatinine (SCr), CKD-stage, aetiology, treatment mode, IS dose, pre- and posttreatment parameters and side effects were collected and analysed. RESULTS: Among 35, majority (66%) were boys. Mean age was 6.97 +/- 4.13 years and mean SCr was 3.78 +/- 3.1 mg/dl. Majority were in CKD-stage 4-5 and treated conservatively. Major aetiologies were hypoplasia-dysplasia (40%), juvenile nephronophthiasis (17.14%), posterior urethral valves, and stones. Baseline mean Hb and Transferrin Saturation (TS) was 7.38 +/- 1.38 g/dl and 11.19 +/- 5.28% respectively. Mean Hb increased to 9.22 +/- 16.32 g/dl with correction of iron deficit (p<0.001) and a sustained rise in Hb was observed after Epo and maintenance iron sucrose. Mean TS% increased to 49.13 +/- 18% (p<0.001). No major side effects were observed except iron overload. CONCLUSION: Iron sucrose was effective in improving IDA in CKD without significant side effects. Iron sucrose may be used to treat IDA with monitoring for iron overload.

Pediatric Continuous Renal Replacement Therapy (PCRRT) expert committee recommendation on prescribing prolonged intermittent renal replacement therapy (PIRRT) in critically ill children.

INTRODUCTION: Recently, prolonged intermittent renal replacement therapies (PIRRT) have emerged as cost-effective alternatives to conventional CRRT and their use in the pediatric population has started to become more prominent. However, there is a lack of consensus guidelines on the use of PIRRT in pediatric patients in an intensive care setting. METHODS: A literature search was performed on PubMed/Medline, Embase, and Google Scholar in conjunction with medical librarians from both India and the Cleveland Clinic hospital system to find relevant articles. The Pediatric Continuous Renal Replacement Therapy workgroup analyzed all articles for relevancy, proposed recommendations, and graded each recommendation for their strength of evidence. RESULTS: Of the 60 studies eligible for review, the workgroup considered data from 37 studies to formulate guidelines for the use of PIRRT in children. The guidelines focused on the definition, indications, machines, and prescription of PIRRT. CONCLUSION: Although the literature on the use of PIRRT in children is limited, the current studies give credence to their benefits and these expert recommendations are a valuable first step in the continued study of PIRRT in the pediatric population.